WO2025106754A1 - Coronavirus vaccine - Google Patents

Abstract

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

Description

Attorney Docket No.: 2013237-1270 CORONAVIRUS VACCINE Background [_{001] In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China and it became} clear that a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was the underlying cause. The genetic sequence of SARS-CoV-2 became available to the WHO and public (MN908947.3) and the virus was categorized into the betacoronavirus subfamily. By sequence analysis, the phylogenetic tree revealed a closer relationship to severe acute respiratory syndrome (SARS) virus isolates than to another coronavirus infecting humans, namely the Middle East respiratory syndrome (MERS) virus. [_{002] SARS-CoV-2 infections and the resulting disease COVID-19 have since spread globally, affecting a} growing number of countries. On 11 March 2020 the WHO characterized the COVID-19 outbreak as a pandemic. The ongoing pandemic remains a significant challenge to public health and economic stability worldwide. [_{003] The presentation of COVID-19 is generally with cough and fever, with chest radiography showing} ground-glass opacities or patchy shadowing. However, many patients present without fever or radiographic changes, and infections may be asymptomatic which is relevant to controlling transmission. For symptomatic subjects, progression of disease may lead to acute respiratory distress syndrome requiring ventilation and subsequent multi-organ failure and death. Common symptoms in hospitalized patients (in order of highest to lowest frequency) include fever, dry cough, shortness of breath, fatigue, myalgias, nausea/vomiting or diarrhoea, headache, weakness, and rhinorrhoea. Anosmia (loss of smell) or ageusia (loss of taste) may be the sole presenting symptom in approximately 3% of individuals who have COVID-19. [_{004] Since the initial emergence of SARS-CoV-2, the virus has continued to evolve, giving rise to thousands of} new variants. Many of these variants have an increased growth rate and/or an increased ability to evade immune responses as compared to the first strain of SARS-CoV-2 identified. As a result, there have been successive worldwide waves of different variants. Initial SARS-CoV-2 vaccines have shown a diminished efficacy in regard to the new SARS-CoV-2 variants, although they still provide beneficial health effects, including, e.g., a decreased risk of hospitalization and severe disease. Summary [_{005] The present disclosure provides new technologies (e.g., compositions and methods) for inducing an} immune response against a coronavirus (e.g., SARS-CoV-2). [_{006] In some embodiments, the technologies described in the present disclosure can provide significant} advantages as compared to first generation SARS-CoV-2 vaccines (e.g., vaccines that deliver a full length S protein, such as, e.g., LNP-formulated RNA that encodes a full length S protein of a SARS-CoV-2 virus). These advantages can include, e.g., an improved response. An improved immune response can comprise, e.g., increased antibody titers and/or increased neutralizing antibody titers against a SARS-CoV-2 virus as compared to compositions that deliver a full length S protein of a coronavirus. In some embodiments, an improved immune response can include a broader cross neutralization response (i.e., higher neutralizing titers against a range of SARS-CoV-2 viruses) as compared to a composition that delivers a full length S protein. In some embodiments, an improved immune response can include a more robust immune response (e.g., an immune response that results in antibody titers that remain elevated for a longer period of time following vaccination as compared to compositions that deliver a full length S protein of a coronavirus)._{12410924v1 Page 1 of 696} [007] Among other things, the present disclosure provides an insight that the S2 domain of the S protein of a coronavirus comprises a number of conserved neutralizing epitopes. Without wishing to be bound by theory, the conserved nature of these epitopes means that induction of an immune response can result in an immune response that is more broadly cross-neutralizing and/or more durable as compared to compositions that deliver a full length S protein of a coronavirus. The present disclosure, among other things, provides certain insights into the design of S2 antigens that result in an improved immune response.

[008] Among other things, the present disclosure also provides compositions that deliver both an RBD and an S2 polypeptide of a coronavirus protein or one or more fragments of an S2 polypeptide. Among other things, the present disclosure provides a novel antigenic polypeptide design that comprises an S2 domain or one or more fragments thereof and an RBD of a coronavirus. In some embodiments, an RBD and an S2 polypeptide are delivered by an RNA comprising a nucleotide sequence that encodes a polypeptide comprising an RBD and an S2 polypeptide. In some embodiments, the present disclosure provides an immunogenic fragment of an S2 domain and an RBD of a coronavirus.

[009] In some embodiments, the compositions provided herein deliver an immunogenic fragment of the S2 polypeptide. In particular, in some embodiments, compositions described herein deliver a fragment of the S2 comprising the stem helix and/or fusion peptide of an S2 polypeptide. Without wishing to be bound by theory, the present disclosure provides the insight that the stem helix and the fusion peptide of an S2 polypeptide are both highly conserved and also comprise neutralizing epitopes. Thus, by inducing an immune response against a stem helix and/or a fusion peptide, an improved immune response can be generated, including, e.g., improved antibody titers, neutralizing antibody titers, and/or cross-neutralization as compared to RNA encoding a full length S protein. In some embodiments, a polypeptide comprising an immunogenic fragment of the S2 polypeptide is also comprises an RBD of a coronavirus S protein.

[0010] Among other things, the present disclosure provides insights into the design of polypeptides that can provide for improved immune responses. These insights include, e.g., domains to attach to antigenic regions (e.g., secretory signal peptides, transmembrane doamins, and multimerization domains), and design of polypeptides that result in improved immune responses.

[0011] Methods and agents described herein are, in particular, useful for the prevention or treatment of coronavirus infection. Administration of RNA disclosed herein to a subject can protect the subject against coronavirus infection. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen. Administering to the subject RNA encoding vaccine antigen may provide (following expression of the RNA by appropriate target cells) vaccine antigen for inducing an immune response against vaccine antigen (and disease-associated antigen) in the subject.

[0012] Also disclosed herein are compositions that can produce an improved immune response (e.g., an immune response having broader cross-neutralization activity, higher neutralization titers, and/or which is less susceptible to immune escape), e.g., as compared to previously approved vaccines (e.g., previously approved RNA or protein vaccines), vaccines that deliver antigens of a Wuhan S protein, and/or vaccines that deliver antigens of other SARS-CoV-2 variants.

[0013] In some embodiments, the concentration of RNA in a composition described herein (e.g., a pharmaceutical RNA preparation) is about 0.1 mg/ml. In some embodiments, about 30 ug of RNA is administered by administering about 200 uL of RNA preparation. [0014] In some embodiments, RNA in a pharmaceutical RNA preparation is diluted prior to administration (e.g., diluted to a concentration of about 0.05 mg/ml). In some embodiments, administration volumes are between about 200 pl and about 300 pl. In some embodiments, RNA in a pharmaceutical RNA preparation is formulated in about 10 mM Tris buffer, and about 10% sucrose.

[0015] In some embodiments, RNA in a pharmaceutical RNA preparation is present at a concentration of about 0.1 mg/ml, and is formulated in about 10 mM Tris buffer, and about 10% sucrose, and a dose of about 10 μg of RNA is administered by (i) diluting the pharmaceutical RNA preparation about 1:1 and (ii) administering about 200 pl of the diluted pharmaceutical RNA preparation. In some embodiments, RNA in a pharmaceutical RNA preparation is present at a concentration of about 0.1 mg/ml, and is formulated in about 10 mM Tris buffer, and about 10% sucrose and a dose of RNA of about 10 μg is administered by (i) diluting the pharmaceutical RNA preparation about 1:5.75 and (ii) administering about 200 pl of diluted pharmaceutical RNA preparation.

[0016] The present disclosure generally embraces immunotherapeutic treatment of a subject comprising administration of RNA, e.g., vaccine RNA, encoding an amino acid sequence, e.g., a vaccine antigen, comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, i.e., an antigenic peptide or protein. Thus, vaccine antigen comprises an epitope of SARS-CoV-2 S protein for inducing an immune response against coronavirus S protein, in particular SARS-CoV-2 S protein, in the subject. RNA encoding vaccine antigen is administered to provide (following expression of the polynucleotide by appropriate target cells) antigen for induction, i.e., stimulation, priming and/or expansion, of an immune response, e.g., antibodies and/or immune effector cells, which is targeted to target antigen (coronavirus S protein, in particular SARS-CoV-2 S protein) or a procession product thereof. In one embodiment, the immune response which is to be induced according to the present disclosure is a B cell- mediated immune response, i.e., an antibody-mediated immune response. Additionally or alternatively, in one embodiment, the immune response which is to be induced according to the present disclosure is a T cell- mediated immune response. In one embodiment, the immune response is an anti-coronavirus, in particular anti- SARS-CoV-2 immune response.

[0017] In some embodiments, compositions (e.g., vaccines) described herein comprise as an active principle single-stranded RNA that may be translated into protein upon entering cells of a recipient. In addition to wildtype or codon-optimized sequences encoding an antigen sequence, RNA may contain one or more structural elements optimized for maximal efficacy with respect to stability and translational efficiency (e.g., 5' cap, 5' UTR, 3' UTR, poly(A)-tail, and combinations thereof). In one embodiment, RNA contains all of these elements. In one embodiment, a capl structure may be utilized as specific capping structure at the 5'-end of an RNA drug substance. In one embodiment, beta-S-ARCA(Dl) (m27,2'-OGppSpG) or m27,3'-OGppp(ml2'-O)ApG may be utilized as specific capping structure at the 5'-end of an RNA drug substance. As 5'-UTR sequence, the 5'-UTR sequence of the human alpha-globin mRNA, optionally with an optimized 'Kozak sequence' to increase translational efficiency (e.g., SEQ ID NO: 12) may be used. As 3’-UTR sequence, a combination of two sequence elements (FI element) derived from the "amino terminal enhancer of split" (AES) mRNA (called F) and the mitochondrial encoded 12S ribosomal RNA (called I) (e.g., SEQ ID NO: 13) placed between the coding sequence and the poly(A)-tail to assure higher maximum protein levels and prolonged persistence of the mRNA may be used. These features were identified by an ex vivo selection process for sequences that confer RNA stability and augment total protein expression (see WO 2017/060314, herein incorporated by reference). Alternatively, the 3’- UTR may be two re-iterated 3'-UTRs of the human beta-globin mRNA. Additionally or alternatively, in some embodiments, a poly(A)-tail may comprise a length of at least 100 adenosine residues (including, e.g., at least 110 adenosine residues, at least 120 adenosine residues, 130 adenosine residues, or longer). In some embodiments, a poly(A)-tai I may comprise a length of about 100 to about 150 adenosine residues. In some embodiments a poly(A)-tail may comprise an interrupted poly(A)-tail . For example, in some such embodiments, a poly(A)-tail measuring 110 nucleotides in length, consisting of a stretch of 30 adenosine residues, followed by a 10 nucleotide linker sequence (of random nucleotides) and another 70 adenosine residues (e.g., SEQ ID NO: 14) may be used. This poly(A)-tail sequence was designed to enhance RNA stability and translational efficiency. [0018] Furthermore, in some embodiments, a nucleotide sequence encoding a secretory signal peptide (sec) may be fused to antigen-encoding regions of an RNA, preferably in some embodiments in a way that the sec is translated as an N terminal tag. In one embodiment, sec corresponds to the secretory signal peptide of a SARS- CoV-2 S protein (e.g., of a Wuhan strain). In some embodiments, sequences coding for short linker peptides predominantly consisting of the amino acids glycine (G) and serine (S), as commonly used for fusion proteins, may be used as GS/Linkers between sec and an antigen.

[0019] In some embodiments, RNA described herein may be complexed with proteins and/or lipids, preferably lipids, to generate RNA-particles for administration. If a combination of different RNAs is used, RNAs may be complexed together or complexed separately with proteins and/or lipids to generate RNA-particles for administration.

[0020] In one aspect, the present disclosure relates to a composition or medical preparation comprising RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof.

[0021] In one embodiment, an immunogenic fragment of a coronavirus S protein (e.g., the SARS-CoV-2 S protein) comprises the SI subunit of the coronavirus S protein (e.g., SARS-CoV-2 S protein), or the receptor binding domain (RBD) of the SI subunit of the coronavirus S protein (e.g., SARS-CoV-2 S protein). In one embodiment, an immunogenic fragment of a coronavirus S protein (e.g., SARS-CoV-2 S protein) comprises an S2 subunit of the coronavirus S protein (e.g., SARS-CoV-2 S protein). In one embodiment, an immunogenic fragment of a coronavirus S protein (e.g., SARS-CoV-2 S protein) comprises a stem helix and/or fusion peptide of a coronavirus S protein (e.g., SARS-CoV-2 S protein).

[0022] In one embodiment, an amino acid sequence comprising a coronavirus (e.g., SARS-CoV-2) S protein, an immunogenic variant thereof, or an immunogenic fragment of the coronavirus (e.g., SARS-CoV-2) S protein or the immunogenic variant thereof is able to form a multimeric complex, in particular a trimeric complex. To this end, an amino acid sequence comprising a coronavirus (e.g., SARS-CoV-2) S protein, an immunogenic variant thereof, or an immunogenic fragment of the coronavirus (e.g., SARS-CoV-2) S protein or the immunogenic variant thereof may comprise a domain allowing the formation of a multimeric complex. In some embodiments a multimeric complex is a trimeric complex. In some embodiments, a multimeric complex comprises more than 3 polypeptides. In some embodiments, the compositions described herein can result in the delivery of a multimeric (e.g., trimeric) complex of the amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the coronavirus (e.g., SARS-CoV-2) S protein or the immunogenic variant thereof. In one embodiment, the domain allowing formation of a multimeric complex comprises a trimerization domain, for example, a trimerization domain as described herein, e.g., SARS-CoV-2 S protein trimerization domain. In one embodiment, trimerization is achieved by addition of a trimerization domain, e.g., a T4-fibritin- derived "foldon" trimerization domain (e.g., SEQ ID NO: 10), in particular if the amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof corresponds to a portion of a SARS-CoV-2 S protein that does not comprise the SARS-CoV-2 S protein trimerization domain.

[0023] In one embodiment, the amino acid sequence comprising a coronavirus (e.g., SARS-CoV-2) S protein, an immunogenic variant thereof, or an immunogenic fragment of the coronavirus (e.g., SARS-CoV-2) S protein or the immunogenic variant thereof is encoded by a coding sequence which is codon-optimized and/or the G/C content of which is increased compared to wild type coding sequence, wherein the codon-optimization and/or the increase in the G/C content preferably does not change the sequence of the encoded amino acid sequence.

Those skilled in the art will appreciate that codon optimization involves choosing between or among alternative codons encoding the same amino acid residue. Codon optimization typically includes consideration of codon(s) preferred by a particular host in which a sequence is to be expressed. In accordance with the present disclosure, in many embodiments, a preferred host is a human. In some embodiments, a preferred host may be a domestic animal. Alternatively or additionally, in some embodiments, selection between or among possible codons encoding the same amino acid may consider one or more other features such as, for example, overall G/C content (as noted above) and/or similarity to a particular reference. For example, in some embodiments of the present disclosure, a provided coding sequence that encodes a SARS-CoV-2 S protein or immunogenic variant thereof that differs in amino acid sequence from that encoded by a BNT162b2 construct described herein utilizes a codon, in at least one position of such difference, that preserves greater similarity to the BNT162b2 construct sequence relative to at least one alternative codon encoding the same amino acid at such position of difference. [0024] In one embodiment, an RNA is a modified RNA, in particular a stabilized mRNA. In one embodiment, an RNA comprises a modified nucleoside in place of at least one uridine. In one embodiment, an RNA comprises a modified nucleoside in place of each uridine. In one embodiment, the modified nucleoside is independently selected from pseudouridine (ip), Nl-methyl-pseudouridine (mlip), and 5-methyl-uridine (m5U).

[0025] In one embodiment, RNA comprises a modified nucleoside in place of uridine.

[0026] In one embodiment, the modified nucleoside is selected from pseudouridine (ip), Nl-methyl- pseudouridine (mlip), and 5-methyl-uridine (m5U).

[0027] In one embodiment, RNA comprises a 5' cap.

[0028] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a 5' UTR comprising the nucleotide sequence of SEQ ID NO: 12, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 12.

[0029] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a 3' UTR comprising the nucleotide sequence of SEQ ID NO: 13, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 13.

[0030] SEQ ID NO: 13:

CTGGTACTGCATGCACGCAATGCTAGCTGCCCCTTTCCCGTCCTGGGTACCCCGAGTCTCCCCCGACCTCGGGTCCCAGGTA TGCTCCCACCTCCACCTGCCCCACTCACCACCTCTGCTAGTTCCAGACACCTCCCAAGCACGCAGCAATGCAGCTCAAAACGC TTAGCCTAGCCACACCCCCACGGGAAACAGCAGTGATTAACCTTTAGCAATAAACGAAAGTTTAACTAAGCTATACTAACCCC AGGGTTGGTCAATTTCGTGCCAGCCACACC (SEQ ID NO: 13). [0031] In some embodiments, an RNA disclosed herein comprises a 3' UTR having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to a 3' UTR with the sequence of CUCGAGCUGGUACUGCAUGCACGCAAUGCUAGCUGCCCCUUUCCCGUCCUGGGUACCCCGAGUCUCCCCCGACCUCGGGU CCCAGGUAUGCUCCCACCUCCACCUGCCCCACUCACCACCUCUGCUAGUUCCAGACACCUCCCAAGCACGCAGCAAUGCAG CUCAAAACGCUUAGCCUAGCCACACCCCCACGGGAAACAGCAGUGAUUAACCUUUAGCAAUAAACGAAAGUUUAACUAAGC UAUACUAACCCCAGGGUUGGUCAAUUUCGUGCCAGCCACACC (SEQ ID NO: 601).

[0032] In some embodiments, an RNA disclosed herein comprises a 3' UTR with the sequence of CUCGAGCUGGUACUGCAUGCACGCAAUGCUAGCUGCCCCUUUCCCGUCCUGGGUACCCCGAGUCUCCCCCGACCUCGGGU CCCAGGUAUGCUCCCACCUCCACCUGCCCCACUCACCACCUCUGCUAGUUCCAGACACCUCCCAAGCACGCAGCAAUGCAG CUCAAAACGCUUAGCCUAGCCACACCCCCACGGGAAACAGCAGUGAUUAACCUUUAGCAAUAAACGAAAGUUUAACUAAGC UAUACUAACCCCAGGGUUGGUCAAUUUCGUGCCAGCCACACC (SEQ ID NO: 601).

[0033] In some embodiments, an RNA disclosed herein comprises a 3' UTR having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to a 3' UTR with the sequence of CUCGAGCUGGUACUGCAUGCACGCAAUGCUAGCUGCCCCUUUCCCGUCCUGGGUACCCCGAGUCUCCCCCGACCUCGGGU CCCAGGUAUGCUCCCACCUCCACCUGCCCCACUCACCACCUCUGCUAGUUCCAGACACCUCCCAAGCACGCAGCAAUGCAG CUCAAAACGCUUAGCCUAGCCACACCCCCACGGGAAACAGCAGUGAUUAACCUUUAGCAAUAAACGAAAGUUUAACUAAGC UAUACUAACCCCAGGGUUGGUCAAUUUCGUGCCAGCCACACCCUGGAGCUAGC (SEQ ID NO: 602).

[0034] In some embodiments, an RNA disclosed herein comprises a 3' UTR with the sequence of CUCGAGCUGGUACUGCAUGCACGCAAUGCUAGCUGCCCCUUUCCCGUCCUGGGUACCCCGAGUCUCCCCCGACCUCGGGU CCCAGGUAUGCUCCCACCUCCACCUGCCCCACUCACCACCUCUGCUAGUUCCAGACACCUCCCAAGCACGCAGCAAUGCAG CUCAAAACGCUUAGCCUAGCCACACCCCCACGGGAAACAGCAGUGAUUAACCUUUAGCAAUAAACGAAAGUUUAACUAAGC UAUACUAACCCCAGGGUUGGUCAAUUUCGUGCCAGCCACACCCUGGAGCUAGC (SEQ ID NO: 602)

[0035] In some embodiments, a 3'UTR is an FI element as described in W02017/060314, which is herein incorporated by reference in its entirety.

[0036] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a poly-A sequence.

[0037] In one embodiment, the poly-A sequence comprises at least 100 nucleotides.

[0038] In one embodiment, the poly-A sequence comprises or consists of the nucleotide sequence of SEQ ID NO: 14.

[0039] In one embodiment, RNA is formulated or is to be formulated as a liquid, a solid, or a combination thereof.

[0040] In one embodiment, RNA is formulated or is to be formulated for injection.

[0041] In one embodiment, RNA is formulated or is to be formulated for intramuscular administration.

[0042] In one embodiment, RNA is formulated or is to be formulated as particles.

[0043] In one embodiment, particles are lipid nanoparticles (LNP) or lipoplex (LPX) particles.

[0044] In one embodiment, LNPs comprise ((4-hydroxybutyl)azanediyl)bis(hexane-6,l-diyl)bis(2- hexyldecanoate), 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, l,2-Distearoyl-sn-glycero-3- phosphocholine, and cholesterol. [0045] In one embodiment, RNA lipoplex particles are obtainable by mixing RNA with liposomes. In one embodiment, RNA lipoplex particles are obtainable by mixing RNA with lipids.

[0046] In one embodiment, RNA is formulated or is to be formulated as colloid. In one embodiment, RNA is formulated or is to be formulated as particles, forming the dispersed phase of a colloid. In one embodiment, 50% or more, 75% or more, or 85% or more of RNA is present in the dispersed phase. In one embodiment, RNA is formulated or is to be formulated as particles comprising RNA and lipids. In one embodiment, particles are formed by exposing RNA, dissolved in an aqueous phase, with lipids, dissolved in an organic phase. In one embodiment, the organic phase comprises ethanol. In one embodiment, particles are formed by exposing RNA, dissolved in an aqueous phase, with lipids, dispersed in an aqueous phase. In one embodiment, the lipids dispersed in an aqueous phase form liposomes.

[0047] In one embodiment, RNA is mRNA or saRNA.

[0048] In one embodiment, a composition or medical preparation is a pharmaceutical composition.

[0049] In one embodiment, a composition or medical preparation is a vaccine.

[0050] In one embodiment, a pharmaceutical composition further comprises one or more pharmaceutically acceptable carriers, diluents and/or excipients.

[0051] In one embodiment, a composition or medical preparation is a kit.

[0052] In one embodiment, RNA and optionally the particle forming components are in separate vials.

[0053] In one embodiment, a kit further comprises instructions for use of a composition or medical preparation for inducing an immune response against coronavirus in a subject.

[0054] In one aspect, the present disclosure relates to a composition or medical preparation described herein for pharmaceutical use.

[0055] In one embodiment, a pharmaceutical use comprises inducing an immune response against coronavirus in a subject.

[0056] In one embodiment, a pharmaceutical use comprises a therapeutic or prophylactic treatment of a coronavirus infection.

[0057] In one embodiment, a composition or medical preparation described herein is for administration to a human.

[0058] In one embodiment, the coronavirus is a betacoronavirus.

[0059] In one embodiment, the coronavirus is a sarbecovirus.

[0060] In one embodiment, the coronavirus is SARS-CoV-2.

[0061] In one aspect, the present disclosure relates to a method of inducing an immune response against coronavirus in a subject comprising administering to the subject a composition comprising RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof.

[0062] In one embodiment, an immunogenic fragment of the SARS-CoV-2 S protein comprises the SI subunit of the SARS-CoV-2 S protein, or the receptor binding domain (RBD) of the SI subunit of the SARS-CoV-2 S protein.

[0063] In one embodiment, an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof is able to form a multimeric complex, in particular a trimeric complex. To this end, an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS- CoV-2 S protein or the immunogenic variant thereof may comprise a domain allowing the formation of a multimeric complex, in particular a trimeric complex of the amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof. In one embodiment, the domain allowing the formation of a multimeric complex comprises a trimerization domain, for example, a trimerization domain as described herein.

[0064] In one embodiment, an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof is encoded by a coding sequence which is codon-optimized and/or the G/C content of which is increased compared to wild type coding sequence, wherein the codon-optimization and/or the increase in the G/C content preferably does not change the sequence of the encoded amino acid sequence.

[0065] In one embodiment, an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a secretory signal peptide.

[0066] In one embodiment, a secretory signal peptide is fused, preferably N-terminally, to a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof.

[0067] In one embodiment,

(i) the RNA encoding the secretory signal peptide comprises the nucleotide sequence of nucleotides 1 to 48 of SEQ ID NO: 2, 8 or 9, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 1 to 48 of SEQ ID NO: 2, 8 or 9, or a fragment of the nucleotide sequence of nucleotides 1 to 48 of SEQ ID NO: 2, 8 or 9, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 1 to 48 of SEQ ID NO: 2, 8 or 9; and/or

(ii) the secretory signal peptide comprises the amino acid sequence of amino acids 1 to 16 of SEQ ID NO: 1, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 16 of SEQ ID NO: 1, or a functional fragment of the amino acid sequence of amino acids 1 to 16 of SEQ ID NO: 1, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 16 of SEQ ID NO: 1.

[0068] In one embodiment, a composition described herein comprises an RNA molecule comprising a nucleotide sequence encoding a SARS-CoV-2 S protein comprising one or more mutations characteristic of an XBB.1.5, XBB.1.16, BA.4/5, XBB, XBB.l, XBB.2.3, XBB.2.3.2, BQ.1.1, KP.2, JN.l, or XEC Omicron variant or sublineages (i.e., descendants) thereof.

[0069] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.1.5 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, V83A, G142D, A145, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486P, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0070] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of a BA.4/5 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, A69/70, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1. [0071] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of a BA.2.75 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, G142D, K147E, W152R, F157L, I210V, V213G, G257S, G339H, N354D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, G446S, N460K, S477N, T478K, E484A, Q498R, N501Y, Y505H D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0072] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of a BA.2.75.2 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, G142D, K147E, W152R, F157L, I210V, V213G, G257S, G339H, R346T, N354D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, G446S, N460K, S477N, T478K, E484A, F486S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K, and D1199N, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0073] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of a BA.4.6/BF.7 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, A69/70, G142D, V213G, G339D, R346T, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N658S, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0074] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of an XBB variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, V213E, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486S, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0075] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.l variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486S, F490S, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0076] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.l.16 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, V83A, G142D, A145, H146Q, E180V, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478R, E484A, F486P, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0077] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.2.3 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, V213E, D253G, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486P, F490S, Q498R, N501Y, P521S, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0078] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.2.3.2 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, G184V, V213E, D253G, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486P, F490S, Q498R, N501Y, P521S, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0079] In one embodiment, a composition described herein comprises a nucleotide sequence that encodes a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing comprising one or more mutations characteristic of a BQ.1.1 variant, wherein the one or more mutations are selected from the group consisting of T19I, A24-26, A27S, A69/70, G142D, V213G, G339D, R346T, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, K444T, L452R, N460K, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K, wherein the mutations are indicated relative to SEQ ID NO: 1.

[0080] In one embodiment, a SARS-CoV-2 S protein, a variant thereof, or a truncated fragment of either of the foregoing encoded by an RNA described herein comprises one or more substitutions that stable a prefusionconfirmation. In one embodiment, the one or more substitutions that stabilize a prefusion confirmation are proline substitutions at positions corresponding to K986 and V987 of SEQ ID NO: 1.

[0081] In one embodiment, an RNA molecule comprises at least at least one modified uridine in place of a uridine. In one embodiment, an RNA molecule comprises a modified uridine in place of each uridine.

[0082] In one embodiment, an RNA molecule comprises a 5' cap. In some embodiments, the 5' cap comprises (e.g., consists of) m27,3'-OGppp(ml2'-O)ApG.

[0083] In one embodiment, an RNA molecule comprises a 5' untranslated region (UTR). In one embodiment, the 5' UTR comprises a human alpha-globin 5'-UTR. In one embodiment, the human alpha-globin 5' untranslated region (UTR) comprises SEQ ID NO: 12.

[0084] In one embodiment, an RNA molecule comprises a 3' UTR. In one embodiment, the 3' UTR comprises a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA. In one embodiment, the 3' UTR comprises SEQ ID NO: 13. In one embodiment, the 3' UTR comprises SEQ ID NO: 601. In one embodiment, the 3' UTR comprises SEQ ID NO: 602. [0085] In one embodiment, an RNA molecule comprises a poly-A sequence of at least 100 A nucleotides. In one embodiment, the poly-A sequence comprises 30 adenine nucleotides followed by 70 adenine nucleotides, wherein the 30 adenine nucleotides and 70 adenine nucleotides are separated by a linker sequence. In some embodiments, the poly-A sequence comprises SEQ ID NO: 14. [0086] In one embodiment, an RNA comprises a nucleotide sequence encoding a SARS-CoV-2 S protein, wherein the sequence is codon-optimized (e.g., codon-optimized for expression in human cells) and/or which has a G/C content that is increased compared to a wild type coding sequence.

[0087] In some embodiments, an RNA molecule is encapsulated in a lipid nanoparticle (LNP). In some embodiments, the LNP comprises molar ratios of 20-60% ionizable cationic lipid, 5-25% neutral lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid.

[0088] In some embodiments, a composition described herein is formulated as a liquid, a solid, or a combination thereof.

[0089] In some embodiments, a composition described herein is formulated for injection. In some embodiments, a composition described herein is formulated for intramuscular administration.

[0090] In some embodiments, an RNA described herein is mRNA.

[0091] In some embodiments, an RNA described herein is saRNA.

[0092] In some embodiments, a composition described herein is a pharmaceutical composition. In some embodiments, a pharmaceutical composition further comprises one or more pharmaceutically acceptable carriers, diluents and/or excipients. In some embodiments, a composition described herein is a vaccine.

[0093] In some embodiments, the present disclosure provides a method of eliciting an immune response in a subject, where the method comprising administering a composition described herein. In some embodiments, the immune response is elicited against an Omicron variant of SARS-CoV-2. In some embodiments, the immune response is elicited against a Wuhan strain, an Omicron variant, a Beta variant, an Alpha variant, and a Delta variant of SARS-CoV-2.

[0094] In some embodiments, a composition described herein is administered to a subject that has not been previously infected with and/or has not been previously administered a SARS-CoV-2 vaccine.

[0095] In some embodiments, a composition described herein is adminsitered to a subject that has previously been infected with SARS-CoV-2 and/or has been previously administered a SARS-CoV-2 vaccine. [0096] In some embodiments, a composition described herein is adminsitered to a subject who has previously received a vaccine that delivers a SARS-CoV-2 S protein of a Wuhan strain (e.g., a full length protein or an antigenic fragment thereof).

[0097] In some embodiments, a composition described herein is adminsitered to subject who has previously been administered RNA encoding a SARS-CoV-2 S protein of a Wuhan strain (e.g., a full length protein or an antigenic fragment thereof).

[0098] In some embodiments, a composition described herein is adminsitered to subject who has previously been administered two or more doses of RNA encoding a SARS-CoV-2 S protein of a Wuhan strain. [0099] In some embodiments, a composition described herein is adminsitered to subject who has previously been administered:

(i) two or more doses of RNA encoding a SARS-CoV-2 S protein of a Wuhan strain (e.g., BNT162b2); and

(ii) one or more doses of a bivalent vaccine comprising:

(a) a first RNA comprising a nucleotide sequence encoding a SARS-CoV-2 S protein of a Wuhan strain; and

(b) a second RNA comprising a nucleoside sequence encoding a SARS-CoV-2 S protein of an Omicron BA.4/5 variant.

[00100] In some embodiments, a composition described herein is administered to a subject who has previously been administered one or more doses of a bivalent vaccine comprising (1) a first RNA that comprises a nucleotide sequence of that is at least 90% identical to that set forth in SEQ ID NO: 20 (e.g., at least 95% identical, at least 96% identical, at least 97% identical, at least 99% identical, or 100% identical), and

(2) a second RNA that comprises a nucleotide sequence that is at least 90% identical to that set forth in SEQ ID NO: 72 (e.g., at least 95% identical, at least 96% identical, at least 97% identical, at least 99% identical, or 100% identical).

[OO1O1] In some embodiments, a composition described herein comprises about 3 μg to about 30 μg of RNA (e.g., about 3 pg, about 10 pg, or about 30 μg of RNA).

[00102] In some embodiments, a composition described herein comprises about 3 μg of RNA, and is administered to a subject who is about 6 months to less than about 5 years old.

[00103] In some embodiments, a composition described herein comprises about 10 μg of RNA, and is administered to a subject who is about 5 years old to less than about 12 years old.

[00104] In some embodiments, a composition described herein comprises about 30 μg of RNA, and is administered to a subject who is about 12 years or older.

[00105] In some embodiments, a composition described herein is co-administered with one or more vaccines against a non-SARS-CoV-2 disease (e.g., a non-SARS-CoV-2 respiratory disease). In some embodiments, the one or more vaccines against a non-SARS-CoV-2 disease comprises an influenza vaccine, an RSV vaccine, or a combination thereof.

[00106] In some embodiments, the present disclosure provides a kit comprising a composition described herein. In some embodiments the kit further comprises instructions for use of the composition to induce an immune response against coronavirus in a subject.

[00107] In some embodiments, a composition described herein is for pharmaceutical use. In some embodiments, the pharmaceutical use comprises inducing an immune response against coronavirus (e.g., a betacoronavirus, a sarbecovirus, or a SARS-CoV-2 virus) in a subject. In some embodiments, an immune response is induced in a human. In some embodiments, the pharmaceutical use comprises a therapeutic or prophylactic treatment of a coronavirus (e.g., a betacoronavirus, a sarbecovirus, or a SARS-CoV-2 virus) infection. [00108] In some embodiments, a composition described herein is for administration to a human.

[00109] In some embodiments, a composition described herein is for pharmaceutical use. In some embodiments, the pharmaceutical use comprises inducing an immune response against coronavirus in a subject. In some embodiments, the pharmaceutical use comprises a therapeutic or prophylactic treatment of a coronavirus (e.g., a betacoronavirus, a sarbecovirus, or a SARS-CoV-2 virus) infection.

[00110] In some embodiments, described herein is the use of a composition described herein for the manufacture of a medicament for inducing an immune response against coronavirus in a subject. In some embodiments, the medicament is for therapeutic or prophylactic treatment of a coronavirus (e.g., a betacoronavirus, a sarbecovirus, or a SARS-CoV-2 virus) infection.

[00111] In some embodiments, a composition comprises an RNA molecule comprising:

(i) Nl-methyl-pseudouridine in place of each uridine; and

(ii) a 5' cap that comprises m27,3'-OGppp(ml2'-O)ApG; wherein the RNA molecule is encapsulated in a lipid nanoparticle (LNP); and wherein the LNP comprises molar ratios of 20-60% ionizable cationic lipid, 5-25% neutral lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid. [00112] In some embodiments, a composition described herein comprises about 10 mM Tris buffer and about 10% sucrose.

[00113] In some embodiment, a composition comprises at least one unit dose of LNP-encapsulated RNA molecules, optionally wherein the unit dose comprises the RNA molecule in an amount of about 30 pg, or wherein the unit dose comprises the RNA molecule in an amount of about 10 pg, or wherein the unit dose comprises the RNA molecule in an amount of about 3 pg.

[00114] In some embodiments, a composition described herein is formulated as a multi-dose formulation in a vial.

[00115] In some embodiments, a composition described herein is for use in a method of inducing an immune response against coronavirus in a subject, said method comprising administering to a subject the composition. In some embodiments: the subject is 12 years or older, and the composition comprises 30 μg of the RNA molecule, or the subject is 5 years to less than 12 years old, and the composition comprises 10 pg of the RNA molecule, or the subject is 6 months to less than 5 years old, and the composition comprises 3 pg of the RNA molecule. [00116] In some embodiments, a composition described herein is administered in a volume of about 200 pL to 300 μL.

[00117] In some embodiments, a composition described herein is adminsitered to a subject previously administered one or more doses of a SARS-CoV-2 vaccine, preferably wherein the subject was previously administered a complete dosing regimen of a SARS-CoV-2 vaccine.

[00118] In some embodiments, a composition described herein is adminsitered to a subject previously administered a first dose and a second dose of BNT162b2, wherein the first dose and the second dose were administered about 21 days apart, and/or wherein the subject was previously administered as a booster dose a bivalent vaccine that delivers (i) a SARS-CoV-2 S protein of an Omicron BA.4/5 variant and (ii) a SARS-CoV-2 S protein of a Wuhan strain.

[00119] In some embodiments, a composition described herein is co-administered with one or more vaccines against a non-SARS-CoV-2 disease, preferably wherein the one or more vaccines comprises an RSV vaccine, an influenza vaccine, or a combination thereof.

[00120] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a 5' UTR comprising the nucleotide sequence of SEQ ID NO: 12, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 12.

[00121] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a 3' UTR comprising the nucleotide sequence of SEQ ID NO: 13, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 13.

[00122] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a 3' UTR comprising the nucleotide sequence of SEQ ID NO: 601, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 601.

[00123] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a 3' UTR comprising the nucleotide sequence of SEQ ID NO: 602, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 602.

[00124] In one embodiment, RNA encoding an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a poly-A sequence.

[00125] In one embodiment, a poly-A sequence comprises at least 100 nucleotides.

[00126] In one embodiment, a poly-A sequence comprises or consists of the nucleotide sequence of SEQ ID

NO: 14.

[00127] In one embodiment, RNA is formulated as a liquid, a solid, or a combination thereof.

[00128] In one embodiment, RNA is formulated as particles.

[00129] In one embodiment, the particles are lipid nanoparticles (LNP) or lipoplex (LPX) particles. [00130] In one embodiment, LNPs comprise ((4-hydroxybutyl)azanediyl)bis(hexane-6,l-diyl)bis(2- hexyldecanoate), 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, l,2-Distearoyl-sn-glycero-3- phosphocholine, and cholesterol.

[00131] In one embodiment, RNA lipoplex particles are obtainable by mixing RNA with liposomes. In one embodiment, RNA lipoplex particles are obtainable by mixing RNA with lipids.

[00132] In one embodiment, RNA is formulated as colloid. In one embodiment, RNA is formulated as particles, forming the dispersed phase of a colloid. In one embodiment, 50% or more, 75% or more, or 85% or more of RNA are present in the dispersed phase. In one embodiment, RNA is formulated as particles comprising RNA and lipids. In one embodiment, particles are formed by exposing RNA, dissolved in an aqueous phase, with lipids, dissolved in an organic phase. In one embodiment, the organic phase comprises ethanol. In one embodiment, particles are formed by exposing RNA, dissolved in an aqueous phase, with lipids, dispersed in an aqueous phase. In one embodiment, the lipids dispersed in an aqueous phase form liposomes.

[00133] In one embodiment, a method disclosed herein is a method for vaccination against coronavirus.

[00134] In one embodiment, a method disclosed herein is a method for therapeutic or prophylactic treatment of a coronavirus infection.

[00135] In one embodiment, a subject is a human.

[00136] In one embodiment, the coronavirus is a betacoronavirus.

[00137] In one embodiment, the coronavirus is a sarbecovirus.

[00138] In one embodiment, the coronavirus is SARS-CoV-2.

[00139] In one embodiment of methods described herein, a composition described herein is administered to a subject.

[00140] In one aspect, the present disclosure relates to a composition or medical preparation described herein for use in a method described herein.

[00141] Among other things, the present disclosure teaches that a composition comprising a lipid nanoparticle encapsulated RNA encoding at least a portion (e.g., that is or comprises an epitope) of a SARS-CoV- 2-encoded polypeptide (e.g., of a SARS-CoV-2-encoded S protein) can achieve detectable antibody titer against an epitope in serum within 7 days after administration to a population of adult human subjects according to a regimen that includes administration of at least one dose of the composition. Moreover, the present disclosure teaches persistence of such antibody titer. In some embodiments, such antibody titer is increased when a modified mRNA is used, as compared with titer achieved with a corresponding unmodified mRNA.

[00142] In some embodiments, a provided regimen includes at least one dose. In some embodiments, a provided regimen includes a first dose and at least one subsequent dose. In some embodiments, the first dose is the same amount as at least one subsequent dose. In some embodiments, the first dose is the same amount as all subsequent doses. In some embodiments, the first dose is a different amount as at least one subsequent dose. In some embodiments, the first dose is a different amount than all subsequent doses. In some embodiments, a provided regimen comprises two doses. In some embodiments, a provided regimen consists of two doses.

[00143] In particular embodiments, an immunogenic composition is formulated as a single-dose in a container, e.g., a vial. In some embodiments, an immunogenic composition is formulated as a multi-dose formulation in a vial. In some embodiments, the multi-dose formulation includes at least 2 doses per vial. In some embodiments, the multi-dose formulation includes a total of 2-20 doses per vial, such as, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 doses per vial. In some embodiments, each dose in the vial is equal in volume. In some embodiments, a first dose is a different volume than a subsequent dose.

[00144] A "stable" multi-dose formulation exhibits no unacceptable levels of microbial growth, and substantially no or no breakdown or degradation of the active biological molecule component(s). As used herein, a "stable" immunogenic composition includes a formulation that remains capable of eliciting a desired immunologic response when administered to a subject.

[00145] In some embodiments, a multi-dose formulation remains stable for a specified time with multiple or repeated inoculations/insertions into the multi-dose container. For example, in some embodiments a multi-dose formulation may be stable for at least three days with up to ten usages, when contained within a multi-dose container. In some embodiments, multi-dose formulations remain stable with 2-20 inoculations/insertions.

[00146] In some embodiments, administration of a composition comprising a lipid nanoparticle encapsulated RNA (e.g., in some embodiments mRNA) encoding at least a portion (e.g., that is or comprises an epitope) of a SARS-CoV-2-encoded polypeptide (e.g., of a SARS-CoV-2-encoded S protein), e.g., according to a regimen as described herein, may result in lymphopenia in some subjects (e.g., in all subjects, in most subjects, in about 50% or fewer, in about 40% or fewer, in about 40% or fewer, in about 25% or fewer, in about 20% or fewer, in about 15% or fewer, in about 10% or fewer, in about 5% or fewer, etc). Among other things, the present disclosure teaches that such lymphopenia can resolve over time. For example, in some embodiments, lymphopenia resolves within about 14, about 10, about 9, about 8, about 7 days or less. In some embodiments, lymphopenia is Grade 3, Grade 2, or less.

[00147] Thus, among other things, the present disclosure provides compositions comprising a lipid nanoparticle encapsulated RNA (e.g., in some embodiments mRNA) encoding at least a portion (e.g., that is or comprises an epitope) of a SARS-CoV-2-encoded polypeptide (e.g., of a SARS-CoV-2-encoded S protein) that are characterized, when administered to a relevant population of adults, to display certain characteristics (e.g., achieve certain effects) as described herein. In some embodiments, provided compositions may have been prepared, stored, transported, characterized, and/or used under conditions where temperature does not exceed a particular threshold. Alternatively or additionally, in some embodiments, provided compositions may have been protected from light (e.g., from certain wavelengths) during some or all of their preparation, storage, transport, characterization, and/or use. In some embodiments, one or more features of provided compositions (e.g., RNA stability, as may be assessed, for example, by one or more of size, presence of particular moiety or modification, etc; lipid nanoparticle stability or aggregation, pH, etc) may be or have been assessed at one or more points during preparation, storage, transport, and/or use prior to administration.

[00148] Among other things, the present disclosure documents that certain provided compositions in which nucleotides within an RNA (e.g., in some embodiments mRNA) are not modified (e.g., are naturally-occurring A, U, C, G), and/or provided methods relating to such compositions, are characterized (e.g., when administered to a relevant population, which may in some embodiments be or comprise an adult population), by an intrinsic adjuvant effect. In some embodiments, such a composition and/or method can induce an antibody and/or a T cell response. In some embodiments, such a composition and/or method can induce a higher T cell response, as compared to conventional vaccines (e.g., non-RNA vaccines such as protein vaccines).

[00149] Alternatively or additionally, the present disclosure documents that provided compositions (e.g., compositions comprising a lipid nanoparticle encapsulated RNA encoding at least a portion (e.g., that is or comprises an epitope) of a SARS-CoV-2-encoded polypeptide (e.g., of a SARS-CoV-2-encoded S protein)) in which nucleotides within an RNA are modified, and/or provided methods relating to such compositions, are characterized (e.g., when administered to a relevant population, which may in some embodiments be or comprise an adult population), by absence of an intrinsic adjuvant effect, or by a reduced intrinsic adjuvant effect as compared with an otherwise comparable composition (or method) with unmodified results. Alternatively or additionally, in some embodiments, such compositions (or methods) are characterized in that they (e.g., when administered to a relevant population, which may in some embodiments be or comprise an adult population) induce an antibody response and/or a CD4+ T cell response. Still further alternatively or additionally, in some embodiments, such compositions (or methods) are characterized in that they (e.g., when administered to a relevant population, which may in some embodiments be or comprise an adult population) induce a higher CD4+ T cell response than that observed with an alternative vaccine format (e.g., a peptide vaccine). In some embodiments involving modified nucleotides, such modified nucleotides may be present, for example, in a 3' UTR sequence, an antigen-encoding sequence, and/or a 5'UTR sequence. In some embodiments, modified nucleotides are or include one or more modified uracil residues and/or one or more modified cytosine residues. [00150] Among other things, the present disclosure documents that provided (e.g., compositions comprising a lipid nanoparticle encapsulated RNA encoding at least a portion (e.g., that is or comprises an epitope) of a SARS-CoV-2-encoded polypeptide (e.g., of a SARS-CoV-2-encoded S protein)) and/or methods are characterized by (e.g., when administered to a relevant population, which may in some embodiments be or comprise an adult population) sustained expression of an encoded polypeptide (e.g., of a SARS-CoV-2-encoded protein [such as an S protein] or portion thereof, which portion, in some embodiments, may be or comprise an epitope thereof). For example, in some embodiments, such compositions and/or methods are characterized in that, when administered to a human, they achieve detectable polypeptide expression in a biological sample (e.g., serum) from such human and, in some embodiments, such expression persists for a period of time that is at least at least 36 hours or longer, including, e.g., at least 48 hours, at least 60 hours, at least 72 hours, at least 96 hours, at least 120 hours, at least 148 hours, or longer.

[00151] Those skilled in the art, reading the present disclosure, will appreciate that it describes various RNA constructs (e.g., in some embodiments mRNA constructs) encoding at least a portion (e.g., that is or comprises an epitope) of a SARS-CoV-2-encoded polypeptide (e.g., of a SARS-CoV-2-encoded S protein)). Such person of ordinary skill, reading the present disclosure, will particularly appreciate that it describes various RNA constructs (e.g., in some embodiments mRNA constructs) encoding at least a portion of a SARS-CoV-2 S protein, for example at least an RBD portion of a SARS-CoV-2 S protein. Still further, such a person of ordinary skill, reading the present disclosure, will appreciate that it describes particular characteristics and/or advantages of RNA constructs (e.g., in some embodiments mRNA constructs) encoding at least a portion (e.g., that is or comprises an epitope) of a SARS-CoV-2-encoded polypeptide (e.g., of a SARS-CoV-2-encoded S protein). In some embodiments, an RNA construct (e.g., in some embodiments, an mRNA construct) may encode at least one domain of a SARS-CoV-2 encoded polypeptide (e.g., one or more domains of a SARS-CoV-2 encoded polypeptide as described in WO 2021/159040, including, e.g., an N-terminal domain (NTD) of a SARS-CoV-2 Spike protein, a receptor binding domain (RBD) of a SARS- CoV-2 Spike protein, Heptapeptide repeat sequence 1 (HR1) of a SARS-CoV-2 Spike protein, Heptapeptide repeat sequence 2 (HR1) of a SARS-CoV-2 Spike protein, and/or combinations thereof). Among other things, the present disclosure particularly documents surprising and useful characteristics and/or advantages of certain RNA constructs (e.g., in some embodiments mRNA constructs) encoding a SARS-CoV-2 RBD portion and, in some embodiments, not encoding a full length SARS-CoV-2 S protein. Without wishing to be bound by any particular theory, the present disclosure suggests that provided RNA constructs (e.g., in some embodiments mRNA constructs) that encode less than a full-length SARS-CoV-2 S protein, and particularly those that encode at least an RBD portion of such SARS-CoV-2 S protein may be particularly useful and/or effective for use as or in an immunogenic composition (e.g., a vaccine), and/or for achieving immunological effects as described herein (e.g., generation of SARS-CoV-2 neutralizing antibodies, and/or T cell responses (e.g., CD4+ and/or CD8+ T cell responses)).

[00152] In some embodiments, the present disclosure provides an RNA (e.g., mRNA) comprising an open reading frame encoding a polypeptide that comprises a receptor-binding portion of a SARS-CoV-2 S protein, which RNA is suitable for intracellular expression of the polypeptide. In some embodiments, such an encoded polypeptide does not comprise the complete S protein. In some embodiments, an encoded polypeptide comprises the receptor binding domain (RBD), for example, as shown in SEQ ID NO: 5. In some embodiments, the encoded polypeptide comprises the peptide according to SEQ ID NO: 29 or 31. In some embodiments, such an RNA (e.g., mRNA) may be complexed by a (poly)cationic polymer, polyplex(es), protein(s) or peptide(s). In some embodiments, such an RNA may be formulated in a lipid nanoparticle (e.g., ones described herein). In some embodiments, such an RNA (e.g., mRNA) may be particularly useful and/or effective for use as or in an immunogenic composition (e.g., a vaccine), and/or for achieving immunological effects as described herein (e.g., generation of SARS-CoV-2 neutralizing antibodies, and/or T cell responses (e.g., CD4+ and/or CD8+ T cell responses)). In some embodiments, such an RNA (e.g., mRNA) may be useful for vaccinating humans (including, e.g., humans known to have been exposed and/or infected by SARS-CoV-2, and/or humans not known to have been exposed to SARS-CoV-2).

[00153] Those skilled in the art, reading the present disclosure, will further appreciate that it describes various mRNA constructs comprising a nucleic acid sequence that encodes a full-length SARS-CoV-2 Spike protein (e.g., including embodiments in which such encoded SARS-CoV-2 Spike protein may comprise at least one or more amino acid substitutions, e.g., proline substitutions as described herein, and/or embodiments in which the mRNA sequence is codon-optimized e.g., for mammalian, e.g., human, subjects). In some embodiments, such a full-length SARS-CoV-2 Spike protein may have an amino acid sequence that is or comprises that set forth in SEQ ID NO: 7. Still further, such a person of ordinary skill, reading the present disclosure, will appreciate, among other things, that it describes particular characteristics and/or advantages of certain mRNA constructs comprising a nucleic acid sequence that encodes a full-length SARS-CoV-2 Spike protein. Without wishing to be bound by any particular theory, the present disclosure suggests that provided mRNA constructs that encode a full-length SARS- CoV-2 S protein may be particularly useful and/or effective for use as or in an immunogenic composition (e.g., a vaccine) in particular subject population (e.g., particular age populations). For example, in some embodiments, such an mRNA composition may be particularly useful in younger (e.g., less than 25 years old, 20 years old, 18 years old, 15 years, 10 years old, or lower) subjects; alternatively or additionally, in some embodiments, such an mRNA composition may be particularly useful in elderly subjects (e.g., over 55 years old, 60 years old, 65 years old, 70 years old, 75 years old, 80 years old, 85 years old, or higher). In particular embodiments, an immunogenic composition comprising such an mRNA construct provided herein exhibits a minimal to modest increase (e.g., no more than 30% increase, no more than 20% increase, or no more than 10% increase, or lower) in dose level and/or dose number-dependent systemic reactogenicity (e.g., fever, fatigue, headache, chills, diarrhea, muscle pain, and/or joint pain, etc.) and/or local tolerability (e.g., pain, redness, and/or swelling, etc.), at least in some subjects (e.g., in some subject age groups); in some embodiments, such reactogenicity and/or local tolerability is observed particularly, in in younger age group (e.g., less than 25 years old, 20 years old, 18 years old or lower) subjects, and/or in older (e.g., elderly) age group (e.g., 65-85 years old). In some embodiments, provided mRNA constructs that encode a full-length SARS-CoV-2 S protein may be particularly useful and/or effective for use as or in an immunogenic composition (e.g., a vaccine) for inducing SARS-CoV-2 neutralizing antibody response level in a population of subjects that are at high risk for severe diseases associated with SARS-CoV-2 infection (e.g., an elderly population, for example, 65-85 year-old group). In some embodiments, a person of ordinary skill, reading the present disclosure, will appreciate, among other things, that provided mRNA constructs that encode a full-length SARS-CoV-2 S protein, which exhibit a favorable reactogenicity profile (e.g., as described herein) in younger and elderly age populations, may be particularly useful and/or effective for use as or in an immunogenic composition (e.g., a vaccine) for achieving immunological effects as described herein (e.g., generation of SARS-CoV-2 neutralizing antibodies, and/or T cell responses (e.g., CD4+ and/or CD8+ T cell responses)). In some embodiments, the present disclosure also suggests that provided mRNA constructs that encode a full-length SARS-CoV-2 S protein may be particularly effective to protect against SARS-CoV-2 infection, as characterized by earlier clearance of SARS-CoV-2 viral RNA in non-human mammalian subjects (e.g., rhesus macaques) that were immunized with immunogenic compositions comprising such mRNA constructs and subsequently challenged by SARS-CoV-2 strain. In some embodiments, such earlier clearance of SARS-CoV-2 viral RNA may be observed in the nose of non-human mammalian subjects (e.g., rhesus macaques) that were immunized with immunogenic compositions comprising such mRNA constructs and subsequently challenged by SARS-CoV-2 strain.

[00154] In some embodiments, the present disclosure provides an RNA (e.g., mRNA) comprising an open reading frame encoding a full-length SARS-CoV-2 S protein (e.g., a full-length SARS-CoV-2 S protein with one or more amino acid substitutions), which RNA is suitable for intracellular expression of the polypeptide. In some embodiments, the encoded polypeptide comprises the amino acid sequence of SEQ ID NO:7. In some embodiments, such an RNA (e.g., mRNA) may be complexed by a (poly)cationic polymer, polyplex(es), protein(s) or peptide(s). In some embodiments, such an RNA may be formulated in a lipid nanoparticle (e.g., ones described herein).

[00155] In some embodiments, an immunogenic composition provided herein may comprise a plurality of (e.g., at least two or more, including, e.g., at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, etc.) immunoreactive epitopes of a SARS-CoV-2 polypeptide or variants thereof. In some such embodiments, such a plurality of immunoreactive epitopes may be encoded by a plurality of RNAs (e.g., mRNAs). In some such embodiments, such a plurality of immunoreactive epitopes may be encoded by a single RNA (e.g., mRNA). In some embodiments, nucleic acid sequences encoding a plurality of immunoreactive epitopes may be separated from each other in a single RNA (e.g., mRNA) by a linker (e.g., a peptide linker in some embodiments). Without wishing to be bound by any particular theory, in some embodiments, provided polyepitope immunogenic compositions (including, e.g., those that encode a full-length SARS-CoV-2 spike protein) may be particularly useful, when considering the genetic diversity of SARS-CoV-2 variants, to provide protection against numerous viral variants and/or may offer a greater opportunity for development of a diverse and/or otherwise robust (e.g., persistent, e.g., detectable about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 or more days after administration of one or more doses) neutralizing antibody and/or T cell response, and in particular a particularly robust THl-type T cell (e.g., CD4+ and/or CD8+ T cell) response. [00156] In some embodiments, the present disclosure documents that provided compositions and/or methods are characterized by (e.g., when administered to a relevant population, which may in some embodiments be or comprise an adult population) in that they achieve one or more particular therapeutic outcomes (e.g., effective immune responses as described herein and/or detectable expression of encoded SARS- CoV-2 S protein or an immunogenic fragment thereof) with a single administration; in some such embodiments, an outcome may be assessed, for example, as compared to that observed in absence of RNA vaccines (e.g., mRNA vaccines) described herein. In some embodiments, a particular outcome may be achieved at a lower dose than required for one or more alternative strategies.

[00157] In some embodiments, the present disclosure provides an immunogenic composition comprising an isolated messenger ribonucleic acid (mRNA) polynucleotide, wherein the isolated mRNA polynucleotide comprises an open reading frame encoding a polypeptide that comprises a receptor-binding portion of a SARs-CoV-2 S protein, and wherein the isolated mRNA polynucleotide is formulated in at least one lipid nanoparticle. For example, in some embodiments, such a lipid nanoparticle may comprise a molar ratio of 20-60% ionizable cationic lipid, 5-25% non-cationic lipid (e.g., neutral lipid), 25-55% sterol or steroid, and 0.5-15% polymer- conjugated lipid (e.g., PEG-modified lipid). In some embodiments, a sterol or steroid included in a lipid nanoparticle may be or comprise cholesterol. In some embodiments, a neutral lipid may be or comprise 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC). In some embodiments, a polymer-conjugated lipid may be or comprise PEG2000 DMG. In some embodiments, such an immunogenic composition may comprise a total lipid content of about 1 mg to 10 mg, or 3 mg to 8 mg, or 4 mg to 6 mg. In some embodiments, such an immunogenic composition may comprise a total lipid content of about 5 mg/mL -15 mg/mL or 7.5 mg/mL- 12.5 mg/mL or 9-11 mg/mL. In some embodiments, such an isolated mRNA polynucleotide is provided in an effective amount to induce an immune response in a subject administered at least one dose of the immunogenic composition. In some embodiments, a polypeptide encoded by a provided isolated mRNA polynucleotide does not comprise the complete S protein. In some embodiments, such an isolated mRNA polynucleotide provided in an immunogenic composition is not self-replicating RNA.

[00158] In some embodiments, an immune response may comprise generation of a binding antibody titer against SARS-CoV-2 protein (including, e.g., a stabilized prefusion spike trimer in some embodiments) or a fragment thereof. In some embodiments, an immune response may comprise generation of a binding antibody titer against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. In some embodiments, a provided immunogenic composition has been established to achieve a detectable binding antibody titer after administration of a first dose, with seroconversion in at least 70% (including, e.g., at least 80%, at least 90%, at least 95% and up to 100%) of a population of subjects receiving such a provided immunogenic composition, for example, by about 2 weeks.

[00159] In some embodiments, an immune response may comprise generation of a neutralizing antibody titer against SARS-CoV-2 protein (including, e.g., a stabilized prefusion spike trimer in some embodiments) or a fragment thereof. In some embodiments, an immune response may comprise generation of a neutralizing antibody titer against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. In some embodiments, a provided immunogenic composition has been established to achieve a neutralizing antibody titer in an appropriate system (e.g., in a human infected with SARS-CoV-2 and/or a population thereof, and/or in a model system therefor). For example, in some embodiments, such neutralizing antibody titer may have been demonstrated in one or more of a population of humans, a non-human primate model (e.g., rhesus macaques), and/or a mouse model.

[00160] In some embodiments, a neutralizing antibody titer is a titer that is (e.g., that has been established to be) sufficient to reduce viral infection of B cells relative to that observed for an appropriate control (e.g., an unvaccinated control subject, or a subject vaccinated with a live attenuated viral vaccine, an inactivated viral vaccine, or a protein subunit viral vaccine, or a combination thereof). In some such embodiments, such reduction is of at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more.

[00161] In some embodiments, a neutralizing antibody titer is a titer that is (e.g., that has been established to be) sufficient to reduce the rate of asymptomatic viral infection relative to that observed for an appropriate control (e.g., an unvaccinated control subject, or a subject vaccinated with a live attenuated viral vaccine, an inactivated viral vaccine, or a protein subunit viral vaccine, or a combination thereof). In some such embodiments, such reduction is of at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more. In some embodiments, such reduction can be characterized by assessment of SARS- CoV-2 N protein serology. Significant protection against asymptomatic infection was also confirmed by real life observations (see also: Dagan N. et al., N Engl J Med. 2021, doi: 10.1056/NEJMoa2101765. Epub ahead of print. PMID: 33626250)

[00162] In some embodiments, a neutralizing antibody titer is a titer that is (e.g., that has been established to be) sufficient to reduce or block fusion of virus with epithelial cells and/or B cells of a vaccinated subject relative to that observed for an appropriate control (e.g., an unvaccinated control subject, or a subject vaccinated with a live attenuated viral vaccine, an inactivated viral vaccine, or a protein subunit viral vaccine, or a combination thereof). In some such embodiments, such reduction is of at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more.

[00163] In some embodiments, induction of a neutralizing antibody titer may be characterized by an elevation in the number of B cells, which in some embodiments may include plasma cells, class-switched IgGl- and IgG2-positive B cells, and/or germinal center B cells. In some embodiments, a provided immunogenic composition has been established to achieve such an elevation in the number of B cells in an appropriate system (e.g., in a human infected with SARS-CoV-2 and/or a population thereof, and/or in a model system therefor). For example, in some embodiments, such an elevation in the number of B cells may have been demonstrated in one or more of a population of humans, a non-human primate model (e.g., rhesus macaques), and/or a mouse model. In some embodiments, such an elevation in the number of B cells may have been demonstrated in draining lymph nodes and/or spleen of a mouse model after (e.g., at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, after) immunization of such a mouse model with a provided immunogenic composition. [00164] In some embodiments, induction of a neutralizing antibody titer may be characterized by a reduction in the number of circulating B cells in blood. In some embodiments, a provided immunogenic composition has been established to achieve such a reduction in the number of circulating B cells in blood of an appropriate system (e.g., in a human infected with SARS-CoV-2 and/or a population thereof, and/or in a model system therefor). For example, in some embodiments, such a reduction in the number of circulating B cells in blood may have been demonstrated in one or more of a population of humans, a non-human primate model (e.g., rhesus macaques), and/or a mouse model. In some embodiments, such a reduction in the number of circulating B cells in blood may have been demonstrated in a mouse model after (e.g., at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, after) immunization of such a mouse model with a provided immunogenic composition. Without wishing to be bound by theory, a reduction in circulating B cells in blood may be due to B cell homing to lymphoid compartments.

[00165] In some embodiments, an immune response induced by a provided immunogenic composition may comprise an elevation in the number of T cells. In some embodiments, such an elevation in the number of T cells may include an elevation in the number of T follicular helper (TFH) cells, which in some embodiments may comprise one or more subsets with ICOS upregulation. One of skilled in the art will understand that proliferation of TFH in germinal centres is integral for generation of an adaptive B-cell response, and also that in humans, TFH occurring in the circulation after vaccination is typically correlated with a high frequency of antigen-specific antibodies. In some embodiments, a provided immunogenic composition has been established to achieve such an elevation in the number of T cells (e.g., TFH cells) in an appropriate system (e.g., in a human infected with SARS- CoV-2 and/or a population thereof, and/or in a model system therefor). For example, in some embodiments, such an elevation in the number of T cells (e.g., TFH cells) may have been demonstrated in one or more of a population of humans, a non-human primate model (e.g., rhesus macaques), and/or a mouse model. In some embodiments, such an elevation in the number of T cells (e.g., e.g., TFH cells) may have been demonstrated in draining lymph nodes, spleen, and/or blood of a mouse model after (e.g., at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, after) immunization of such a mouse model with a provided immunogenic composition.

[00166] In some embodiments, a protective response against SARS-CoV-2 induced by a provided immunogenic composition has been established in an appropriate model system for SARS-CoV-2. For example, in some embodiments, such a protective response may have been demonstrated in an animal model, e.g., a non- human primate model (e.g., rhesus macaques) and/or a mouse model. In some embodiments, a non-human primate (e.g., rhesus macaque) or a population thereof that has/have received at least one immunization with a provided immunogenic composition is/are challenged with SARS-CoV-2, e.g., through intranasal and/or intratracheal route. In some embodiments, such a challenge may be performed several weeks (e.g., 5-10 weeks) after at least one immunization (including, e.g., at least two immunizations) with a provided immunogenic composition. In some embodiments, such a challenge may be performed when a detectable level of a SARS-CoV- 2 neutralizing titer (e.g., antibody response to SARS-CoV-2 spike protein and/or a fragment thereof, including, e.g., but not limited to a stabilized prefusion spike trimer, S-2P, and/or antibody response to receptor-binding portion of SARS-CoV-2) is achieved in non-human primate(s) (e.g., rhesus macaque(s)) that has received at least one immunization (including, e.g., at least two immunizations) with a provided immunogenic composition. In some embodiments, a protective response is characterized by absence of or reduction in detectable viral RNA in bronchoalveolar lavage (BAL) and/or nasal swabs of challenged non-human primate(s) (e.g., rhesus macaque(s)). In some embodiments, immunogenic compositions described herein may have been characterized in that a larger percent of challenged animals, for example, non-human primates in a population (e.g., rhesus macaques), that have received at least one immunization (including, e.g., at least two immunizations) with a provided immunogenic composition display absence of detectable RNA in their BAL and/or nasal swab, as compared to a population of non-immunized animals, for example, non-human primates (e.g., rhesus macaques). In some embodiments, immunogenic compositions described herein may have been characterized in that challenged animals, for example, non-human in a population (e.g., rhesus macaques), that have received at least one immunization (including, e.g., at least two immunizations) with a provided immunogenic composition may show clearance of viral RNA in nasal swab no later than 10 days, including, e.g., no later than 8 days, no later than 6 days, no later than 4 days, etc., as compared to a population of non-immunized animals, for example, non-human primates (e.g., rhesus macaques).

[00167] In some embodiments, immunogenic compositions described herein when administered to subjects in need thereof do not substantially increase the risk of vaccine-associated enhanced respiratory disease. In some embodiments, such vaccine-associated enhanced respiratory disease may be associated with antibody-dependent enhancement of replication and/or with vaccine antigens that induced antibodies with poor neutralizing activity and Th2-biased responses. In some embodiments, immunogenic compositions described herein when administered to subjects in need thereof do not substantially increase the risk of antibody-dependent enhancement of replication.

[00168] In some embodiments, a single dose of an RNA composition (e.g., mRNA formulated in lipid nanoparticles) can induce a therapeutic antibody response in less than 10 days of vaccination. In some embodiments, such a therapeutic antibody response may be characterized in that when such an RNA vaccine can induce production of about 10-100 ug/mL IgG measured at 10 days after vaccination at a dose of 0.1 to 10 ug or 0.2- 5 ug in an animal model. In some embodiments, such a therapeutic antibody response may be characterized in that such an RNA vaccine induces about 100-1000 ug/mL IgG measured at 20 days of vaccination at a dose of 0.1 to 10 ug or 0.2- 5 ug in an animal model. In some embodiments, a single dose may induce a pseudovirusneutralization titer, as measured in an animal model, of 10-200 pVN50 titer 15 days after vaccination. In some embodiments, a single dose may induce a pseudovirus-neutralization titer, as measured in an animal model, of 50-500 pVN50 titer 15 days after vaccination.

[00169] In some embodiments, a single dose of an RNA composition (e.g., mRNA composition) can expand antigen-specific CD8 and/or CD4 T cell response by at least at 50% or more (including, e.g., at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or more), as compared to that observed in absence of such an RNA construct encoding a SARS-COV2 immunogenic protein or fragment thereof (e.g., spike protein and/or receptor binding domain). In some embodiments, a single dose of an RNA composition can expand antigenspecific CD8 and/or CD4 T cell response by at least at 1.5-fold or more (including, e.g., at least 2-fold, at least 3- fold, at least 5-fold, at least 10-fold, at least 50-fold, at least 100-fold, at least 500-fold, at least 1000-fold, or more), as compared to that observed in absence of such an RNA construct encoding a SARS-COV2 immunogenic protein or fragment thereof (e.g., spike protein and/or receptor binding domain).

[00170] In some embodiments, a regimen (e.g., a single dose of an mRNA composition) can expand T cells that exhibit a Thl phenotype (e.g., as characterized by expression of IFN-gamma, IL-2, IL-4, and/or IL-5) by at least at 50% or more (including, e.g., at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or more), as compared to that observed in absence of such an mRNA construct encoding a SARS-COV2 immunogenic protein or fragment thereof (e.g., spike protein and/or receptor binding domain). In some embodiments, a regimen (e.g., a single dose of an mRNA composition) can expand T cells that exhibit a Thl phenotype (e.g., as characterized by expression of IFN-gamma, IL-2, IL-4, and/or IL-5), for example by at least at 1.5-fold or more (including, e.g., at least 2-fold, at least 3-fold, at least 5-fold, at least 10-fold, at least 50-fold, at least 100-fold, at least 500-fold, at least 1000-fold, or more), as compared to that observed in absence of such an mRNA construct encoding a SARS-COV2 immunogenic protein or fragment thereof (e.g., spike protein and/or receptor binding domain). In some embodiments, a T-cell phenotype may be or comprise a Thl-dominant cytokine profile (e.g., as characterized by INF-gamma positive and/or IL-2 positive), and/or no by or biologically insignificant IL-4 secretion.

[00171] In some embodiments, a regimen as described herein (e.g., one or more doses of an mRNA composition) induces and/or achieves production of RBD-specific CD4+ T cells. Among other things, the present disclosure documents that mRNA compositions encoding an RBD-containing portion of a SARS-CoV-2 spike protein (e.g., and not encoding a full-length SARS-CoV-2 spike protein) may be particularly useful and/or effective in such induction and/or production of RBD-specific CD4+ T cells. In some embodiments, RBD-specific CD4+ T- cells induced by an mRNA composition described herein (e.g., by an mRNA composition that encodings an RBD- containing-portion of a SARS-CoV-2 spike protein and, in some embodiments not encoding a full-length SARS- CoV-2 spike protein) demonstrate a Thl-dominant cytokine profile (e.g., as characterized by INF-gamma positive and/or IL-2 positive), and/or by no or biologically insignificant IL-4 secretion.

[00172] In some embodiments, characterization of CD4+ and/or CD8+ T cell responses (e.g., described herein) in subjects receiving RNA compositions (e.g., as described herein) may be performed using ex vivo assays using PBMCs collected from the subjects.

[00173] In some embodiments, immunogenicity of RNA (e.g., mRNA) compositions described herein may be assessed by one of or more of the following serological immunongenicity assays: detection of IgG, IgM, and/or IgA to SARS-CoV-2 S protein present in blood samples of a subject receiving a provided RNA composition, and/or neutralization assays using SARS-CoV-2 pseudovirus and/or a wild-type SARS-CoV-2 virus.

[00174] In some embodiments, an RNA composition (e.g., as described herein) provide a relatively low adverse effect (e.g., Grade 1-Grade 2 pain, redness and/or swelling) within 7 days after vaccinations at a dose of 10 ug - 100 ug or 1 ug-50 ug. In some embodiments, RNA compositions (e.g., as described herein) provide a relatively low observation of systemic events (e.g., Grade 1-Grade 2 fever, fatigue, headache, chills, vomiting, diarrhea, muscle pain, joint pain, medication, and combinations thereof ) within 7 days after vaccinations at a dose of 10 ug - 100 ug.

[00175] In some embodiments, RNA (e.g., mRNA) compositions are characterized in that when administered to subjects at 10-100 ug dose or 1 ug-50 ug, IgG directed to a SARS-CoV2 immunogenic protein or fragment thereof (e.g., spike protein and/or receptor binding domain) may be produced at a level of 100-100,000 U/mL or 500-50,000 U/mL 21 days after vaccination.

[00176] In some embodiments, an RNA (e.g., mRNA) encodes a natively-folded trimeric receptor binding protein of SARS-CoV-2. In some embodiments, an RNA (e.g., mRNA) encodes a variant of such receptor binding protein such that the encoded variant binds to ACE2 at a Kd of 10 pM or lower, including, e.g., at a Kd of 9 pM, 8 pM, 7 pM, 6 pM, 5 pM, 4 pM, or lower. In some embodiments, an RNA (e.g., mRNA) encodes a variant of such receptor binding protein such that the encoded variant binds to ACE2 at a Kd of 5 pM. In some embodiments, an RNA (e.g., mRNA) encodes a trimeric receptor binding portion of SARS-CoV-2 that comprises an ACE2 receptor binding site. In some embodiments, an RNA (e.g., mRNA) comprises a coding sequence for a receptor-binding portion of SARS-CoV-2 and a trimerization domain (e.g., a natural trimerization domain (foldon) of T4 fibritin) such that the coding sequence directs expression of a trimeric protein that has an ACE2 receptor binding site and binds ACE2. In some embodiments, an RNA (e.g., mRNA) encodes a trimeric receptor binding portion of SARS- CoV-2 or a variant thereof such that its Kd is smaller than that for a monomeric receptor-binding domain (RBD) of SARS-CoV-2. For example, in some embodiments, an RNA (e.g., mRNA) encodes a trimeric receptor binding portion of SARS-CoV-2 or a variant thereof such that its Kd is at least 10-fold (including, e.g., at least 50-fold, at least 100-fold, at least 500-fold, at least 1000-fold, etc.) smaller than that for a RBD of SARS-CoV-2.

[00177] In some embodiments, a trimer receptor binding portion of SARS-CoV-2 encoded by an RNA (e.g., as described herein) may be determined to have a size of about 3-4 angstroms when it is complexed with ACE2 and B0AT1 neutral amino acid transporter in a closed conformation, as characterized by electron cryomicroscopy (cryoEM). In some embodiments, geometric mean SARS-CoV-2 neutralizing titer that characterizes and/or is achieved by an RNA composition or method as described herein can reach at least 1.5-fold, including, at least 2- fold, at least 2.5-fold, at least 3-fold, or higher, that of a COVID-19 convalescent human panel (e.g., a panel of sera from COVID-19 convalescing humans obtained 20-40 days after the onset of symptoms and at least 14 days after the start of asymptomatic convalescence.

[00178] In some embodiments, RNA compositions as provided herein may be characterized in that subjects who have been treated with such compositions (e.g., with at least one dose, at least two doses, etc) may show reduced and/or more transient presence of viral RNA in relevant site(s) (e.g., nose and/or lungs, etc, and/or any other tissue susceptible to infection) as compared with an appropriate control (e.g., an established expected level for a comparable subject or population not having been so treated and having been exposed to virus under reasonably comparable exposure conditions)

[00179] In some embodiments, the RBD antigen expressed by an mRNA construct (e.g., as described herein) can be modified by addition of a T4-fibritin-derived "foldon" trimerization domain, for example, to increase its immunogenicity.

[00180] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that certain local reactions (e.g., pain, redness, and/or swelling, etc.) and/or systemic events (e.g., fever, fatigue, headache, etc.) may appear and/or peak at Day 2 after vaccination. In some embodiments, RNA (e.g., mRNA) compositions described herein are characterized in that certain local reactions (e.g., pain, redness, and/or swelling, etc.) and/or systemic events (e.g., fever, fatigue, headache, etc.) may resolve by Day 7 after vaccination.

[00181] In some embodiments, RNA compositions (e.g., mRNA) and/or methods described herein are characterized in that no Grade 1 or greater change in routine clinical laboratory values or laboratory abnormalities are observed in subjects receiving RNA compositions (e.g., as described herein). Examples of such clinical laboratory assays may include lymphocyte count, hematological changes, etc.

[00182] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that by 21 days after a first dose (e.g., 10-100 ug inclusive or 1 ug-50 ug inclusive), geometric mean concentrations (GMCs) of IgG directed to a SARS-CoV-2 S polypeptide or an immunogenic fragment thereof (e.g., RBD) may reach 200-3000 units/mL or 500-3000 units/mL or 500-2000 units/mL, compared to 602 units/mL for a panel of COVID-19 convalescent human sera. In some embodiments, RNA (e.g., mRNA) compositions described herein are characterized in that by 7 days after a second dose (e.g., 10-30 ug inclusive; or 1 ug-50 ug inclusive), geometric mean concentrations (GMCs) of IgG directed to a SARS-CoV-2 spike polypeptide or an immunogenic fragment thereof (e.g., RBD) may increase by at least 8-fold or higher, including, e.g., at least 9-fold, at least 10-fold, at least 15-fold, at least 20-fold, at least 25-fold, at least 30-fold, at least 35- fold, at least 40-fold, or higher. In some embodiments, RNA (e.g., mRNA) compositions described herein are characterized in that by 7 days after a second dose (e.g., 10-30 ug inclusive; or 1 ug-50 ug inclusive), geometric mean concentrations (GMCs) of IgG directed to a SARS-CoV-2 S polypeptide or an immunogenic fragment thereof (e.g., RBD) may increase to 1500 units/mL to 40,000 units/mL or 4000 units/mL to 40,000 units/mL. In some embodiments, antibody concentrations described herein can persist to at least 20 days or longer, including, e.g., at least 25 days, at least 30 days, at least 35 days, at least 40 days, at least 45 days, at least 50 days, after a first dose, or at least 10 days or longer, including, e.g., at least 15 days, at least 20 days, at least 25 days, or longer, after a second dose. In some embodiments, antibody concentrations can persist to 35 days after a first dose, or at least 14 days after a second dose.

[00183] In some embodiments, RNA (e.g., mRNA) compositions described herein are characterized in that when measured at 7 days after a second dose (e.g., 1-50 ug inclusive), GMC of IgG directed to a SARS-CoV-2 S polypeptide or an immunogenic fragment thereof (e.g., RBD) is at least 30% higher (including, e.g., at least 40% higher, at least 50% higher, at least 60%, higher, at least 70% higher, at least 80% higher, at least 90% higher, at least 95 % higher, as compared to antibody concentrations observed in a panel of COVID-19 convalescent human serum. In many embodiments, geometric mean concentration (GMC) of IgG described herein is GMCs of RBD-binding IgG.

[00184] In some embodiments, RNA (e.g., mRNA) compositions described herein are characterized in that when measured at 7 days after a second dose (e.g., 10-50 ug inclusive), GMC of IgG directed to a SARS-CoV-2 S polypeptide or an immunogenic fragment thereof (e.g., RBD) is at least 1.1-fold higher (including, e.g., at least 1.5-fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold higher, at least 7-fold higher, at least 8-fold higher, at least 9-fold higher, at least 10-fold higher, at least 15-fold higher, at least 20-fold higher, at least 25-fold higher, at least 30-fold higher), as compared to antibody concentrations observed in a panel of COVID-19 convalescent human serum, In many embodiments, geometric mean concentration (GMC) of IgG described herein is GMCs of RBD-binding IgG.

[00185] In some embodiments, RNA (e.g., mRNA) compositions described herein are characterized in that when measured at 21 days after a second dose, GMC of IgG directed to a SARS-CoV-2 S polypeptide or an immunogenic fragment thereof (e.g., RBD) is at least 5-fold higher (including, e.g., at least 6-fold higher, at least 7-fold higher, at least 8-fold higher, at least 9-fold higher, at least 10-fold higher, at least 15-fold higher, at least 20-fold higher, at least 25-fold higher, at least 30-fold higher), as compared to antibody concentrations observed in a panel of COVID-19 convalescent human serum, In many embodiments, geometric mean concentration (GMC) of IgG described herein is GMCs of RBD-binding IgG.

[00186] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that an increase (e.g., at least 30%, at least 40%, at least 50%, or more) in SARS-CoV-2 neutralizing geometric mean titers (GMTs) is observed 21 days after a first dose. In some embodiments, RNA (e.g., mRNA) compositions described herein are characterized in that a substantially greater serum neutralizing GMTs are achieved 7 days after subjects receive a second dose (e.g., 10 pg-30 μg inclusive), reaching 150-300, compared to 94 for a COVID-19 convalescent serum panel.

[00187] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that 7 days after administration of the second dose, the protective efficacy is at least 60%, e.g., at least 70%, at least 80%, at least 90, or at least 95%. In one embodiment, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that 7 days after administration of the second dose, the protective efficacy is at least 70%. In one embodiment, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that 7 days after administration of the second dose, the protective efficacy is at least 80%. In one embodiment, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that 7 days after administration of the second dose, the protective efficacy is at least 90%. In one embodiment, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that 7 days after administration of the second dose, the protective efficacy is at least 95%.

[00188] In some embodiments, an RNA composition provided herein is characterized in that it induces an immune response against SARS-CoV-2 after at least 7 days after a dose (e.g., after a second dose). In some embodiments, an RNA composition provided herein is characterized in that it induces an immune response against SARS-CoV-2 in less than 14 days after a dose (e.g., after a second dose). In some embodiments, an RNA composition provided herein is characterized in that it induces an immune response against SARS-CoV-2 after at least 7 days after a vaccination regimen. In some embodiments, a vaccination regimen comprises a first dose and a second dose. In some embodiments, a first dose and a second dose are administered by at least 21 days apart. In some such embodiments, an immune response against SARS-CoV-2 is induced at least after 28 days after a first dose.

[00189] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that geometric mean concentration (GMCs) of antibodies directed to a SARS-CoV-2 spike polypeptide or an immunogenic fragment thereof (e.g., RBD), as measured in serum from subjects receiving RNA (e.g., mRNA) compositions of the present disclosure (e.g., at a dose of 10-30 ug inclusive), is substantially higher than in a convalescent serum panel (e.g., as described herein). In some embodiments where a subject may receive a second dose (e.g., 21 days after 1 first dose), geometric mean concentration (GMCs) of antibodies directed to a SARS-CoV-2 spike polypeptide or an immunogenic fragment thereof (e.g., RBD), as measured in serum from the subject, may be 8.0-fold to 50-fold higher than a convalescent serum panel GMC. In some embodiments where a subject may receive a second dose (e.g., 21 days after 1 first dose), geometric mean concentration (GMCs) of antibodies directed to a SARS-CoV-2 spike polypeptide or an immunogenic fragment thereof (e.g., RBD), as measured in serum from the subject, may be at least 8.0-fold or higher, including, e.g., at least 10-fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 60-fold or higher, as compared to a convalescent serum panel GMC.

[00190] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that the SARS-CoV-2 neutralizing geometric mean titer, as measured at 28 days after a first dose or 7 days after a second dose, may be at least 1.5-fold or higher (including, e.g., at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold or higher), as compared to a neutralizing GMT of a convalescent serum panel. [00191] In some embodiments, a regimen administered to a subject may be or comprise a single dose. In some embodiments, a regimen administered to a subject may comprise a plurality of doses (e.g., at least two doses, at least three doses, or more). In some embodiments, a regimen administered to a subject may comprise a first dose and a second dose, which are given at least 2 weeks apart, at least 3 weeks apart, at least 4 weeks apart, or more. In some embodiments, such doses may be at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, or more apart. In some embodiments, doses may be administered days apart, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 or more days apart. In some embodiments, doses may be administered about 1 to about 3 weeks apart, or about 1 to about 4 weeks apart, or about 1 to about 5 weeks apart, or about 1 to about 6 weeks apart, or about 1 to more than 6 weeks apart. In some embodiments, doses may be separated by a period of about 7 to about 60 days, such as for example about 14 to about 48 days, etc. In some embodiments, a minimum number of days between doses may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or more. In some embodiments, a maximum number of days between doses may be about 60, 59, 58, 57, 56, 55, 54, 53, 52, 51, 50, 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, TJ, 26, 25, 24, 23, 22, 21, or fewer. In some embodiments, doses may be about 21 to about 28 days apart. In some embodiments, doses may be about 19 to about 42 days apart. In some embodiments, doses may be about 7 to about 28 days apart. In some embodiments, doses may be about 14 to about 24 days. In some embodiments, doses may be about 21 to about 42 days.

[00192] In some embodiments, particularly for compositions established to achieve elevated antibody and/or T-cell titres for a period of time longer than about 3 weeks - e.g., in some embodiments, a provided composition is established to achieve elevated antibody and/or T-cell titres (e.g., specific for a relevant portion of a SARS-CoV- 2 spike protein) for a period of time longer than about 3 weeks; in some such embodiments, a dosing regimen may involve only a single dose, or may involve two or more doses, which may, in some embodiments, be separated from one another by a period of time that is longer than about 21 days or three weeks. For example, in some such embodiments, such period of time may be about 4 weeks, 5 weeks, 6 weeks 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 wees, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks or more, or about 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10, months, 11 months, 12 months or more, or in some embodiments about a year or more.

[00193] In some embodiments, a first dose and a second dose (and/or other subsequent dose) may be administered by intramuscular injection. In some embodiments, a first dose and a second dose may be administered in the deltoid muscle. In some embodiments, a first dose and a second dose may be administered in the same arm. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered (e.g., by intramuscular injection) as a series of two doses (e.g., 0.3 mL each) 21 days part. In some embodiments, each dose is about 30 ug. In some embodiments, each dose may be higher than 30 ug, e.g., about 40 ug, about 50 ug, about 60 ug. In some embodiments, each dose may be lower than 30 ug, e.g., about 20 ug, about 10 ug, about 5 ug, etc. In some embodiments, each dose is about 3 ug or lower, e.g., about 1 ug. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 16 or older (including, e.g., 16-85 years). In some such embodiments, an RNA composition (e.g., mRNA) described herein is administered to subjects of age 18-55. In some such embodiments, an RNA composition (e.g., mRNA) described herein is administered to subjects of age 56-85. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered (e.g., by intramuscular injection) as a single dose.

[00194] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that RBD-specific IgG (e.g., polyclonal response) induced by such RNA compositions and/or methods exhibit a higher binding affinity to RBD, as compared to a reference human monoclonal antibody with SARS-CoV-2 RBD-binding affinity (e.g., CR3022 as described in J. ter Meulen et al., PLOS Med. 3, e237 (2006).) [00195] In particular embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that sera of vaccinated subjects display neutralizing activity against SARs-CoV-2 spike variant "B.l.1.28".

[00196] In particular embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that sera of vaccinated subjects display neutralizing activity against SARs-CoV-2 spike variant "B.l.1.248". [00197] In particular embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that sera of vaccinated subjects display neutralizing activity against SARs-CoV-2 spike variant "501.V2".

[00198] In particular embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that sera of vaccinated subjects display neutralizing activity against SARs-CoV-2 spike variant "B.l.1.248".

[00199] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein are characterized in that sera of vaccinated subjects display neutralizing activity against SARs-CoV-2 spike variant of the Omicron (B.l.1.529) variant. Omicron (B.l.1.529) variant is a variant of SARS-CoV-2 which was detected in South Africa. Multiple Omicron variants or sublineages have arisen, including e.g., the BA.l, BA.2, BA.2.12.1, BA.3, BA.4, BA.5, BA.2.75, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, and XBB.2.3.2 sublineages. As used herein, unless otherwise specified, "Omicron variant" refers to the first disclosed Omicron variant (BA.l) or any variant thereof that has since arisen (e.g., Omicron variants described herein).

[00200] SARs-CoV-2 spike proteins encoded by RNA described herein may or may not include a D614G mutation as compared to SEQ ID NO: 1.

[00201] In some embodiments, SARS-CoV-2 spike proteins encoded by RNA described herein comprise a mutation in a furin cleavage site (e.g., in some embodiments residues 682-685 of SEQ ID NO: 1). In some embodiments, SARS-CoV-2 spike proteins encoded by RNA described herein comprise a mutation in the furin cleavage site that prevents cleavage by a furin protease (e.g., a human furin protease). In some embodiments, a SARS-CoV-2 protein described herein comprises a furin mutation disclosed in WO2021163365 or WO2021243122 (e.g., a GSAS mutation), the contents of both of which are incorporated by reference herein in their entirety. [00202] In some embodiments, RNA (e.g., mRNA) compositions and/or methods described herein can provide protection against SARS-CoV-2 and/or decrease severity of SARS-CoV-2 infection in at least 50% of subjects receiving such RNA compositions and/or methods.

[00203] In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include subjects of age 18-55. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include subjects of age 56-85. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include older subjects (e.g., over age 60, 65, 70, 75, 80, 85, etc, for example subjects of age 65-85). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include subjects of age 18-85. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include subjects of age 18 or younger. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include subjects of age 12 or younger. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include subjects of age 10 or younger. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include adolescent populations (e.g., individuals approximately 12 to approximately 17 years of age). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include pediatric populations (e.g., as described herein). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include infants (e.g., less than 1 year old). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein do not include infants (e.g., less than 1 year) whose mothers have received such RNA (e.g., mRNA) compositions described herein during pregnancy. Without wishing to be bound by any particular theory, a rat study has suggested that a SARS-CoV-2 neutralizing antibody response induced in female rats given such RNA compositions during pregnancy can pass onto fetuses. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein include infants (e.g., less than 1 year) whose mothers did not receive such RNA compositions described herein during pregnancy. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include pregnant women; in some embodiments, infants whose mothers were vaccinated during pregnancy (e.g., who received at least one dose, or alternatively only who received both doses), are not vaccinated during the first weeks, months, or even years (e.g., 1, 2, 3, 4, 5, 6, 7, 8 weeks or more, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 months or more, or 1, 2, 3, 4, 5 years or more) post-birth. Alternatively or additionally, in some embodiments, infants whose mothers were vaccinated during pregnancy (e.g., who received at least one dose, or alternatively only who received both doses), receive reduced vaccination (e.g., lower doses and/or smaller numbers of administrations - e.g., boosters - and/or lower total exposure over a given period of time) after birth, for example during the first weeks, months, or even years (e.g., 1, 2, 3, 4, 5, 6, 7, 8 weeks or more, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 months or more, or 1, 2, 3, 4, 5 years or more) post-birth or may need reduced vaccination (e.g., lower doses and/or smaller numbers of administrations - e.g., boosters - over a given period of time), In some embodiments, compositions as provided herein are administered to populations that do not include pregnant women.

[00204] In some particular embodiments, compositions as provided herein are administered to pregnant women according to a regimen that includes a first dose administered after about 24 weeks of gestation (e.g., after about 22, 23, 24, 25, 26, 27, 28 or more weeks of gestation); in some embodiments, compositions as provided herein are administered to pregnant women according to a regimen that includes a first dose administered before about 34 weeks of gestation (e.g., before about 30, 31, 32, 33, 34, 35, 36, 37, 38 weeks of gestation). In some embodiments, compositions as provided herein are administered to pregnant women according to a regimen that includes a first dose administered after about 24 weeks (e.g., after about 27 weeks of gestation, e.g., between about 24 weeks and 34 weeks, or between about 27 weeks and 34 weeks) of gestation and a second dose administered about 21 days later; in some embodiments both doses are administered prior to delivery. Without wishing to be bound by any particular theory, it is proposed that such a regimen (e.g., involving administration of a first dose after about 24 weeks, or 27 weeks of gestation and optionally before about 34 weeks of gestation), and optionally a second dose within about 21 days, ideally before delivery, may have certain advantages in terms of safety (e.g., reduced risk of premature delivery or of fetal morbidity or mortality) and/or efficacy (e.g., carryover vaccination imparted to the infant) relative to alternative dosing regimens (e.g., dosing at any time during pregnancy, refraining from dosing during pregnancy, and/or dosing later in pregnancy for example so that only one dose is administered during gestation. In some embodiments, infants born of mothers vaccinated during pregnancy, e.g., according to a particular regimen as described herein, may not need further vaccination, or may need reduced vaccination (e.g., lower doses and/or smaller numbers of administrations - e.g., boosters and/or lower overall exposure over a given period of time), for a period of time (e.g., as noted herein) after birth.

[00205] In some embodiments, compositions as provided herein are administered to populations in which women are advised against becoming pregnant for a period of time after receipt of the vaccine (e.g., after receipt of a first dose of the vaccine, after receipt of a final dose of the vaccine, etc.); in some such embodiments, the period of time may be at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks or more, or may be at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or more. [00206] In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include one or more populations with one or more particularly high risk conditions or history, e.g., as noted herein. For example, in some embodiments, populations to be treated with RNA compositions described herein may include subjects whose profession and/or environmental exposure may dramatically increase their risk of getting SARS-CoV-2 infection (including, e.g., but not limited to mass transportation, prisoners, grocery store workers, residents in long-term care facilities, butchers or other meat processing workers, healthcare workers, and/or first responders, e.g., emergency responders). In particular embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include healthcare workers and/or first responders, e.g., emergency responders. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include those with a history of smoking or vaping (e.g., within 6 months, 12 months or more, including a history of chronic smoking or vaping). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include certain ethnic groups that have been determined to be more susceptible to SARS-CoV-2 infection.

[00207] In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include certain populations with a blood type that may have been determined to more susceptible to SARS-CoV-2 infection. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include immunocompromised subjects (e.g., those with HIV/AIDS; cancer patients (e.g., receiving antitumor treatment); patients who are taking certain immunosuppressive drugs (e.g., transplant patients, cancer patients, etc.); autoimmune diseases or other physiological conditions expected to warrant immunosuppressive therapy (e.g., within 3 months, within 6 months, or more); and those with inherited diseases that affect the immune system (e.g., congenital agammaglobulinemia, congenital IgA deficiency)). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include those with an infectious disease. For example, in some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include those infected with human immunodeficiency virus (HIV) and/or a hepatitis virus (e.g., HBV, HCV). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include those with underlying medical conditions. Examples of such underlying medical conditions may include, but are not limited to hypertension, cardiovascular disease, diabetes, chronic respiratory disease, e.g., chronic pulmonary disease, asthma, etc., cancer, and other chronic diseases such as, e.g., lupus, rheumatoid arthritis, chronic liver diseases, chronic kidney diseases (e.g., Stage 3 or worse such as in some embodiments as characterized by a glomerular filtration rate (GFR) of less than 60 mL/min/1.73m2). In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include overweight or obese subjects, e.g., specifically including those with a body mass index (BMI) above about 30 kg/m2. In some embodiments, populations to be treated with RNA (e.g., mRNA) compositions described herein may include subjects who have prior diagnosis of COVID-19 or evidence of current or prior SARS-CoV-2 infection, e.g., based on serology or nasal swab. In some embodiments, populations to be treated include white and/or non-Hispanic/non-Latino.

[00208] In some embodiments, certain RNA (e.g., mRNA) compositions described herein may be selected for administration to Asian populations (e.g., Chinese populations), or in particular embodiments to older Asian populations (e.g., 60 years old or over, e.g., 60-85 or 65-85 years old).

[00209] In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to and/or assessed in subject(s) who have been determined not to show evidence of prior infection, and/or of present infection, before administration; in some embodiments, evidence of prior infection and/or of present infection, may be or include evidence of intact virus, or any viral nucleic acid, protein, lipid etc. present in the subject (e.g., in a biological sample thereof, such as blood, cells, mucus, and/or tissue), and/or evidence of a subject's immune response to the same. In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to and/or assessed in subject(s) who have been determined to show evidence of prior infection, and/or of present infection, before administration; in some embodiments, evidence of prior infection and/or of present infection, may be or include evidence of intact virus, or any viral nucleic acid, protein, lipid etc. present in the subject (e.g., in a biological sample thereof, such as blood, cells, mucus, and/or tissue), and/or evidence of a subject's immune response to the same. In some embodiments, a subject is considered to have a prior infection based on having a positive N-binding antibody test result or positive nucleic acid amplification test (NAAT) result on the day of Dose 1.

[00210] In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to a subject who has been informed of a risk of side effects that may include one or more of, for example: chills, fever, headache, injection site pain, muscle pain, tiredness; in some embodiments, an RNA (e.g., mRNA) composition is administered to a subject who has been invited to notify a healthcare provider if one or more such side effects occurs, is experienced as more than mild or moderate, persists for a period of more than a day or a few days, or if any serious or unexpected event is experienced that the subject reasonably considers may be associated with receipt of the composition. In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to a subject who has been invited to notify a healthcare provider of particular medical conditions which may include, for example, one or more of allergies, bleeding disorder or taking a blood thinner medication, breastfeeding, fever, immunocompromised state or taking medication that affects the immune system, pregnancy or plan to become pregnant, etc. In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to a subject who has been invited to notify a healthcare provider of having received another COVID-19 vaccine. In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to a subject not having one of the following medical conditions: experiencing febrile illness, receiving immunosuppressant therapy, receiving anticoagulant therapy, suffering from a bleeding disorder (e.g., one that would contraindicate intramuscular injection), or pregnancy and/or breastfeeding/lactation. In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to a subject not having received another COVID-19 vaccine. In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to a subject who has not had an allergic reaction to any component of the RNA (e.g., mRNA) composition. Examples of such allergic reaction may include, but are not limited to difficulty breathing, swelling of fact and/or throat, fast heartbeat, rash, dizziness and/or weakness. In some embodiments, an RNA (e.g., mRNA) composition as provided herein is administered to a subject who received a first dose and did not have an allergic reaction (e.g., as described herein) to the first dose. In some embodiments where allergic reaction occurs in subject(s) after receiving a dose of an RNA (e.g., mRNA) composition as provided herein, such subject(s) may be administered one or more interventions such as treatment to manage and/or reduce symptom(s) of such allergic reactions, for example, fever-reducing and/or anti-inflammatory agents.

[00211] In some embodiments, a subject who has received at least one dose of an RNA (e.g., mRNA) composition as provided herein is informed of avoiding being exposed to a coronavirus (e.g., SARS-CoV-2) unless and until several days (e.g., at least 7 days, at least 8 days, 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, etc.) have passed since administration of a second dose. For example, a subject who has received at least one dose of an RNA (e.g., mRNA) composition as provided herein is informed of taking precautionary measures against SARS-CoV-2 infection (e.g., remaining socially distant, wearing masks, frequent hand-washing, etc.) unless and until several days (e.g., at least 7 days, at least 8 days, 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, etc.) have passed since administration of a second dose. Accordingly, in some embodiments, methods of administering an RNA (e.g., mRNA) composition as provided herein comprise administering a second dose of such an RNA (e.g., mRNA) composition as provided herein to a subject who received a first dose and took precautionary measures to avoid being exposed to a coronavirus (e.g., SARS-CoV-2).

[00212] In some embodiments, RNA (e.g., mRNA) compositions described herein may be delivered to a draining lymph node of a subject in need thereof, for example, for vaccine priming. In some embodiments, such delivery may be performed by intramuscular administration of a provided RNA (e.g., mRNA) composition.

[00213] In some embodiments, different particular RNA (e.g., mRNA) compositions may be administered to different subject population(s); alternatively or additionally, in some embodiments, different dosing regimens may be administered to different subject populations. For example, in some embodiments, RNA (e.g., mRNA) compositions administered to particular subject population(s) may be characterized by one or more particular effects (e.g., incidence and/or degree of effect) in those subject populations. In some embodiments, such effect(s) may be or comprise, for example titer and/or persistence of neutralizing antibodies and/or T cells (e.g., THl-type T cells such as CD4+ and/or CD8+ T cells), protection against challenge (e.g., via injection and/or nasal exposure, etc), incidence, severity, and/or persistence of side effects (e.g., reactogenicity), etc.

[00214] In some embodiments, one or more RNA (e.g., mRNA) compositions described herein may be administered according to a regimen established to reduce COVID-19 incidence per 1000 person-years, e.g., based on a laboratory test such as nucleic acid amplification test (NAAT). In some embodiments, one or more RNA (e.g., mRNA) compositions described herein may be administered according to a regimen established to reduce COVID-19 incidence per 1000 person-years based on a laboratory test such as nucleic acid amplification test (NAAT) in subjects receiving at least one dose of a provided RNA (e.g., mRNA) composition with no serological or virological evidence (e.g., up to 7 days after receipt of the last dose) of past SARS-CoV-2 infection. In some embodiments, one or more RNA (e.g., mRNA) compositions described herein may be administered according to a regimen established to reduce confirmed severe COVID-19 incidence per 1000 person-years. In some embodiments, one or more RNA (e.g., mRNA) compositions described herein may be administered according to a regimen established to reduce confirmed severe COVID-19 incidence per 1000 person-years in subjects receiving at least one dose of a provided RNA (e.g., mRNA) composition with no serological or virological evidence of past SARS-CoV-2 infection.

[00215] In some embodiments, one or more RNA (e.g., mRNA) compositions described herein may be administered according to a regimen established to produce neutralizing antibodies directed to a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD) as measured in serum from a subject that achieves or exceeds a reference level (e.g., a reference level determined based on human SARS-CoV-2 infection/COVID-19 convalescent sera) for a period of time and/or induction of cell-mediated immune response (e.g., a T cell response against SARS-CoV-2), including, e.g., in some embodiments induction of T cells that recognize at least one or more MHC-restricted (e.g., MHC class I-restricted) epitopes within a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD) for a period of time. In some such embodiments, the period of time may be at least 2 months, 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months or longer. In some embodiments, one or more epitopes recognized by vaccine-induced T cells (e.g., CD8+ T cells) may be presented on a MHC class I allele that is present in at least 50% of subjects in a least 80%, at least 90%, or more; in some such HLA-A*2402, HLA-B*3501, HLA-B*4401, or HLA-

HLA-A*0201 YLQPRTFLL; HLA-A*0201 RLQSLQTYV; HLA-A*2402 QYIKWPWYI; HLA-A*2402 NYNYLYRLF; HLA-A*2402 KWPWYIWLGF; HLA-B*3501 QPTESIVRF; HLA- B*3501 IPFAMQMAY; or HLA-B*3501 LPFNDGVYF.

[00216] In some embodiments, efficacy is assessed as COVID-19 incidence per 1000 person-years in individuals without serological or virological evidence of past SARS-CoV-2 infection before and during vaccination regimen; alternatively or additionally, in some embodiments, efficacy is assessed as COVID-19 incidence per 1000 person-years in subjects with and without evidence of past SARS-CoV-2 infection before and during vaccination regimen. In some such embodiments, such incidence is of COVID-19 cases confirmed within a specific time period after the final vaccination dose (e.g., a first dose in a single-dose regimen; a second dose in a two-dose regimen, etc); in some embodiments, such time period may be within (i.e., up to and including 7 days) a particular number of days (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 days or more). In some embodiments, such time period may be within 7 days or within 14 days or within 21 days or within 28 days. In some embodiments, such time period may be within 7 days. In some embodiments, such time period may be within 14 days.

[00217] In some embodiments (e.g., in some embodiments of assessing efficacy), a subject is determined to have experienced COVID-19 infection if one or more of the following is established: detection of SARS-CoV-2 nucleic acid in a sample from the subject, detection of antibodies that specifically recognize SARS-CoV-2 (e.g., a SARS-Co-V-2 spike protein), one or more symptoms of COVID-19 infection, and combinations thereof. In some such embodiments, detection of SARS-CoV-2 nucleic acid may involve, for example, NAAT testing on a mid- turbinatae swap sample. In some such embodiments, detection of relevant antibodies may involve serological testing of a blood sample or portion thereof. In some such embodiments, symptoms of COVID-19 infection may be or include: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, vomiting and combinations thereof. In some such embodiments, symptoms of COVID-19 infection may be or include: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, vomiting, fatigue, headache, nasal congestion or runny nose, nausea, and combinations thereof. In some such embodiments, a subject is determined to have experienced COVID-19 infection if such subject both has experienced one such symptom and also has received a positive test for SARS-CoV-2 nucleic acid or antibodies, or both. In some such embodiments, a subject is determined to have experienced COVID-19 infection if such subject both has experienced one such symptom and also has received a positive test for SARS-CoV-2 nucleic acid. In some such embodiments, a subject is determined to have experienced COVID-19 infection if such subject both has experienced one such symptom and also has received a positive test for SARS-CoV-2 antibodies.

[00218] In some embodiments (e.g., in some embodiments of assessing efficacy), a subject is determined to have experienced severe COVID-19 infection if such subject has experienced one or more of: clinical signs at rest indicative or severe systemic illness (e.g., one or more of respiratory rate at greater than or equal to 30 breaths per minute, heart rate at or above 125 beats per minute, SpO2 less than or equal to 93% on room air at sea level or a PaO2/FiO2 below 300 m Hg), respiratory failure (e.g., one or more of needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, ECMO), evidence of shock (systolic blood pressure below 90 mm Hg, diastolic blood pressure below 60mm Hg, requiring vasopressors), significant acute renal, hepatic, or neurologic dysfunction, admission to an intensive care unit, death, and combinations thereof. [00219] In some embodiments, one or more RNA (e.g., mRNA) compositions described herein may be administered according to a regimen established to reduce the percentage of subjects reporting at least one of the following: (i) one or more local reactions (e.g., as described herein) for up to 7 days following each dose; (ii) one or more systemic events for up to 7 days following each dose; (iii) adverse events (e.g., as described herein) from a first dose to 1 month after the last dose; and/or (iv) serious adverse events (e.g., as described herein) from a first dose to 6 months after the last dose.

[00220] In some embodiments, one or more subjects who have received an RNA (e.g., mRNA) composition as described herein may be monitored (e.g., for a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 days or more, including, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 weeks or more, including for example 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 months or more, including for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 years or more) to assess, for example, presence of an immune response to component(s) of the administered composition, evidence of exposure to and/or immune response to SARS-CoV-2 or another coronavirus, evidence of any adverse event, etc. In some embodiments, monitoring may be via tele-visit.

Alternatively or additionally, in some embodiments, monitoring may be in-person.

[00221] In some embodiments, a treatment effect conferred by one or more RNA (e.g., mRNA) compositions described herein may be characterized by (i) a SARS-CoV-2 anti-Sl binding antibody level above a predetermined threshold; (ii) a SARS-CoV-2 anti-RBD binding antibody level above a pre-determined threshold; and/or (iii) a SARS-CoV-2 serum neutralizing titer above a threshold level, e.g., at baseline, 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, and/or 24 months after completion of vaccination. In some embodiments, anti-Sl binding antibody and/or anti-RBD binding antibody levels and/or serum neutralizing titers may be characterized by geometric mean concentration (GMC), geometric mean titer (GMT), or geometric mean fold-rise (GMFR).

[00222] In some embodiments, a treatment effect conferred by one or more RNA (e.g., mRNA) compositions described herein may be characterized in that percentage of treated subjects showing a SARS-CoV-2 serum neutralizing titer above a pre-determined threshold, e.g., at baseline, 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, and/or 24 months after completion of vaccination, is higher than the percentage of nontreated subjects showing a SARS-CoV-2 serum neutralizing titer above such a pre-determined threshold (e.g., as described herein). In some embodiments, a serum neutralizing titer may be characterized by geometric mean concentration (GMC), geometric mean titer (GMT), or geometric mean fold-rise (GMFR).

[00223] In some embodiments, a treatment effect conferred by one or more RNA (e.g., mRNA) compositions described herein may be characterized by detection of SARS-CoV-2 NVA-specific binding antibody.

[00224] In some embodiments, a treatment effect conferred by one or more RNA (e.g., mRNA) compositions described herein may be characterized by SARS-CoV-2 detection by nucleic acid amplification test.

[00225] In some embodiments, a treatment effect conferred by one or more RNA (e.g., mRNA) compositions described herein may be characterized by induction of cell-mediated immune response (e.g., a T cell response against SARS-CoV-2), including, e.g., in some embodiments induction of T cells that recognize at least one or more MHC-restricted (e.g., MHC class I-restricted) epitopes within a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD). In some embodiments, one or more epitopes recognized by vaccine- induced T cells (e.g., CD8+ T cells) may be presented on a MHC class I allele that is present in at least 50% of subjects in a population, including, e.g., at least 60%, at least 70%, at least 80%, at least 90%, or more; in some such embodiments, the MHC class I allele may be HLA-B*0702, HLA-A*2402, HLA-B*3501, HLA-B*4401, or HLA- A*0201. In some embodiments, an epitope may comprise HLA-A*0201 YLQPRTFLL; HLA-A*0201 RLQSLQTYV; HLA-A*2402 QYIKWPWYI; HLA-A*2402 NYNYLYRLF; HLA-A*2402 KWPWYIWLGF; HLA-B*3501 QPTESIVRF; HLA- B*3501 IPFAMQMAY; or HLA-B*3501 LPFNDGVYF.

[00226] In some embodiments, primary vaccine efficacy (VE) of one or more RNA (e.g., mRNA) compositions described herein may be established when there is sufficient evidence (posterior probability) that either primary VE1 or both primary VE1 and primary VE2 are >30% or higher (including, e.g., greater than 40%, greater than 50%, greater than 60%, greater than 70%, greater than 80%, greater than 90%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, or higher), wherein primary VE is defined as primary VE = 100 x (1 - IRR); and IRR is calculated as the ratio of COVID-19 illness rate in the vaccine group to the corresponding illness rate in the placebo group. Primary VE1 represents VE for prophylactic RNA (e.g., mRNA) compositions described herein against confirmed COVID-19 in participants without evidence of infection before vaccination, and primary VE2 represents VE for prophylactic RNA (e.g., mRNA) compositions described herein against confirmed COVID-19 in all participants after vaccination. In some embodiments, primary VE1 and VE2 can be evaluated sequentially to control the overall type I error of 2.5% (hierarchical testing). In some embodiments where one or more RNA (e.g., mRNA) compositions described herein are demonstrated to achieve primary VE endponts as discussed above, secondary VE endpoints (e.g., confirmed severe COVID-19 in participants without evidence of infection before vaccination and confirmed severe COVID-19 in all participants) can be evaluated sequentially, e.g., by the same method used for the primary VE endpoint evaluation (hierarchical testing) as discussed above. In some embodiments, evaluation of primary and/or secondary VE endpoints may be based on at least 20,000 or more subjects (e.g., at least 25,000 or more subjects) randomized in a 1: 1 ratio to the vaccine or placebo group, e.g., based on the following assumptions: (i) 1.0% illness rate per year in the placebo group, and (ii) 20% of the participants being non-evaluable or having serological evidence of prior infection with SARS- CoV-2, potentially making them immune to further infection.

[00227] In some embodiments, one or more RNA (e.g., mRNA) compositions described herein may be administered according to a regimen established to achieve maintenance and/or continued enhancement of an immune response. For example, in some embodiments, an administration regimen may include a first dose optionally followed by one or more subsequent doses; in some embodiments, need for, timing of, and/or magnitude of any such subsequent dose(s) may be selected to maintain, enhance, and/or modify one or more immune responses or features thereof. In some embodiments, number, timing, and/or amount(s) of dose(s) have been established to be effective when administered to a relevant population. In some embodiments, number, timing and/or amount(s) of dose(s) may be adjusted for an individual subject; for example, in some embodiments, one or more features of an immune response in an individual subject may be assessed at least once (and optionally more than once, for example multiple times, typically spaced apart, often at pre-selected intervals) after receipt of a first dose. For example, presence of antibodies, B cells, and/or T cells (e.g., CD4+ and/or CD8+ T cells), and/or of cytokines secreted thereby and/or identity of and/or extent of responses to particular antigen(s) and/or epitope(s) may be assessed. In some embodiments, need for, timing of, and/or amount of a subsequent dose may be determined in light of such assessments.

[00228] As noted hereinabove, in some embodiments, one or more subjects who have received an RNA (e.g., mRNA) composition as described herein may be monitored (e.g., for a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 days or more, including, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 weeks or more, including for example 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 months or more, including for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 years or more) from receipt of any particular dose to assess, for example, presence of an immune response to component(s) of the administered composition, evidence of exposure to and/or immune response to SARS-CoV-2 or another coronavirus, evidence of any adverse event, etc, including to perform assessment of one or more of presence of antibodies, B cells, and/or T cells (e.g., CD4+ and/or CD8+ T cells), and/or of cytokines secreted thereby and/or identity of and/or extent of responses to particular antigen(s) and/or epitope(s) may be assessed. Administration of a composition as described herein may be in accordance with a regimen that includes one or more such monitoring steps.

[00229] For example, in some embodiments, need for, timing of, and/or amount of a second dose relative to a first dose (and/or of a subsequent dose relative to a prior dose) is assessed, determined, and/or selected such that administration of such second (or subsequent) dose achieves amplification or modification of an immune response (e.g., as described herein) observed after the first (or other prior) dose. In some embodiments, such amplification of an immune response (e.g., ones described herein) may be at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or higher, as compared to the level of an immune response observed after the first dose. In some embodiments, such amplification of an immune response may be at least 1.5 fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, at least 20-fold, at least 30-fold, or higher, as compared to the level of an immune response observed after the first dose.

[00230] In some embodiments, need for, timing of, and/or amount of a second (or subsequent) dose relative to a first (or other prior) dose is assessed, determined, and/or selected such that administration of the later dose extends the durability of an immune response (e.g., as described herein) observed after the earlier dose; in some such embodiments, the durability may be extended by at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, or longer. In some embodiments, an immune response observed after the first dose may be characterized by production of neutralizing antibodies directed to a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD) as measured in serum from a subject and/or induction of cell-mediated immune response (e.g., a T cell response against SARS-CoV-2), including, e.g., in some embodiments induction of T cells that recognize at least one or more MHC-restricted (e.g., MHC class I-restricted) epitopes within a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD). In some embodiments, one or more epitopes recognized by vaccine-induced T cells (e.g., CD8+ T cells) may be presented on a MHC class I allele that is present in at least 50% of subjects in a population, including, e.g., at least 60%, at least 70%, at least 80%, at least 90%, or more; in some such embodiments, the MHC class I allele may be HLA-B*0702, HLA-A*2402, HLA-B*3501, HLA-B*4401, or HLA- A*0201. In some embodiments, an epitope may comprise HLA-A*0201 YLQPRTFLL; HLA-A*0201 RLQSLQTYV;

HLA-A*2402 QYIKWPWYI; HLA-A*2402 NYNYLYRLF; HLA-A*2402 KWPWYIWLGF; HLA-B*3501 QPTESIVRF; HLA- B*3501 IPFAMQMAY; or HLA-B*3501 LPFNDGVYF.

[00231] In some embodiments, need for, timing of, and/or amount of a second dose relative to a first dose (or other subsequent dose relative to a prior dose) is assessed, determined and/or selected such that administration of such second (or subsequent) dose maintains or exceeds a reference level of an immune response; in some such embodiments, the reference level is determined based on human SARS-CoV-2 infection/COVID-19 convalescent sera and/or PBMC samples drawn from subjects (e.g., at least a period of time such as at least 14 days or longer, including, e.g., 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 25 days, 30 days, 35 days, 40 days, 45 days, 50 days, 55 days, 60 days, or longer, after PCR-confirmed diagnosis when the subjects were asymptomatic. In some embodiments, an immune response may be characterized by production of neutralizing antibodies directed to a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD) as measured in serum from a subject and/or induction of cell-mediated immune response (e.g., a T cell response against SARS-CoV-2), including, e.g., in some embodiments induction of T cells that recognize at least one or more MHC-restricted (e.g., MHC class I-restricted) epitopes within a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD). In some embodiments, one or more epitopes recognized by vaccine-induced T cells (e.g., CD8+ T cells) may be presented on a MHC class I allele that is present in at least 50% of subjects in a population, including, e.g., at least 60%, at least 70%, at least 80%, at least 90%, or more; in some such embodiments, the MHC class I allele may be HLA-B*0702, HLA-A*2402, HLA- B*3501, HLA-B*4401, or HLA-A*0201. In some embodiments, an epitope may comprise HLA-A*0201 YLQPRTFLL; HLA-A*0201 RLQSLQTYV; HLA-A*2402 QYIKWPWYI; HLA-A*2402 NYNYLYRLF; HLA-A*2402 KWPWYIWLGF; HLA-B*3501 QPTESIVRF; HLA-B*3501 IPFAMQMAY; or HU\-B*3501 LPFNDGVYF.

[00232] In some embodiments, determination of need for, timing of, and/or amount of a second (or subsequent) dose may include one or more steps of assessing, after (e.g., 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 days or longer after) a first (or other prior) dose, presence and/or expression levels of neutralizing antibodies directed to a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD) as measured in serum from a subject and/or induction of cell-mediated immune response (e.g., a T cell response against SARS-CoV-2), including, e.g., in some embodiments induction of T cells that recognize at least one or more MHC-restricted (e.g., MHC class I-restricted) epitopes within a SARS-CoV-2 spike polypeptide and/or an immunogenic fragment thereof (e.g., RBD). In some embodiments, one or more epitopes recognized by vaccine- induced T cells (e.g., CD8+ T cells) may be presented on a MHC class I allele that is present in at least 50% of subjects in a population, including, e.g., at least 60%, at least 70%, at least 80%, at least 90%, or more; in some such embodiments, the MHC class I allele may be HLA-B*0702, HLA-A*2402, HLA-B*3501, HLA-B*4401, or HLA- A*0201. In some embodiments, an epitope may comprise HLA-A*0201 YLQPRTFLL; HLA-A*0201 RLQSLQTYV; HLA-A*2402 QYIKWPWYI; HLA-A*2402 NYNYLYRLF; HLA-A*2402 KWPWYIWLGF; HLA-B*3501 QPTESIVRF; HLA- B*3501 IPFAMQMAY; or HLA-B*3501 LPFNDGVYF.

[00233] In some embodiments, a kit as provided herein may comprise a real-time monitoring logging device, which, for example in some embodiments, is capable of providing shipment temperatures, shipment time and/or location.

[00234] In some embodiments, an RNA (e.g., mRNA) composition as described herein may be shipped, stored, and/or utilized, in a container (such as a vial or syringe), e.g., a glass container (such as a glass vial or syringe), which, in some embodiments, may be a single-dose container or a multi-dose container (e.g., may be arranged and constructed to hold, and/or in some embodiments may hold, a single dose, or multiple doses of a product for administration). In some embodiments, a multi-dose container (such as a multi-dose vial or syringe) may be arranged and constructed to hold, and/or may hold 2, 3, 4, 5, 6, 7, 8, 9, 10 or more doses; in some particular embodiments, it may be designed to hold and/or may hold 5 doses. In some embodiments, a singledose or multi-dose container (such as a single-dose or multi-dose vial or syringe) may be arranged and constructed to hold and/or may hold a volume or amount greater than the indicated number of doses, e.g., in order to permit some loss in transfer and/or administration. In some embodiments, an RNA (e.g., mRNA) composition as described herein may be shipped, stored, and/or utilized, in a preservative-free glass container (e.g., a preservative-free glass vial or syringe, e.g., a single-dose or multi-dose preservative-free glass vial or syringe). In some embodiments, an RNA (e.g., mRNA) composition as described herein may be shipped, stored, and/or utilized, in a preservative-free glass container (e.g., a preservative-free glass vial or syringe, e.g., a singledose or multi-dose preservative-free glass vial or syringe) that contains a frozen liquid, e.g., in some embodiments 0.45 ml of frozen liquid (e.g., including 5 doses). In some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a vial or syringe) in which it is disposed, is shipped, stored, and/or utilized may be maintained at a temperature below room temperature, at or below 4 °C, at or below 0 °C, at or below -20 °C, at or below -60 °C, at or below -70 °C, at or below -80 °C , at or below -90 °C, etc. In some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a viral or syringe) in which it is disposed, is shipped, stored, and/or utilized may be maintained at a temperature between -80°C and -60°C and in some embodiments protected from light. In some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a viral or syringe) in which it is disposed, is shipped, stored, and/or utilized may be maintained at a temperature below about 25oC, and in some embodiments protected from light. In some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a viral or syringe) in which it is disposed, is shipped, stored, and/or utilized may be maintained at a temperature below about 5oC (e.g., below about 4oC), and in some embodiments protected from light. In some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a viral or syringe) in which it is disposed, is shipped, stored, and/or utilized may be maintained at a temperature below about -20oC, and in some embodiments protected from light. In some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a viral or syringe) in which it is disposed, is shipped, stored, and/or utilized may be maintained at a temperature above about -60oC (e.g., in some embodiments at or above about -20oC, and in some embodiments at or above about 4-5oC, in either case optionally below about 25oC), and in some embodiments protected from light, or otherwise without affirmative steps (e.g., cooling measures) taken to achieve a storage temperature materially below about -20oC.

[00235] In some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a vial or syringe) in which it is disposed is shipped, stored, and/or utilized together with and/or in the context of a thermally protective material or container and/or of a temperature adjusting material. For example, in some embodiments, an RNA (e.g., mRNA) composition as described herein and/or a container (e.g., a vial or syringe) in which it is disposed is shipped, stored, and/or utilized together with ice and/or dry ice and/or with an insulating material. In some particular embodiments, a container (e.g., a vial or syringe) in which an RNA (e.g., mRNA) composition is disposed is positioned in a tray or other retaining device and is further contacted with (or otherwise in the presence of) temperature adjusting (e.g., ice and/or dry ice) material and/or insulating material. In some embodiments, multiple containers (e.g., multiple vials or syringes such as single use or multi-use vials or syringes as described herein) in which a provided RNA (e.g., mRNA) composition is disposed are co-localized (e.g., in a common tray, rack, box, etc.) and packaged with (or otherwise in the presence of) temperature adjusting (e.g., ice and/or dry ice) material and/or insulating material. To give but one example, in some embodiments, multiple containers (e.g., multiple vials or syringes such as single use or multi-use vials or syringes as described herein) in which an RNA (e.g., mRNA) composition is disposed are positioned in a common tray or rack, and multiple such trays or racks are stacked in a carton that is surrounded by a temperature adjusting material (e.g., dry ice) in a thermal (e.g., insulated) shipper. In some embodiments, temperature adjusting material is replenished periodically (e.g., within 24 hours of arrival at a site, and/or every 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, etc.). Preferably, re-entry into a thermal shipper should be infrequent, and desirably should not occur more than twice a day. In some embodiments, a thermal shipper is reclosed within 5, 4, 3, 2, or 1 minute, or less, of having been opened. In some embodiments, a provided RNA (e.g., mRNA) composition that has been stored within a thermal shipper for a period of time, optionally within a particular temperature range remains useful. For example, in some embodiments, if a thermal shipper as described herein containing a provided RNA (e.g., mRNA) composition is or has been maintained (e.g., stored) at a temperature within a range of about 15 °C to about 25 °C, the RNA (e.g., mRNA) composition may be used for up to 10 days; that is, in some embodiments, a provided RNA (e.g., mRNA) composition that has been maintained within a thermal shipper, which thermal shipper is at a temperature within a range of about 15 °C to about 25 °C, for a period of not more than 10 days is administered to a subject. Alternatively or additionally, in some embodiments, if a provided RNA (e.g., mRNA) composition is or has been maintained (e.g., stored) within a thermal shipper, which thermal shipper has been maintained (e.g., stored) at a temperature within a range of about 15 °C to about 25 °C, it may be used for up to 10 days; that is, in some embodiments, a provided RNA (e.g., mRNA) composition that has been maintained within a thermal shipper, which thermal shipper has been maintained at a temperature within a range of about 15 °C to about 25 °C for a period of not more than 10 days is administered to a subject.

[00236] In some embodiments, a syringe is a prefilled syringe. In some embodiments, a prefilled syringe is a glass or plastic syringe. Suitable syringes include e.g., those described in Makwana, Sagar, et al. "Prefilled syringes: an innovation in parenteral packaging." International journal of pharmaceutical investigation 1.4 (2011): 200; Sacha, Gregory, J. Aaron Rogers, and Reagan L. Miller. "Pre-filled syringes: a review of the history, manufacturing and challenges." Pharmaceutical development and technology 20.1 (2015): 1-11; and Borse, Sandip Arun, Ashish Prakash Gorle, and Kuldip Patil. "Prefilled syringe: A review of injectable dosage form delivery system." Int. J. Pharm. Sci. Res 11 (2020): 167-174, the contents of each of which is incorporated by reference herein in their entirety.

[00237] In some embodiments, a composition described herein is administered a volume of about 0.1 to 5.0 ml. In some embodiments, a composition described herein is administered a volume of about 0.1 to 1.0 ml. In some embodiments, a composition described herein is administered a volume of about 0.1 to 0.50 ml. In some embodiments, a composition described herein is administered in a volume of about 100 pL to about 300 μL. In some embodiments, a composition described herein is administered in a volume of about 50 pL to about 300 μL. In some embodiments, a composition described herein is administered in a volume of about 50 pL to about 200 pL. In some embodiments, a composition described herein is administered in a volume of about 100 pL to about 300μL. In some embodiments, a composition described herein is administered in a volume of about 200 pL to about 300μL. In some embodiments, a composition described herein is administered in a volume of about 50 pL to about 500 μL. In some embodiments, a composition described herein is administered in a volume of about 50 pL, about 100 pL, about 150 pL, about 200 pL, about 250 pL, about 300 pL, about 350 pL, about 400 pL, about 450 pL, or about 500 μL.

[00238] In some embodiments, a provided RNA (e.g., mRNA) composition is shipped and/or stored in a frozen state. In some embodiments, a provided RNA (e.g., mRNA composition is shipped and/or stored as a frozen suspension, which in some embodiments does not contain preservative. In some embodiments, a frozen RNA (e.g., mRNA) composition is thawed. In some embodiments, a thawed RNA (e.g., mRNA) composition (e.g., a suspension) may contain white to off-white opaque amorphous particles. In some embodiments, a thawed RNA (e.g., mRNA) composition may be used for up to a small number (e.g., 1, 2, 3, 4, 5, or 6) of days after thawing if maintained (e.g., stored) at a temperature at or below room temperature (e.g., below about 30 °C, 25 °C, 20 °C, 15 °C, 10 °C, 8 °C, 4 °C, etc). In some embodiments, a thawed RNA (e.g., mRNA) composition may be used after being stored (e.g., for such small number of days) at a temperature between about 2 °C and about 8 °C; alternatively or additionally, a thawed RNA (e.g., mRNA) composition may be used within a small number (e.g., 1, 2, 3, 4, 5, 6) of hours after thawing at room temperature. Thus, in some embodiments, a provided RNA (e.g., mRNA) composition that has been thawed and maintained at a temperature at or below room temperature, and in some embodiments between about 2 °C and about 8 °C, for not more than 6, 5, 4, 3, 2, or 1 days is administered to a subject. Alternatively or additionally, in some embodiments, a provided RNA (e.g., mRNA) composition that has been thawed and maintained at room temperature for not more than 6, 5, 4, 3, 2, or 1 hours is administered to a subject. In some embodiments, a provided RNA (e.g., mRNA) composition is shipped and/or stored in a concentrated state. In some embodiments, such a concentrated composition is diluted prior to administration. In some embodiments, a diluted composition is administered within a period of about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 hour(s) post-dilution; in some embodiments, such administration is within 6 hours post-dilution. Thus, in some embodiments, diluted preparation of a provided RNA (e.g., mRNA) composition is administered to a subject within 6 hours post-dilution (e.g., as described herein after having been maintained at an appropriate temperature, e.g., at a temperature below room temperature, at or below 4 °C, at or below 0 °C, at or below -20 °C, at or below -60 °C, at or below -70 °C, at or below - 80 °C, etc, and typically at or above about 2 °C, for example between about 2 °C and about 8 °C or between about 2 °C and about 25 °C). In some embodiments, unused composition is discarded within several hours (e.g., about 10, about 9, about 8, about 7, about 6, about 5 or fewer hours) after dilution; in some embodiments, unused composition is discarded within 6 hours of dilution. [00239] In some embodiments, an RNA (e.g., mRNA) composition that is stored, shipped or utilized (e.g., a frozen composition, a liquid concentrated composition, a diluted liquid composition, etc.) may have been maintained at a temperature materially above -60oC for a period of time of at least 1, 2, 3, 4, 5, 6, 7 days or more, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 weeks or more, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months or more; in some such embodiments, such composition may have been maintained at a temperature at or above about -20oC for such period of time, and/or at a temperature up to or about 4-5oC for such period of time, and/or may have been maintained at a temperature above about 4-5oC, and optionally about 25oC for a period of time up that is less than two (2) months and/or optionally up to about one (1) month. In some embodiments, such composition may not have been stored, shipped or utilized (or otherwise exposed to) a temperature materially above about 4-5oC, and in particular not at or near a temperature of about 25oC for a period of time as long as about 2 weeks, or in some embodiments 1 week. In some embodiments, such composition may not have been stored, shipped or utilized (or otherwise exposed to) a temperature materially above about -20oC, and in particular not at or near a temperature of about 4-5oC for a period of time as long as about 12 months, 11 months, 10 months, 9 months, 8 months, 7 months, 6 months, 5 months, 4 months, 3 months, 2 months, or, in some embodiments, for a period of time as long as about 8 weeks or 6 weeks or materially more than about 2 months or, in some embodiments, 3 months or, in some embodiments 4 months.

[00240] In some embodiments, an RNA (e.g., mRNA) composition that is stored, shipped or utilized (e.g., a frozen composition, a liquid concentrated composition, a diluted liquid composition, etc.) may be protected from light. In some embodiments, one or more steps may be taken to reduce or minimize exposure to light for such compositions (e.g., which may be disposed within a container such as a vial or a syringe). In some embodiments, exposure to direct sunlight and/or to ultraviolent light is avoided. In some embodiments, a diluted solution may be handled and/or utilized under normal room light conditions (e.g., without particular steps taken to minimize or reduce exposure to room light). It should be understood that strict adherence to aseptic techniques is desirable during handling (e.g., diluting and/or administration) of an RNA (e.g., mRNA) composition as described herein. In some embodiments, an RNA (e.g., mRNA) composition as described herein is not administered (e.g., is not injected) intravenously. In some embodiments, an RNA (e.g., mRNA) composition as described herein is not administered (e.g., is not injected) intradermally. In some embodiments, an RNA (e.g., mRNA) composition as described herein is not administered (e.g., is not injected) subcutaneously. In some embodiments, an RNA (e.g., mRNA) composition as described herein is not administered (e.g., is not injected) any of intravenously, intradermally, or subcutaneously. In some embodiments, an RNA (e.g., mRNA) composition as described herein is not administered to a subject with a known hypersensitivity to any ingredient thereof. In some embodiments, a subject to whom an RNA (e.g., mRNA) composition has been administered is monitored for one or more signs of anaphylaxis. In some embodiments, a subject to whom an RNA (e.g., mRNA) composition is administered had previously received at least one dose of a different vaccine for SARS-CoV-2; in some embodiments, a subject to whom an RNA (e.g., mRNA) composition is administered had not previously received a different vaccine for SARS- CoV-2. In some embodiments, a subject's temperature is taken promptly prior to administration of an RNA (e.g., mRNA) composition (e.g., shortly before or after thawing, dilution, and/or administration of such composition); in some embodiments, if such subject is determined to be febrile, administration is delayed or canceled. In some embodiments, an RNA (e.g., mRNA) composition as described herein is not administered to a subject who is receiving anticoagulant therapy or is suffering from or susceptible to a bleeding disorder or condition that would contraindicate intramuscular injection. In some embodiments, an RNA (e.g., mRNA) composition as described herein is administered by a healthcare professional who has communicated with the subject receiving the composition information relating to side effects and risks. In some embodiments, an RNA (e.g., mRNA) composition as described herein is administered by a healthcare professional who has agreed to submit an adverse event report for any serious adverse events, which may include for example one or more of death, development of a disability or congenital anomaly/birth defect (e.g., in a child of the subject), in-patient hospitalization (including prolongation of an existing hospitalization), a life-threatening event, a medical or surgical intervention to prevent death, a persistent or significant or substantial disruption of the ability to conduct normal life functions; or another important medical event that may jeopardize the individual and may require medical or surgical intervention (treatment) to prevent one of the other outcomes.

[00241] In some embodiments, provided RNA compositions are administered to a population of individuals under 18 years of age, or under 17 years of age, or under 16 years of age, or under 15 years of age, or under 14 years of age, or under 13 years of age, for example according to a regimen established to have a rate of incidence for one or more of the local reaction events indicated below that does not exceed the rate of incidence indicated below: pain at the injection site (75% after a first dose and/or a second dose, and/or a lower incidence after a second dose, e.g., 65% after a second dose); redness at the injection site (less than 5% after a first dose and/or a second dose); and/or swelling at the injection site (less than 5% after a first dose and/or a second dose).

[00242] In some embodiments, provided RNA compositions are administered to a population of individuals under 18 years of age, or under 17 years of age, or under 16 years of age, or under 15 years of age, or under 14 years of age, or under 13 years of age, for example according to a regimen established to have a rate of incidence for one or more of the systemic reaction events indicated below that does not exceed the rate of incidence indicated below: fatigue (55% after a first dose and/or a second dose); headache (50% after a first dose and/or a second dose); muscle pain (40% after a first dose and/or a second dose); chills (40% after a first dose and/or a second dose); joint pain (20% after a first dose and/or a second dose); fever (25% after a first dose and/or a second dose); vomiting (10% after a first dose and/or a second dose); and/or diarrhea (10% after a first dose and/or a second dose).

[00243] In some embodiments, medication that alleviates one or more symptoms of one or more local reaction and/or systemic reaction events (e.g., described herein) are administered to individuals under 18 years of age, or under 17 years of age, or under 16 years of age, or under 15 years of age, or under 14 years of age, or under 13 years of age who have been administered with provided RNA compositions and have experienced one or more of the local and/or systemic reaction events (e.g., described herein). In some embodiments, antipyretic and/or pain medication can be administered to such individuals.

[00244] Among other things, the present disclosure describes an RNA comprising a nucleotide sequence encoding a polypeptide comprising an S2 domain, or a fragment thereoof.

[00245] In some embodiments, an S2 domain comprises amino acids 686-1213 of SEQ ID NO: 1, 686-1211 of SEQ ID NO: 1, amino acids 687-1206 of SEQ ID NO: 1, or amino acids 687-1211 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant, optionally wherein the S2 domain compries one or more mutations that stabilize the S2 domain (e.g., stabilize the prefusion conformation of the S2 domain).

[00246] In some embodiments, an S2 domain comprises: an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYH LMSFPQSAPHGWFLHVTYVPAQEKN FTTAPAICH DG KAH FPREGVFVSNGTHWFVTQRN FYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIKWP, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto; an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYH LMSFPQSAPHGWFLHVTYVPAQEKN FTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRN FYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto; an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto. an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYH LM SFPQSAPHG WFLHVTYVPAQEKN FTTAPAICH DGKAH FPREGVFVSNGTHWFVTQRN FYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKY, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[00247] In some embodiments, an S2 domain or a fragment thereof comprises a stem helix and/or a fusion peptide of an S2 domain.

[00248] In some embodiments, a fusion peptide comprises a sequence of PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto, and the stem helix comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[00249] In some embodiments, an S2 domain comprises one or more stabilizing mutations.

[00250] In some embodiments, one or more stabilizing mutations comprise one or more mutations that can stabilize the prefusion confirmation of an S protein.

[00251] In some embodiments, one or more stabilizing mutations include one or more Pro substitutions.

[00252] In some embodiments, an S2 domain comprises one or more of the following mutations relative to

SEQ ID NO: 1, or corresponding mutation(s) in an S2 domain of an S protein of a SARS-CoV-2 variant:

(a) K986P and V987P;

(b) A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P;

(c) F817P, A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P; or

(d) any combination of (a)-(c).

[00253] In some embodiments, an S2 domain comprises one or more mutations that can result in the formation of a disulfide bond.

[00254] In some embodiments, an S2 domain comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S2 domain of a SARS-CoV-2 variant:

(a) V707C and T883C;

(b) I770C and A1015C;

(c) V826C and A1015C;

(d) V826C and L948C;

(e) F970C and G999C;

(f) S735C and T859C; or

(g) any combination of (a)-(e). [00255] In some embodiments, an S2 domain comprises one or more of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S protein of a SARS-CoV-2 variant:

(a) V707C, T883C, F970C, and G999C;

(b) S735C, T859C, I770C, and A1015C;

(c) S735C, T859C, V826C, and L948C;

(d) I770C, A1015C, V826C, and L948C;

(e) S735C, I770C, A1015C, V826C, and L948C; or

(f) any combination of (a)-(e).

[00256] In some embodiments, an S2 domain comprises one or more Pro substitions and one or more mutations that can lead to the formation of a disulfide bond.

[00257] In some embodiments, an S2 domain comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresonding combination of mutations of an S2 domain of a SARS-CoV-2 variant:

A892P, A899P, 941, K986P, V987P, G999C, and I770C;

A892P, A899P, A942P, V987P, V707C, T883C, optionally wherein the S2 domain compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

A892P, A899P, A942P, V987P, V707C, T883C, F970C, G999C, optionally wherein the S2 domain compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1.

[00258] In some embodiments, an the S2 domain comprises one or more mutations that can prevent or result in the reduction of cleavage at the S2' cleavage site.

[00259] In some embodiments, an S2 domain comprises one or more mutations that can remove the S2' protease cleavage site.

[00260] In some embodiments, an S2 domain comprises one or more mutations at positions corresponding to amino acids 814 and/or 815 of SEQ ID NO: 1, optionally wherein the one or more mutations are a Gly, Ser, or Ala substition (e.g., a Gly substition).

[00261] In some embodiments, an S2 domain comprises Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1.

[00262] In some embodiments, an S2 domain comprises one or more Pro substitutions that can stabilize the S2 domain and one or more mutations that disrupt the S2' protease cleavage site.

[00263] In some embodiments, an S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1: A892P, A899P, A942P, K986P, V987P, or any combination thereof, or corresponding mutations in a SARS-Cov-2 variant, and a Gly substituion at positions 814 and/or 815 of SEQ ID NO: 1.

[00264] In some embodiments, an S2 domain comprises one or more substitutions of a hydrophillic amino acid for a hydrophobic amino acid, wherein the one or more hydrophobic amino acids are at positions that are solvent explosed in the S2 domain.

[00265] In some embodiments, an S2 domain comprises a substitution of a hydrophillic amino acid at one or more positions corresponding to amino acid 855, 861, 864, 976, or 984 of SEQ ID NO: 1, or any combination thereof.

[00266] In some embodiments, an S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1 F855S, L861E, L864D, V976D, and L984Q, or any combination thereof, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant. [00267] In some embodiments, an S2 domain comprises an amino acid substitution at one or more of the amino acids at positions 901, 1020, 1058, or any combination thereof relative to SEQ ID NO: 1, or corresponding substitutions in an S2 domain of a SARS-CoV-2 variant.

[00268] In some embodiments, an S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1: Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

[00269] In some embodiments, an S2 domain comprises:

(a) one or more of the following mutations: S375C, T859C, Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1, Pro substitutions at positions corresponding to amino acids K986P and/or V987P of SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(b) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, and Pro substiutions at positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1, wherein mutations are shown relative to SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(c) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1; or

(d) any combination of (a)-(c).

[00270] In some embodiments, an S2 domain comprises one or more subsitions of a hydrophobic residue for a hydrophillic residue at one or more positions that are solvent buried in the context of the full length S protein, but which are solvent exposed in the absense of the SI domain.

[00271] In some embodiments, one or more hydrophic residues include F855S, L861E, L864D, V976D, and L984Q, where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

[00272] In some embodiments, an S2 domain comprises one or more of the following mutations: L861E, L864D, V976D, and L984Q, a Pro substitution at one or more positions corresponding to amino acids F817P, A892P, A899P, A942P, or combinations thereof of SEQ ID NO: 1, optionally in combination with a Pro substitution at one or both positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1; or where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

[00273] In some embodiments, a polypeptide comprises a multimerization domain, optionally wherein the multimerization domain is a T4 fibritin domain.

[00274] In some embodiments, a multimerization domain is at the C-terminus of the polypeptide.

[00275] In some embodiments, a polypeptide does not comprise a transmembrane domain.

[00276] In some embodiments, a polypeptide comprises a transmembrane domain, optionally where the transmembrane domain is a SARS-CoV-2 transmembrane domain (e.g., a transmembrane domain comprising an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCC, or a variant thereof, including e.g., an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC, or a variant thereof).

[00277] In some embodiments, a polypeptide comprises a multimerization domain, and wherein the polypeptide does not comprise a transmembrane domain. [00278] In some embodiments, a polypeptide comprises a multimerization domain and a transmembrane domain, optionally wherein the multimerization domain is C-terminal to the S2 domain and the transmembrane domain is C-terminal to the trimerization domain.

[00279] In some embodiments, a multimerization domain is a trimerization domain (e.g., a fibritin domain, including, e.g., a peptide having an amino acid sequence of GYIPEAPRDGQAYVRKDGEWVLLSTFL, or a variant thereof) and/or wherein the tramsmembrane domain is a transmembrane domain of a SARS-CoV-2 S protein (e.g., a transmembrane domain comprising an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCC, or a variant thereof, including e.g., an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC, or a variant thereof).

[00280] In some embodiments, a polypeptide comprises a secretory signal peptide (e.g., a secretory signal peptide of a viral protein), optionally wherein the secretory signal peptide is at the N-terminus of the polypeptide. [00281] In some embodiments, a secretory signal peptide is a secretory signal peptide of a SARS-CoV-2 S protein (e.g., wherein the secretory signal peptide comprises amino acids 1-19 of SEQ ID NO: 1, or a an amino acid sequence of a correseponding region of an S protein of a SARS-CoV-2 variant).

[00282] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 178.

[00283] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 179.

[00284] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 180.

[00285] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 181.

[00286] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 182.

[00287] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 183.

[00288] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 184.

[00289] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 185.

[00290] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 186. [00291] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 187.

[00292] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 192.

[00293] In some embodiments, an RNA comprises a nuceltide sequence encoding polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 193.

[00294] In some embodiments, an RNA comprises a nuceltide sequence encoding polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 194.

[00295] In some embodiments, an RNA comprises a nuceltide sequence encoding a polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 195.

[00296] In some embodiments, an RNA comprises a nuceltide sequence encoding a polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 196.

[00297] In some embodiments, an RNA comprises a nuceltide sequence encoding a polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 197.

[00298] In some embodiments, an RNA comprises a nuceltide sequence encoding a polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 198.

[00299] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 446 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 446; (ii) the nucleotide sequence of SEQ ID NO: 447 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 447; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 183, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 183.

[00300] In some embodiments, an RNA comprises RNA comprises (i) the nucleotide sequence of SEQ ID NO: 448 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 448; (ii) the nucleotide sequence of SEQ ID NO: 449 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 449; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 184, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 184.

[00301] In some embodiments, an RNA comprises RNA comprises (i) the nucleotide sequence of SEQ ID NO: 450 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 450; (ii) the nucleotide sequence of SEQ ID NO: 451 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 451; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 185, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 185.

[00302] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 452 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 452; (ii) the nucleotide sequence of SEQ ID NO: 453 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 453; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 442, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 442.

[00303] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 455 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 455; (ii) the nucleotide sequence of SEQ ID NO: 456 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 456; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 443, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 443.

[00304] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 457 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 457; (ii) the nucleotide sequence of SEQ ID NO: 458 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 458; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 195, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 195.

[00305] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 459 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 459; (ii) the nucleotide sequence of SEQ ID NO: 460 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 460; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 197, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 197.

[00306] Among other things, the present disclosure comprising an RNA comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises an S2 domain or an immunogenic fragment thereof, and a Receptor Binding Domain of a SARS-CoV-2 S protein.

[00307] In some embodiments, an S2 domain and an RBD are connected by a non-endogenous sequence.

[00308] In some embodiments, an S2 domain is N-terminal or C-terminal to the RBD.

[00309] In some embodiments, a polypeptide does not comprise an NTD.

[00310] In some embodiments, an RBD is directly linked to the S2 domain.

[00311] In some embodiments, an RBD is connected to the S2 domain via a linker sequence.

[00312] In some embodiments, a linker sequence is a flexible linker sequence, a helical linker sequence, or a rigid linker sequence.

[00313] In some embodimetns, a linker sequence comprises a protease recognition site. [00314] In some embodiments, a linker sequence comprises a furin recognition site (e.g., an amino acid sequence of AGNRVRRSVG, or an amino acid with 1, 2, 3, 4, or more mutations thereto).

[00315] In some embodiments, an RNA encodes a polypeptide comprising one or more multimerization domains (e.g., two or mmore multimerization domains).

[00316] In some embodiments, a multimerization domain (e.g., a fibritin domain is attached to each of the S2 polyeptpide and the RBD, and the RBD and the S2 domain are connected via a linker that comprises a protease cleavage site, and the polypeptide is configured such that, upon cleavage of the furin cleavage site, a fibritin domain is attached to each of the S2 domain and the RBD.

[00317] In some embodiments, an RNA encodes a polypeptide comprising a transmembrane domain, an RBD, and an S2 domain (e.g., a transmembrane domain comprising EQYIKWPWYIWLGFIAGLIAIVMVTIMLCC, or a variant thereof, including, e.g., EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC), and the polypeptide is configured such that, upon cleavage, one of the RBD and the S2 domain is membrane bound and the other is soluble. In some embodiments, the polypeptide is configured such that the RBD is membrane bound and the S2 domain is soluble. In some embodiments, the S2 is N-terminal to the RBD. In some embodiments, a transmembrane domain is C-terminal to the RBD. In some embodiments, a multimerization domain is attached to each of the S2 and the RBD, wherein each of the fibritin domains is C-terminal to the S2 and the RBD.

[00318] In some embodiments, a polypeptide comprises a fibritin domain directly linked to the C-terminus of the S2 domain, a fibritin domain is directly linked to the C-terminus of the RBD, the S2 is N-terminal to the RBD, a transmembrane domain is linked to the C-terminus of the fibritin domain that is at the C-terminus of the RBD, and wherein a linker sequence is located between the fibritin domain that is attached to the C-terminus of the S2 domain, and the RBD.

[00319] In some embodiments, an RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

[00320] In some embodiments, an S2 domain comprises amino acid 686-1213 of SEQ ID NO: 1, 686-1211 of SEQ ID NO: 1, amino acids 687-1206 of SEQ ID NO: 1, or amino acids 687-1211 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant, optionally wherein the S2 domain comprises one or more mutations that stabilize the S2 domain.

[00321] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 462 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 462; (ii) the nucleotide sequence of SEQ ID NO: 463 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 463; and/or (Hi) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 188, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 188.

[00322] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 469 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 469; (ii) the nucleotide sequence of SEQ ID NO: 470 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 470; and/or (Hi) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 444, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 444. [00323] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 471 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 471; (ii) the nucleotide sequence of SEQ ID NO: 472 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 472; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 445, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 445.

[00324] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide, where the polypeptide comprises:

[00325] (i) an RBD, and

[00326] (ii) a stem helix and a fusion peptide of an S2 domain.

[00327] In some embodiments, a stem helix and a fusion peptide are connected via a non-endogenous peptide sequence.

[00328] In some embodiments, a stem helix and a fusion peptide are directly linked to one another and/or a stem helix and a fusion peptide are connected via a sequence that comprises a flexible linker.

[00329] In some embodiments, an RBD is connected to a stem helix and/or a fusion peptide via a non- endogenous sequence.

[00330] In some embodiments, an RBD is directly linked to the stem helix and/or the fusion peptide.

[00331] In some embodiments, an RBD is linked to a stem helix and/or a fusion peptide via a flexible linker.

[00332] In some embodiments, an RBD is N-terminal to the stem helix and the fusion peptide.

[00333] In some embodiments, an RBD is C-Terminal to the stem helix and the fusion peptide.

[00334] In some embodiments, the N-terminal to C-terminal orientation of the polypeptide is: (RBD)-(SH) -(FP), (SH)-(FP)-(RBD), (FP)-(SH)-(RBD), or (RBD)-(FP)-(SH) optionally wherein there is one or more linkers (e.g., a flexible linker) and/or domains (e.g., transmembrane domain or multimerization domains) between one or more of the RBD, stem helix, and fusion peptide.

[00335] In some embodiments, a stem helix and a fusion peptide are directly linked to one another, and wherein an RBD is N-terminal or C-terminal to the stem helix-fusion peptide region.

[00336] In some embodiments, an RNA encodes a polypetpide having an N-terminal to C-terminal orientation of:

[00337] (fusion peptide)-(stem helix)-(RBD)-(transmembrane domain); or

[00338] (RBD-(fusion peptide)-(stem helix)-(transmembrane domain).

[00339] In some embodiments, a stem helix, fusion peptide, and RBD are connected via a non-endogenous sequence

[00340] In some embodiments, a fusion peptide comprises a sequence of PSKPSKRSFIEDLLFNKVFLADAGFIKQYGDCLGD, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto, and the stem helix comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[00341] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 464 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 464; (ii) the nucleotide sequence of SEQ ID NO: 465 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 465; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 190, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 190.

[00342] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 466 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 466; (ii) the nucleotide sequence of SEQ ID NO: 467 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 467; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 191, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 191.

[00343] In some embodiments, a polypeptide comprises a secretory signal peptide (e.g., a secretory signal peptide of a viral protein), optionally wherein the secretory signal peptide is at the N-terminus of the polypeptide. [00344] In some embodiments, a secretory signal peptide is a secretory signal peptide of a SARS-CoV-2 S protein (e.g., wherein the secretory signal peptide comprises an amino acid sequence of MFVFLVLLPLVSSQCVNLT, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 variant). [00345] In some embodiments, a polypeptide comrpises one or more multimerization domains.

[00346] In some embodiments, a multimerization domain is a |3-Annulus peptide, a ferritin domain, a fibritin domain, or a lumazine synthase multimerization domain.

[00347] In some embodiments, a fJ-Annulus peptide comprises SEQ ID NO: 201, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 201.

[00348] In some embodiments, a ferritin domain comprises:

[00349] SEQ ID NO: 202, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 202; or

[00350] SEQ ID NO: 203, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 203.

[00351] In some embodiments, a fibritin domain comprises:

[00352] SEQ ID NO: 199, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 199; or

[00353] SEQ ID NO: 200, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 200.

[00354] In some embodiments, a lumazine synthase multimerization domain comprises SEQ ID NO: 204, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 204.

[00355] Among other things, the present disclosure describes an RNA comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises an antigenic fragment of an S protein, or a variant thereof, and a multimerization domain.

[00356] In some embodiments, an RNA encodes an antigenic fragment of a coronavirus S protein and a multimerization domain, where:

[00357] the antigenic fragment of the coronavirus S protein comprises an RBD and wherein the multimerization domain comprises a fJ-Annulus peptide; [00358] the antigenic fragment of the coronavirus S protein comprises an RBD and wherein the multimerization domain comprises a ferritin domain;

[00359] the antigenic fragment of the coronavirus S protein comprises an RBD and wherein the multimerization domain comprises a lumazine synthase multimerization domain;

[00360] the antigenic fragment of the coronavirus S protein comprises a truncated SI domain and wherein the multimerization domain comprises a p-Annulus peptide;

[00361] the antigenic fragment of the coronavirus S protein comprises a truncated SI domain and wherein the multimerization domain comprises a ferritin domain;

[00362] the antigenic fragment of the coronavirus S protein comprises a truncated SI domain and wherein the multimerization domain comprises a lumazine synthase multimerization domain;

[00363] the antigenic fragment of the coronavirus S protein comprises an S2 domain and wherein the multimerization domain comprises a p-Annulus peptide;

[00364] the antigenic fragment of the coronavirus S protein comprises an S2 domain and wherein the multimerization domain comprises a ferritin domain; or

[00365] the antigenic fragment of the coronavirus S protein comprises an S2 domain and wherein the multimerization domain comprises a lumazine synthase multimerization domain.

[00366] In some embodiments, an antigenic fragment of a coronavirus S protein and a multimerization domain are connected to one another via a linker.

[00367] In some embodimetns, a linker is a flexible linker, a rigid linker, or a helical linker.

[00368] In some embodiments, a linker is a flexible linker and comprises a GS linker (e.g., wherein the GS linker 5, 10, 15, or 20 amino acids in length), optioanlly wherein the GS linker comprises a sequence of (G4S)1, (G4S)2, (G4S)3, or (G4S)4.

[00369] In some embodiments, an RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

[00370] In some embodimetns, an antigenic fragment of a SARS-CoV-2 S protein comprises an RBD and an NTD of a SARS-CoV-2 S protein.

[00371] In some embodiments, an immunogenic fragment of a SARS-CoV-2 S protein comprises a truncated SI domain.

[00372] In some embodiments, an RBD is at the C-terminus of the truncated SI domain (e.g., wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant).

[00373] In some embodiments, a truncated SI domain comprises amino acids 14-528 of SEQ ID NO: 1, amino acids 17-528 of SEQ ID NO: 20-528 of SEQ ID NO: 1, amino acids 14-541 of SEQ ID NO: 1, amino acids 17-541 of SEQ ID NO: 1, or amino acids 20-541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing from an S protein of a SARS-CoV-2 variant.

[00374] In some embodiments, an RNA encodes a polypeptide comprising SEQ ID NO: 205, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 205. [00375] In some embodiments, an RNA encodes a polypeptide comprising SEQ ID NO: 206, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 206.

[00376] In some embodiments, an RNA encodes a polypeptide comprising SEQ ID NO: 207, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 207.

[00377] In some embodiments, an RNA encodes a polypeptide comprising SEQ ID NO: 208, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 208.

[00378] In some embodiments, an RNA encodes a polypeptide comprising SEQ ID NO: 209, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 209.

[00379] In some embodiments, an RNA encodes a polypeptide comprising SEQ ID NO: 210, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 210.

[00380] In some embodiments, an RNA comprises a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 211, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 211;

[00381] In some embodiments, an RNA comprises a nucleotide sequence of SEQ ID NO: 212, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 212

[00382] In some embodiments, an RNA comprises a nucleotide sequence of SEQ ID NO: 212, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 214.

[00383] Among other things, the present disclosure describes, an RNA comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises an immunogenic fragment of a SARS-CoV-2 S protein, and one or more domains that can induce formation of a viral-like particle (VLP) when the RNA is transfected into a cell.

[00384] In some embodiments, one or more domains that can induce formation of a VLP comprise an endosomal sorting complex required for transport (ESCRT)- and ALG-2-interacting protein X (ALIX) binding region (collectively referred to as EABR).

[00385] In some embodiments, an EABR sequence comprises an amino acid sequence of FNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLLAKIFELEKKTETAAHSLP, or sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to FNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLLAKIFELEKKTETAAHSLP.

[00386] In some embodiments, an EABR sequence comprises an amino acid sequence of LQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to LQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ.

[00387] In some embodiments, a polypeptide comprising an EABR sequence further comprises a transmembrane domain. [00388] In some embodiments, a transmembrane domain is a heterologous transmembrane domain or a homologous transmembrane domain.

[00389] In some embodiments, a transmembrane domain is or comprises a SARS-CoV-2 S protein transmembrane domain.

[00390] In some embodimetns, a transmembrane domain comprises an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC.

[00391] In some embodiments, an EABR and a transmembrane domain are C-terminal to a SARS-CoV-2 S protein fragment.

[00392] In some embodimetns, an EABR sequence is C-terminal to a transmembrane domain.

[00393] In some embodiments, a transmembrane domain and a EABR sequence are directly linked to one another, or a transmembrane domain and a EABR sequence are connected via a flexible linker. In some embodiments, the flexible linker connecting a transmembrane domain and an EABR sequence is a GS linker comprising about 5, about 10, about 15, or about 20 amino acids.

[00394] In some embodiments, a polypeptide comprises a peptide having an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSFNSSINNIHEMEIQLKDALEKNQQWLVYDQ QREVYVKGLLAKIFELEKKTETAAHSLP (SEQ ID NO: 441), or sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto,

[00395] optionally wherein the peptide having an amino acid sequence of SEQ ID NO: 441 or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto is at the C-terminus of the polypeptide.

[00396] In some embodiments, a polypeptide comprising an EABR further comprises an EPM sequence.

[00397] In some embodiments, an EPM sequence comprises ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY, or sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical to ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY.

[00398] In some embodiments, one or more domains that can induce formation of a VLP comprise a VSV-G transmembrane domain.

[00399] In some embodiments, a VSV-G transmembrane domain comprises an amino acid sequence of KLKHTKKRQIYTDIEMNRLGK, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to KLKHTKKRQIYTDIEMNRLGK.

[00400] In some embodiments, a VSV-G transmembrane domain comprises a sequence that is endogenously proximal to the membrane in the VSV-G protein.

[00401] In some embodiments, a sequence that is endogenously proximal to the membrane in the VSV-G protein comprises:

[00402] an amino acid sequence of IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI;

[00403] an amino acid sequence of FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI; [00404] an amino acid sequence of QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI; or [00405] an amino acid sequence of FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIor an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI.

[00406] In some embodiments, a VSV-G membrane proximal region comprises:

[00407] an amino acid sequence of

IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK;

[00408] an amino acid sequence of

FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK;

[00409] an amino acid sequence of

QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK; or [00410] an amino acid sequence of FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNR LGKor an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNR LG.

[00411] In some embodiments, a VSV-G transmembrane domain is at the C-terminus of a polypeptide.

[00412] In some embodiments, an immunogenic fragment of an S protein and a VSV-G transmembrane domain are directly linked to one another or are linked via a linker sequence.

[00413] In some embodiments, a linker sequence is a GS linker sequence, and optionally comprises about 5- 20 amino acids.

[00414] In some embodiments, a GS linker sequence comprises about 5 to about 10 amino acids.

[00415] In some embodiments, an immunogenic fragment of a SARS-CoV-2 S protein comprises an RBD, a truncated SI subdomain, and/or an S2 domain, optionally wherein the S2 domain comprises one or more mutations that increase stability.

[00416] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide that the comprises an amino acid sequence of SEQ ID NO: 411, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 411;

[00417] the RNA comprises a nucleotide sequence of SEQ ID NO: 412, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 412; and/or [00418] the RNA comprises a nucleotide sequence of SEQ ID NO: 414, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 414.

[00419] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide, wherein: [00420] the polyepptide comprises an amino acid sequence of SEQ ID NO: 406, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 406;

[00421] the RNA comprises a nucleotide sequence of SEQ ID NO: 407, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 407; and/or [00422] the RNA comprises a nucleotide sequence of SEQ ID NO: 409, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 409.

[00423] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide, wherein: [00424] the polyepptide comprises an amino acid sequence of SEQ ID NO: 416, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 416;

[00425] the RNA comprises a nucleotide sequence of SEQ ID NO: 417, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 417; and/or [00426] the RNA comprises a nucleotide sequence of SEQ ID NO: 419, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 419.

[00427] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide, wherein:

[00428] the polyepptide comprises an amino acid sequence of SEQ ID NO: 421, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 421;

[00429] the RNA comprises a nucleotide sequence of SEQ ID NO: 422, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 422; and/or [00430] the RNA comprises a nucleotide sequence of SEQ ID NO: 424, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 424.

[00431] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide, wherein: [00432] the polypeptide comprises an amino acid sequence of SEQ ID NO: 426, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 426;

[00433] the RNA comprises a nucleotide sequence of SEQ ID NO: 427, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 427; and/or [00434] the RNA comprises a nucleotide sequence of SEQ ID NO: 428, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 428.

[00435] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide, wherein:

[00436] the polyepptide comprises an amino acid sequence of SEQ ID NO: 431, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 431;

[00437] the RNA comprises a nucleotide sequence of SEQ ID NO: 432, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 432; and/or [00438] the RNA comprises a nucleotide sequence of SEQ ID NO: 434, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 434.

[00439] In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide, wherein: [00440] the polyepptide comprises an amino acid sequence of SEQ ID NO: 436, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 436;

[00441] the RNA comprises a nucleotide sequence of SEQ ID NO: 437, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 437; and/or [00442] the RNA comprises a nucleotide sequence of SEQ ID NO: 438, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 438.

[00443] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 475 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 475; (ii) the nucleotide sequence of SEQ ID NO: 176 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 476; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 474, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 474.

[00444] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 480 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 480; (ii) the nucleotide sequence of SEQ ID NO: 482 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 482; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 479, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 479.

[00445] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 484 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 484; (ii) the nucleotide sequence of SEQ ID NO: 486 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 486; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 483, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 483.

[00446] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 489 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 489; (ii) the nucleotide sequence of SEQ ID NO: 491 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 491; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 488, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 488.

[00447] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 494 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 494; (ii) the nucleotide sequence of SEQ ID NO: 496 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 496; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 493, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 493.

[00448] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 499 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 499; (ii) the nucleotide sequence of SEQ ID NO: 501 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 501; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 498, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 498.

[00449] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 504 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 504; (ii) the nucleotide sequence of SEQ ID NO: 506 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 506; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 503, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 503.

[00450] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 509 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 509; (ii) the nucleotide sequence of SEQ ID NO: 511 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 511; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 508, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 508.

[00451] In some embodiments, an RNA comprises (i) the nucleotide sequence of SEQ ID NO: 514 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 514; (ii) the nucleotide sequence of SEQ ID NO: 516 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 516; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 513, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 513.

[00452] In some embodiments, one or more domains that can induce formation of a VLP comprise a VP40 TSG101 peptide and/or a p6 Alix peptide.

[00453] In some embodiemnts, a VP40 TSG101 peptide comprises an amino acid sequence of VILPTAPPEYMEA, or an amino acid sequence having 1, 2, 3, 4, or 5 modifications relative to VILPTAPPEYMEA. [00454] In some embodiments, a p6 Alix peptide comprises:

[00455] an amino acid sequence of DKELYPLTSLRSLFGN, or an amino acid sequence having 1, 2, 3, 4, or 5 modifications relative to DKELYPLTSLRSLFGN; or

[00456] an amino acid sequence of TQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE, or an amino acid sequence having 1, 2, 3, 4, or 5 modifications relative to TQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE.

[00457] In some embodiments, a p6 Alix peptide and the VP40 TSG101 peptide are directly linked to one anotheer, or wherein the p6 Alix peptide and the VP40 TSG101 peptide are connected via a linker. In some embodiments, the linker is a flexible linker, and optionally comprises a GS linker (e.g., wherein the GS linker is about 5 to about 20 amino acids in length, including, e.g., about 5, about 10, about 15, or 20 amino acids in length).

[00458] In some embodiments, a polypeptide comprises an amino acid sequence of VILPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN, or or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to VILPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN. [00459] In some embodiments, one or more domains that can induce formation of a VLP comprise an amino acid sequence of PTAPPEYGSGSGSLYPLTSLRSLGSGSGSPTAPGSGSGSLYPDLNLDSLGSGSGSPSAP, or or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to PTAPPEYGSGSGSLYPLTSLRSLGSGSGSPTAPGSGSGSLYPDLNLDSLGSGSGSPSAP.

[00460] In some embodiments, one or more domains that can induce formation of a VLP comprise an amino acid seuqence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGS VILPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

[00461] In some embodiments, one or more domains that can induce formation of a VLP comprise an amino acid seuqence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSVILPTAPPEYMEAGSGSGSTQNLYPDLSEIK KEYNVKEKDQVEDLNLDSLWE or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

[00462] In some embodiments, one or more domains that can induce formation of a VLP comprise an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSPTAPPEYGSGSGSLYPLTSLRSLGSGSGSPT APGSGSGSLYPDLNLDSLGSGSGSPSAP or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

[00463] In some embodiments, a VP40 TSG101 peptide and/or p6 Alix peptide are C-terminal to a transmembrane domain.

[00464] In some embodiments, a transmembrane doamin and a VP40 TSG101 peptide and/or a p6 Alix peptide are C-terminal to an immunogenic fragment of a SARS-CoV-2 S protein.

[00465] In some embodiments, a VP40 TSG101 peptide and/or p6 Alix peptide are at the C-terminus of a polypeptide.

[00466] In some embodiments, an immunogenic fragment of a SARS-CoV-2 S protein comprises an RBD, a truncated SI subdomain, and/or an S2 domain, optionally wherein the S2 domain comprises one or more mutations that increase stability.

[00467] In some embodiments, an RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

[00468] In some embodiments, an immunogenic fragment of a SARS-CoV-2 S protein comprises an N- Terminal Domain (NTD).

[00469] In some embodiments, an NTD comprises amino acids 14-209, 14-303, 20-318, or 20-302 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

[00470] In some embodiments, an immunogenic fragment comprises an SI domain of a SARS-CoV-2 S protein, or an immunogenic fragment thereof.

[00471] In some embodimetns, an immunogenic fragment of a SARS-CoV-2 S protein comprises an RBD and an NTD of a SARS-CoV-2 S protein.

[00472] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 362, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical SEQ ID NO: 362. [00473] In some embodiments, an RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 362, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical SEQ ID NO: 363.

[00474] In some embodiments, an RNA encodes a polypeptide a polypeptide comprising an amino acid sequence of SEQ ID NO: 364, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical SEQ ID NO: 364.

[00475]

[00476] In some embodiments, one or more domains that can induce formation of a VLP comprise a portion of a capsid protein of Porcine circovirus 2 (PCV-2).

[00477] In some embodiments, a portion of a capsid protein of Porcine circovirus 2 (PCV-2): comprises an amino acid sequence of

MTYPRRRYRRRRHRPRSHLGQILRRRPWLVHPRHRYRWRRKNGIFNTRLSRTFGYTVKATTVRTPSWAVDMMRFNIDDFVPP GGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVNYSSRHTIPQPFSYHSRYFTPKPVLD STIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPLKP, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to MTYPRRRYRRRRHRPRSHLGQILRRRPWLVHPRHRYRWRRKNGIFNTRLSRTFGYTVKATTVRTPSWAVDMMRFNIDDFVPP GGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVNYSSRHTIPQPFSYHSRYFTPKPVLD STIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPLKP; and/or is encoded by a nucleotide sequence of

AUGACGUAUCCAAGGAGGCGUUACCGCAGAAGAAGACACCGCCCCCGCAGCCAUCUUGGCCAGAUCCUCCGCCGCCGCCC CUGGCUCGUCCACCCCCGCCACCGCUACCGUUGGAGAAGGAAAAAUGGCAUCUUCAACACCCGCCUCUCCCGCACCUUCG GAUAUACUGUCAAGGCUACCACAGUCAGAACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUGU UCCCCCGGGAGGGGGGACCAACAAAAUCUCUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGGC CCUGCUCCCCCAUCACCCAGGGUGAUAGGGGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGGC CACAGCCCUAACCUAUGACCCAUAUGUAAACUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUUA CUUCACACCCAAACCUGUUCUUGACUCCACUAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGGC UACAAACCUCUAGAAAUGUGGACCACGUAGGCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAUC CGUGUAACCAUGUAUGUACAAUUCAGAGAAUUUAAUCUUAAAGACCCCCCACUUAAACCC, or a nucleotide sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical toAUGACGUAUCCAAGGAGGCGUUACCGCAGAAGAAGACACCGCCCCCGCAGCCAUCUUGGCCAGAUCCUCCGCCGCCGCC CCUGGCUCGUCCACCCCCGCCACCGCUACCGUUGGAGAAGGAAAAAUGGCAUCUUCAACACCCGCCUCUCCCGCACCUUC GGAUAUACUGUCAAGGCUACCACAGUCAGAACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUG UUCCCCCGGGAGGGGGGACCAACAAAAUCUCUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGG CCCUGCUCCCCCAUCACCCAGGGUGAUAGGGGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGG CCACAGCCCUAACCUAUGACCCAUAUGUAAACUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUU ACUUCACACCCAAACCUGUUCUUGACUCCACUAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGG CUACAAACCUCUAGAAAUGUGGACCACGUAGGCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAU CCGUGUAACCAUGUAUGUACAAUUCAGAGAAUUUAAUCUUAAAGACCCCCCACUUAAACCC.

[00478] In some embodiments, a portion of a capsid protein of PCV-2: comprises an amino acid sequence of

TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSFAVILDDNFVTKATALTYDPYVNYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPP, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVNYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPP; and/or is encoded by a nucleotide sequence of ACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUGUUCCCCCGGGAGGGGGGACCAACAAAAUCU CUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGGCCCUGCUCCCCCAUCACCCAGGGUGAUAGG GGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGGCCACAGCCCUAACCUAUGACCCAUAUGUAAA CUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUUACUUCACACCCAAACCUGUUCUUGACUCCAC UAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGGCUACAAACCUCUAGAAAUGUGGACCACGUAG GCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAUCCGUGUAACCAUGUAUGUACAAUUCAGAGAA UUUAAUCUUAAAGACCCCCCACUU, or a nucleotide sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical ACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUGUUCCCCCGGGAGGGGGGACCAACAAAAUCU CUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGGCCCUGCUCCCCCAUCACCCAGGGUGAUAGG GGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGGCCACAGCCCUAACCUAUGACCCAUAUGUAAA CUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUUACUUCACACCCAAACCUGUUCUUGACUCCAC UAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGGCUACAAACCUCUAGAAAUGUGGACCACGUAG GCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAUCCGUGUAACCAUGUAUGUACAAUUCAGAGAA UUUAAUCUUAAAGACCCCCCACUU.

[00479] In some embodiments, a portion of a capsid protein of PCV-2 comprises an amino acid sequence of TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVDYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPL, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVDYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPL. [00480] In some embodiments, a portion of a PCV-2 capside protein is at the C-terminus of a polypeptide.

[00481] In some embodiments, a polypeptide comprises a secretory signal peptide that comprises (i) an amino acid sequence that is listed in Table 2 or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to an amino acid sequence that is listed in Table 2, and/or (ii) wherein the RNA comprises a nucleotide sequence that is listed in Table 3 or a nucleotide sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to an amino acid sequence that is listed in Table 2.

[00482] In some embodiments, a polypeptide comprises an SP24-Q7PUJ5_ANOGA secretory signal peptide (e.g., a secretory signal peptide comprising an amino acid sequence of MCRGLSAVLILLVSLSAQLHVWG (SEQ ID NO: 22) or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MCRGLSAVLILLVSLSAQLHVWG (SEQ ID NO: 22)).

[00483] In some embodiments, a polypeptide comprises an SP24-SP18-HEMA_CVBM secretory signal peptide (e.g., a secretory signal peptide comprising the amino acid sequence of MFLLLRFVLVSCIIGSLG (SEQ ID NO: 391) or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MFLLLRFVLVSCIIGSLG (SEQ ID NO: 391).

[00484] In some embodiments, a polypeptide comprises an SP25-GD_HHV1K secretory signal peptide (e.g., a secretory signal peptide comprising an amino acid sequence of MGGAAARLGAVILFWIVGLHGVRG (SEQ ID NO: 12) or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MGGAAARLGAVILFWIVGLHGVRG (SEQ ID NO: 12).

[00485] In some embodiments, a polypeptide comprises an SP32-GB_HHV1K secretory signal peptide (e.g., a secretory signal peptide comprising the amino acid sequence of MHQGAPSWGRRWFWWALLGLTLGVLVASAAP (SEQ ID NO: 38) or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MHQGAPSWGRRWFWWALLGLTLGVLVASAAP (SEQ ID NO: 38).

[00486] In some embodiments, a polypeptide comprises an SP20-A7U881_HHV2 secretory signal peptide (e.g., a secretory signal peptide comprising the amino acid sequence of MARGAGLVFFVGVWWSCLA (SEQ ID NO: 366) or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MARGAGLVFFVGVWWSCLA (SEQ ID NO: 366).

[00487] In some embodiments, an RNA comprises a 5' cap, a cap proximal sequence, a 5' UTR sequence, a 3' UTR sequence, and a polyA sequence.

[00488] In some embodiments,

(i) a 5' cap comprises a Capl structure;

(ii) a 5'-UTR sequence comprises a modified human alpha-globin 5'-UTR;

(iii) a 3'-UTR sequence comprises a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA;

(iv) a polyA sequence comprises at least 100 A nucleotides; or

(v) a combination of any one of (i)-(iv).

[00489] In some embodiments, a 5' cap comprises a Capl structure, and the Capl structure comprises m7(3'OMeG)(5')ppp(5')(2'OMeAl)pG2, wherein Al is position +1 of the RNA, and G2 is position +2 of the RNA. [00490] In some embodiments, a cap proximal sequence comprises Al and G2 of the Capl structure, and a sequence comprising: A3N4N5 at positions +3, +4 and +5 respectively of the RNA, wherein N4 and N5 are each independently selected from A, G, C, and U.

[00491] In some embodiments, a polyA sequence comprises an interrupted sequence of A nucleotides, optionally wherein the interrupted sequence comprises 30 adenine nucleotides followed by 70 adenine nucleotides, wherein the 30 adenine nucleotides and 70 adenine nucleotides are separated by a linker sequence. [00492] In some embodiments, a 5'-UTR sequence comprises SEQ ID NO: 12, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 12. [00493] In some embodiments, a 3'-UTR sequence comprises SEQ ID NO: 13, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 13. In some embodiments, a 3'-UTR sequence comprises SEQ ID NO: 601, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 601. In some embodiments, a 3'-UTR sequence comprises SEQ ID NO: 602, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 602.

[00494] In some embodiments, an interrupted polyA tail sequence comprises SEQ ID NO: 14, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 14. [00495] In some embodiments, a sequence at the 5' end of the 3'UTR sequence (e.g., the sequence immediately adjacent to a sequence encoding an antigenic polypeptide) is CUCGAG or GGAUCCGAU.

[00496] In some embodiments, an RNA is saRNA, self-amplifying RNA, trans-amplifying RNA (taRNA), or mRNA.

[00497] In some embodiments, an RNA is unmodified RNA or wherein the RNA comprises one or modified uridines in place of one or more uridines.

[00498] In some embodiments, an RNA comprises a single modified uridine in place of each uridine.

[00499] In some embodiments, a modified uridine is Nl-methyl-pseudouridine.

[00500] In some embodiments, a nucleotide sequence encoding the SARS-CoV-2 S protein is encoded by a sequence that is codon-optimized (e.g., codon-optimized for expression in human cells) and/or which has a G/C content that is increased compared to a wild type coding sequence.

[00501] In some embodiments, an RNA is formulated in a nanoparticle.

[00502] In some embodiments, a nanoparticle is a lipid nanoparticle, a polyplex (PLX), a lipidated polyplex (LPLX), a liposome, or a polysaccharide nanoparticle.

[00503] In some embodiments, a nanoparticle is a lipid nanoparticle.

[00504] In some embodiments, a lipid nanoparticle comprises a cationically ionizable lipid, a sterol, a neutral lipid, and a polymer-conjugated lipid.

[00505] In some embodiments, a polymer-conjugated lipid comprises a PEG-conjugated lipid.

[00506] In some embodiments, an RNA is encapsulated in a lipid nanoparticle (LNP), preferably wherein the LNP comprises molar ratios of 20-60% ionizable cationic lipid, 5-25% neutral lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid.

[00507] In some embodiments, nanoparticles have an average diameter of about 50-150 nm.

[00508] In some embodiments, a composition comprises a cryoprotectant, optionally wherein the cryoprotectant is or comprises sucrose.

[00509] In some embodiments, a composition comprises an aqueous buffered solution, optionally wherein the aqueous buffered solution comprises one or more of Tris base, Tris HCI, NaCI, KCI, Na2HPO4, and KH2PO4. [00510] In some embodiments, a compostion comprises about 10 mM Tris buffer and about 10% sucrose.

[00511] Among other things, the present disclosure describes a pharmaceutical composition comprising (i) an RNA or composition described herein and (ii) a pharmaceutically acceptable excipient.

[00512] In some embodiments, a pharmaceutical composition is formulated as a multi-dose formulation in a vial, a single-dose formulation in a vial, or a prefilled syringe.

[00513] In some embodiments, a pharmaceutical composition is formulated to provide a dose of about 100 μg or less (e.g., about 90 μg or less) of total RNA.

[00514] In some embodiments, a pharmaceutical composition is formulated to provide a dose of about 90 pg, about 60 pg, about 30 pg, about 25 pg, about 20 pg, about 10 pg, about 6 pg, about 5 pg, or about 3 μg of total RNA.

[00515] Among other things, the present disclosure describes a method comprising administering an RNA, composition, or pharmaceutical composition described herein to a subject.

[00516] In some embodiments, if a subject is 12 years or older, a method comprises administering 30 μg of the RNA. In some embodiments, if a subject is 5 years to less than 12 years old, a method comprises administering 10 μg of the RNA. In some embodiments, if a subject is 6 months to less than 5 years old, a method comprises administering 3 μg of the RNA. In some embodiments, a composition described herein is administered in a volume of about 200 pL to about 300 μL.

[00517] In some embodiments, a subject has not previously been administered a SARS-CoV-2 vaccine and/or wherein the subject has not previously been determined to have been infected with SARS-CoV-2 (e.g., as determined using a PCR or antigen test).

[00518] In some embodiments, a method comprises administering a single dose of RNA, composition, or pharmaceutical composition to a subject.

[00519] In some embodiments, a method comprises administering two or more doses of the RNA, composition, or pharmaceutical composition to a subject, optionally wherein the two doses are administered about 21 days apart.

[00520] In some embodiments, RNA, composition, or pharmaceutical composition is administered three times to a subject, optionally wherein a first and a second dose are administered about 21 days apart, and a third dose is administered about 28 days after the second dose.

[00521] In some embodiments, a method comprises administering a further dose of the RNA, composition, or pharmaceutical composition, at least about 2 months after the first dose of the RNA, composition, or pharmaceutical composition (e.g., 2-12 months, 2-10 months, 2-8 months, about 2 months, about 3 months, about 4 months, about 5 months, or about 6 months).

[00522] In some embodiments, a subject has previously been exposed to a SARS-CoV-2 antigen (e.g., by vaccination and/or by infection).

[00523] In some embodiments, a subject was previously administered one or more doses of a SARS-CoV-2 vaccine.

[00524] In some embodimetns, a subject was previously administered a complete dosing regimen of a SARS-CoV-2 vaccine.

[00525] In some embodiments, a subject was previously administered a first dose and a second dose of a vaccine that delivers a full length SARS-CoV-2 S protein (e.g., a composition comprising LNP-formulated RNA encoding a SARS-CoV-2 S protein), wherein the first dose and the second dose were administered about 21 days apart, and optionally wherein the subject was previously administered as a booster dose a monovalent or bivalent vaccine that delivers a SARS-CoV-2 S protein of one or more variants (e.g., (i) an S protein of a Wuhan strain and an S protein of an Omicron BA.4/5 strain, (ii) an S protein of an XBB.1.5 variant, (iii) an S protein of a KP.2 variant, and/or (iv) an S protein of a JN.l variant).

[00526] In some embodiments, a method comprises administering one or more vaccines against a non- SARS-CoV-2 disease, optionally wherein the one or more vaccines comprises an RSV vaccine, an influenza vaccine, or a combination thereof.

[00527] In some embodiments, method described herein can induce an immune response against SARS- CoV-2 in the subject.

[00528] In some embodiments, an immune response comprises a B-cell response.

[00529] In some embodiments, a B cell response comprises production of antibodies directed against one or more SARS-CoV-2 viruses.

[00530] In some embodiments, an immune response comprises a T cell response, optionally wherein the T- cell response comprises a CD4+ T cell response and/or CD8+ T cell response.

[00531] In some embodiments, a method is a method of preventing or reducing the chances of being infected with a SARS-CoV-2 virus and/or treating a SARS-CoV-2 infection. [00532] In some embodiments, an RNA, composition, or pharmaceutical composition described herein can be used to induce an immune response in a subject. In some embodiments, an immune response is induced usign a method described herein.

[00533] In some embodiments, an RNA, composition, or pharmaceutical composition described herein can be used for the manufacture of a medicament for inducing an immune response in a subject. In some embodiments, a medicament is formulated to be administered to a subject in accordance with a method described herein.

[00534] Among other things, the present disclosure provides a method of manufacturign RNA, wherein the method comprises in vitro transcribing an RNA described herein.

[00535] In some embodiments, a ribonucleic acid (RNA) comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises:

(i) a receptor binding domain (RBD) of a coronavirus Spike (S) protein; and

(ii) an S2 domain of a coronavirus S protein or one or more fragments thereof; wherein the RBD and the S2 domain or the one or more fragments thereof are directly adjacent to one another or are connected via a non-endogenous sequence.

Brief description of the drawings

[00536] Fig. 1. Schematic Overview of the S Protein Organization of the SARS-CoV-2 S Protein.

The sequence within the SI subunit in the native SARS-CoV-2 S protein comprises a signal sequence (SS) and the receptor binding domain (RBD) which is a subunit within the S protein that is relevant for binding to the human cellular receptor ACE2. The S2 subunit in the native SARS-CoV-2 S protein contains the S2 protease cleavage site (529 followed by a fusion peptide (FP) for membrane fusion, heptad repeats (HR1 and HR2) with a central helix (CH) domain, the transmembrane domain (TM) and a cytoplasmic tail (CT).

[00537] Fig. 2. Schematics of an Exemplary Dosing Regimen.

[00538] Fig. 3. Sequences of RBDs of SARS-COV-2 Wuhan strain and Variants Thereof. Variantspecific amino acid alterations are indicated in bold red font, with the original Wuhan amino acid highlighted in bold blue font.

[00539] Fig. 4. Exemplary Polypeptides Comprising an S2 Polypeptide, an RBD, an NTD, and/or Fragments of an S2 Polypeptide. (A) Depects exemplary designs of polypeptides comprising a secretory signal peptide C'SP), a Receptor Binding Domain (RBD), an S2 domain, a transmembrane domain ("TM), and a C- terminal sequence. Lightening bolts are used to indicate linkers that comprise a protease cleavage site (e.g., a human furin protease) (e.g., a sequence described herein). (B) Depects Exemplary construct designs for polypeptides comprising an S2 domain, optionally with one or more mutations that stabilize a prefusion confirmation of the S2 polypeptide (indicated with in the figure) and a fibritin trimerization domain ("F"). (B) Also depicts exemplary polyepptides comprising a stem helix and fusion peptide of an S2 domain and an S2 and RBD, optionally with one or more muations that stabilize a prefusion confirmation fo the S2 domain and a prease cleavage site.

[00540] Fig. 5. Exemplary Polypeptides Comprising a SARS-Cov-2 Antigen That are Capable of Producing Viral Like Particles (VLPs). "C" stands for a capsid protein of Porcine circovirus 2. "SP" refers to a secretory signal peptide.

[00541] Fig. 6. Exemplary Polypeptide Comprising a SARS-Cov-2 Antigen and Components For Forming a VLP (EABR and EPM). [00542] Fig. 7. In Vitro Expression of Soluble S2 Polypeptides. (A) and (B) show intracellular S2 polypeptide signal in cells (% positive cells and mean flource intensity (MFI) receptively) transfected with an RNA encoding a full length S protein (Construct 1) and cells transfected with various RNAs described herein that encode a polypeptide comprising an S2 polypeptide with one or more stabilizing mutations, and which lack a transmembrane domain (Constructs 2-8). Signal was assessed using a fluorescently labeled antibody that binds the S2 polypeptide region. As shown, each of the constructs tested produced detectable S2 signal. Further information regarding the characterized constructs is provided in Example 5.

[00543] Fig. 8. In Vitro Stem Helix (SH) Signal Produced by RNA Encoding Soluble S2

Polypeptides. (A)-(C) Show intracellular Stem Helix (SH) signal measured in cells transfected with RNA encoding a full length S protein (Construct 1) and various RNAs described herein that encode a polypeptide comprising an S2 polypeptide with one or more stabilizing mutations and which lack a transmembrane domain (Constructs 2-7). SH signal was measured using three different antibodies, each of which had previously been shown to bind to the SH region and also to be capable of neutralizing a SARS-CoV-2 virus (SH nAbl-3). As shown in each of (A)-(C), RNA encoding an S2 polypeptide was shown to result in increased SH signal for each construct tested. Further information regarding the characterized constructs is provided in Example 5.

[00544] Fig. 9. In Vitro Fusion Peptide (FP) Signal Produced by RNA Encoding Soluble S2 Polypeptides. (A)-(C) Show intracellular Fusion Peptide (FP) signal observed for an RNA encoding a full length S protein (Construct 1), and various RNAs described herein that encode a polypeptide comprising an S2 polypeptide with one or more stabilizing mutations and which lack a transmembrane domain (Constructs 2-7). Cells were transfected with one of the indicated RNA molecules, and intracellular FP signal was measured using three different antibodies that had previously been shown to bind to the FP region and to be capable of neutralizing a SARS-CoV-2 virus (FP nAbl-3). As shown, low FP signal was observed for an RNA encoding a full length S protein. Certain RNA molecules described herein, in contrast, displayed strong FP signal. Further information regarding the characterized constructs is provided in Example 5.

[00545] Fig. 10. Exemplary RBD-S2 and RBD-SH-FP Constructs. Shown are exemplary designs for polypeptides encoded by RNA described herein. TM is an abbreviation for transmembrane domain.

[00546] Fig. 11. RBD Signal Produced by RNA Encoding an S2 Polypeptide or SH and FP Peptides, and Optionally Linked to an RBD. Cells were transfected with RNA encoding (1) a full length S protein (Construct 1), (2) RNA encoding an S2 polypeptide (Construct 2), (3) RNA encoding a polypeptide comprising an RBD, a transmembrane domain, and a fibritin domain, and lacking regions from the S2 polypeptide (Construct 3), (4) RNA encoding an S2 polypeptide linked to an RBD (Constructs 4-6), or (5) RNA encoding a polypeptide comprising an RBD linked to an SH and FP region of the S2 polypeptide (Constructs 7 and 8). Shown is cell surface RBD signal, as determined using a flouresently labeled ACE2 protein. As shown, certain RNA molecules described herein can result in significantly increased cell surface expression of RBD as compared to RNA encoding a full length S protein. Further information regarding the characterized constructs is provided in Example 6.

[00547] Fig. 12. In Vitro S2 Signal Produced by RNA Encoding an S2 Polypeptide or SH and FP Peptides, and Optionally Linked to an RBD. Cells were transfected with RNA encoding (1) a full length S protein (Construct 1), (2) RNA encoding an S2 polypeptide (Construct 2), (3) RNA encoding a polypeptide comprising an RBD, a transmembrane domain, and a fibritin domain, and lacking regions from the S2 polypeptide (Construct 3), (4) RNA encoding an S2 polypeptide linked to an RBD (Constructs 4-6), or (5) RNA encoding a polypeptide comprising an RBD linked to an SH and FP region of the S2 polypeptide (Constructs 7 and 8). Intracellular (shown in (A)) and cell surface (shown in (B)) S2 signal was then measured using an antibody that binds the S2 polypeptide. As shown, RNA described herein induced higher intracellular S2 signal as compared to RNA encoding a full length S protein. An RNA encoding an RBD and SH and FP regions of the S protein (Construct 8) was also shown to induce higher cell surface S protein signal as compared to RNA encoding a full length S protein. Further information regarding the characterized constructs is provided in Example 6.

[00548] Fig. 13. In Vitro Stem Helix (SH) Signal Produced by RNA Encoding an S2 Polypeptide or SH and FP Peptides, and Optionally Linked to an RBD. Cells were transfected with RNA encoding (1) a full length S protein (Construct 1), (2) RNA encoding an S2 polypeptide (Construct 2), (3) RNA encoding a polypeptide comprising an RBD, a transmembrane domain, and a fibritin domain, and lacking regions from the S2 polypeptide (Construct 3), (4) RNA encoding an S2 polypeptide linked to an RBD (Constructs 4-6), or (5) RNA encoding a polypeptide comprising an RBD linked to an SH and FP region of the S2 polypeptide (Constructs 7 and 8). Intracellular (shown in (A)) and cell surface (shown in (B)) SH signal was then measured using an antibody previously shown to bind the SH region and to be capable of neutralizing a SARS-CoV-2 virus. As shown, RNA encoding an S2 polypeptide or an SH and FP peptide was shown to result in increased intracellular SH signal for each construct tested. Constructs comprising an SH and FP region linked to an RBD (Constructs 7 and 8) were also shown to produce higher cell surface SH signal as compared to RNA encoding a full length S protein. Further information regarding the characterized constructs is provided in Example 6.

[00549] Fig. 14. In Vitro Fusion Peptide (FP) Signal Produced by RNA Encoding an S2 Polypeptide or SH and FP Peptides, and Optionally Linked to an RBD. Cells were transfected with RNA encoding (1) a full length S protein (Construct 1), (2) RNA encoding an S2 polypeptide (Construct 2), (3) RNA encoding a polypeptide comprising an RBD, a transmembrane domain, and a fibritin domain, and lacking regions from the S2 polypeptide (Construct 3), (4) RNA encoding an S2 polypeptide linked to an RBD (Constructs 4-6), or (5) RNA encoding a polypeptide comprising an RBD linked to an SH and FP region of the S2 polypeptide (Constructs 7 and 8). Intracellular (shown in (A)) and cell surface (shown in (B) FP signal was then measured using an antibody previously shown to bind the FP region and to be capable of neutralizing a SARS-CoV-2 virus.

As shown, RNA encoding an S2 polypeptide or an SH and FP peptide was shown to result in increased intracellular FP signal for each construct tested while low FP signal was observed for Construct 1 (encoding a full length S protein). Constructs encoding a polypeptide comprising an SH, FP, and RBD regions of a SARS-CoV-2 S protein were also shown to produce much higher cell surface FP signal. Further information regarding the characterized constructs is provided in Example 6.

[00550] Fig. 15. Exemplary Experimental Protocol for Characterizing Immune Responses in

Vaccine Naive Mice. Two doses of the indicated composition were administered about 21 days apart. Serum samples were collected before administering a composition and 7, 14, 21, and 34 days after administering the first dose. On day 34, final samples were collected and mice were sacrificed.

[00551] Fig. 16. Neutralization Titers Induced in Vaccine Naive Mice by RNA Encoding an S2 Polypeptide and an RBD or SH and FP Peptides and an RBD. (A)-(D) Show neutralization titers against XBB.1.5-adapted, BA.4/5-adapted, and Wuhan-adapted pseudoviruses measured in sera samples collected from mice administered compositions in accordance with the protocol indicated in Fig. 15. Neutralization titers 7, 14, 21, and 34 days after administering the indicated composition are shown. As demonstrated in (D), by day 34, neutralization titers induced by Construct 5 (encoding a polypeptide comprising comprising an RBD, SH, and FP of a SARS-CoV-2 S protein) were ~1.5x those induced by Construct 1 (encoding a full length S protein) for both an XBB.1.5 and BA.4/5-adapted pseudovirus. Neutralizing titers induced by Construct 3 (encoding a polypeptide comprising an S2 and RBD) against a Wuhan S protein, were ~2x those induced by Construct 1, demonstrating increased cross-neutralization. "XBB.1.5" refers to neutralizing titers measured in a repetition of the pVNT assay against XBB.l.S-adpated pseudoviruses.

[00552] Fig. 17. Antibody Titers Induced in Vaccine Naive Mice by RNAs Encoding an S2 Polypeptide and an RBD or SH and FP Peptides and an RBD (ELISA Data). (A) and (B) Show antibody titers as determined using ELISA against an XBB.1.5 RBD and a Wuhan RBD, respectively, in sera samples collected at day 34 of the experiment summarized in Fig. 15. As shown, Constructs 4 and 5 (encoding an RBD linked to an SH and an FP) resulted in significantly increased antibody titers as compared to Construct 1 (encoding a full length S protein).

[00553] Fig. 18. Assessing VLP Formation and (3-Annulus Tagged Polypeptide Expression. (A) Provides a schematic summarizing the design of certain constructs described herein. "L" refers to a linker. (B) Provides the membrane proximal sequence of a VSV-G protein, and indicates the different membrane proximal sequences described therein. (C) Provides supernatant RBD signal from cells transfected with RNA encoding a SARS-CoV-2 antigen (RBD or a truncated SI domain) and a transmembrane domain (VSV-GJong, VSV-G_short, or SARS-CoV-2 transmembrane domain) or a p-Annulus multimerization domain. As expected, 4012, the one RNA encoding a polypeptide lacking a transmembrane domain, exhibited the highest supernatant signal. Each of the RNAs encoding a polypeptide comprising a VSV-G transmembrane domain also produced supernatant signal, which is consistent with VLP formation, as any VLPs formed would be expected to remain in the supernatant. VSV-GJong, in particular, may be especially effective at promoting VLP formation, given the high supernatant signal it produced.

[00554] Fig. 19. Assessing Immunogenicity of VLP Inducing RNA. (A)-(F) GMTs (geometric mean titers) against an XBB.1.5-adapted pseudovirus in serum samples collected from mice administered two doses (21 days apart) of the indicated composition.

[00555] Fig. 20. Characterizing VLP Formation In Vitro Using Polypeptides Comprising a VSV-G transmembrane domain and an RBD. RNA encoding polypeptides comprising an RBD and different VSV-G domains were transfected into cells. (A) Shows RBD signal as assessed in the supernatant and at the cell surface. (B) Shows RBD concentration measured in the supernatant of cells transfected with a certain amount of RNA. Each of the VSV-G transmembrane domains was found to produce increased supernatant signal and decreased cell surface signal as compared to an RNA encoding a SARS-CoV-2 antigen linked to a SARS-CoV-2 transmembrane domain, which is consistent with these transmembrane domains being capable of inducing VLP formation. VSV-GJong and VSV-G_mid_Q427 may be especially effective at inducing VLP formation, given the high supernatant signal and low cell surface signal produced by these constructs.

[00556] Fig. 21. Characterizing VLP Formation In Vitro Using Polypeptides Comprising a VSV-G transmembrane domain and a truncated SI Domain. RNA encoding polypeptides comprising a truncated SI domain and different VSV-G domains were transfected into cells. (A) Shows RBD signal as assessed in the supernatant and at the cell surface. (B) Shows RBD concentration measured in the supernatant of cells transfected with a certain amount of RNA. Each of the VSV-G transmembrane domains was found to produce increased supernatant signal and decreased cell surface signal as compared to an RNA encoding a SARS-CoV-2 antigen linked to a SARS-CoV-2 transmembrane domain, which is consistent with these transmembrane domains being capable of inducing VLP formation. VSV-GJong and VSV-G_mid_Q427 may be especially effective at inducing VLP formation, given the high supernatant signal and low cell surface signal produced by these constructs. [00557] Fig. 22. Assessing Immunogenicity of VLP Inducing RNA. (A)-(F) GMTs (geometric mean titers) against an XBB.l.S-adapted pseudovirus in serum samples collected from mice administered a single dose of the indicated composition.

[00558] Fig. 23. Improved GS Linkers for VSV-G and (3-Annulus Polypeptides. (A) and (B) show cell surface (membrane-exposed) and supernatant (soluble antigen) RBD signal observed in cells transfected with various RNAs encoding a polypeptide comprising a truncated SI polypeptide and a VSV-G_mid_Q427 transmembrane domain, which are identical except for the linker sequence connecting the truncated SI domain and the transmembrane domain. As shown, a GS linker comprising 5 or 10 amino acids resulted in increased cell surface and supernatant expression as compared to a GS linker comprising 15 amino acids. (C) Characterizes the RBD signal (soluble antigen) observed in the supernatant of cell cultures transfected with RNAs encoding a polypeptide comprising a truncated SI domain and a fJ-Annulus multimerization domain, and which are identical other than the linker connecting the p-Annulus multimerization domain and the truncated SI domain. As shown, a 5 amino acid long GS linker resulted in increased soluble antigen expression as compared to a GS linker comprising 10, 15, or 20 amino acids.

Detailed description

[00559] Although the present disclosure is described in detail below, it is to be understood that this disclosure is not limited to the particular methodologies, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present disclosure which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[00560] Preferably, the terms used herein are defined as described in "A multilingual glossary of biotechnological terms: (IUPAC Recommendations)", H.G.W. Leuenberger, B. Nagel, and H. Kolbl, Eds., Helvetica Chimica Acta, CH-4010 Basel, Switzerland, (1995).

[00561] The practice of the present disclosure will employ, unless otherwise indicated, conventional methods of chemistry, biochemistry, cell biology, immunology, and recombinant DNA techniques which are explained in the literature in the field (cf., e.g., Molecular Cloning: A Laboratory Manual, 2nd Edition, J. Sambrook et al. eds., Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1989).

[00562] In the following, the elements of the present disclosure will be described. These elements are listed with specific embodiments, however, it should be understood that they may be combined in any manner and in any number to create additional embodiments. The variously described examples and embodiments should not be construed to limit the present disclosure to only the explicitly described embodiments. This description should be understood to disclose and encompass embodiments which combine the explicitly described embodiments with any number of the disclosed elements. Furthermore, any permutations and combinations of all described elements should be considered disclosed by this description unless the context indicates otherwise.

[00563] Several documents are cited throughout the text of this specification. Each of the documents cited herein (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.), whether supra or infra, are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the present disclosure was not entitled to antedate such disclosure.

Definitions [00564] In the following, definitions will be provided which apply to all aspects of the present disclosure. The following terms have the following meanings unless otherwise indicated. Any undefined terms have their art recognized meanings.

[00565] The term "about" means approximately or nearly, and in the context of a numerical value or range set forth herein in one embodiment means ± 20%, ± 10%, ± 5%, or ± 3% of the numerical value or range recited or claimed.

[00566] The terms "a" and "an" and "the" and similar reference used in the context of describing the present disclosure (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it was individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as"), provided herein is intended merely to better illustrate the disclosure and does not pose a limitation on the scope of the claims. No language in the specification should be construed as indicating any non-daimed element essential to the practice of the disclosure.

[00567] "Activation" or "stimulation", as used herein, refers to the state of an immune effector cell such as T cell that has been sufficiently stimulated to induce detectable cellular proliferation. Activation can also be associated with initiation of signaling pathways, induced cytokine production, and detectable effector functions. The term "activated immune effector cells" refers to, among other things, immune effector cells that are undergoing cell division.

[00568] The term "antigen" relates to an agent comprising an epitope against which an immune response can be generated. The term "antigen" includes, in particular, proteins and peptides. In one embodiment, an antigen is presented by cells of the immune system such as antigen presenting cells like dendritic cells or macrophages. An antigen or a procession product thereof such as a T-cell epitope is in one embodiment bound by a T- or B-cell receptor, or by an immunoglobulin molecule such as an antibody. Accordingly, an antigen or a procession product thereof may react specifically with antibodies orT lymphocytes (T cells). In one embodiment, an antigen is a viral antigen, such as a coronavirus S protein, e.g., SARS-CoV-2 S protein, and an epitope is derived from such antigen.

[00569] The term "viral antigen" refers to any viral component having antigenic properties, i.e. being able to provoke an immune response in an individual. The viral antigen may be coronavirus S protein, e.g., SARS-CoV-2 S protein.

[00570] "Cell surface" or "surface of a cell" is used in accordance with its normal meaning in the art, and thus includes the outside of the cell which is accessible to binding by proteins and other molecules. An antigen is expressed on the surface of cells if it is located at the surface of said cells and is accessible to binding by e.g. antigen-specific antibodies added to the cells.

[00571] The term "expressed on the cell surface" or "associated with the cell surface" means that a molecule such as an antigen is associated with and located at the plasma membrane of a cell, wherein at least a part of the molecule faces the extracellular space of said cell and is accessible from the outside of said cell, e.g., by antibodies located outside the cell. In this context, a part is preferably at least 4, preferably at least 8, preferably at least 12, more preferably at least 20 amino acids. The association may be direct or indirect. For example, the association may be by one or more transmembrane domains, one or more lipid anchors, or by the interaction with any other protein, lipid, saccharide, or other structure that can be found on the outer leaflet of the plasma membrane of a cell. For example, a molecule associated with the surface of a cell may be a transmembrane protein having an extracellular portion or may be a protein associated with the surface of a cell by interacting with another protein that is a transmembrane protein.

[00572] The term "clonal expansion" or "expansion" refers to a process wherein a specific entity is multiplied. In the context of the present disclosure, the term is preferably used in the context of an immunological response in which immune effector cells are stimulated by an antigen, proliferate, and the specific immune effector cell recognizing said antigen is amplified. Preferably, clonal expansion leads to differentiation of the immune effector cells.

[00573] Unless expressly specified otherwise, the term "comprising" is used in the context of the present document to indicate that further members may optionally be present in addition to the members of the list introduced by "comprising". It is, however, contemplated as a specific embodiment of the present disclosure that the term "comprising" encompasses the possibility of no further members being present, i.e., for the purpose of this embodiment "comprising" is to be understood as having the meaning of "consisting of or "consisting essentially of".

[00574] The term "extracellular portion" or "exodomain" in the context of the present disclosure refers to a part of a molecule such as a protein that is facing the extracellular space of a cell and preferably is accessible from the outside of said cell, e.g., by binding molecules such as antibodies located outside the cell. Preferably, the term refers to one or more extracellular loops or domains or a fragment thereof.

[00575] The term "epitope" refers to a part or fragment of a molecule such as an antigen that is recognized by the immune system. For example, the epitope may be recognized by T cells, B cells or antibodies. An epitope of an antigen may include a continuous or discontinuous portion of the antigen and may be between about 5 and about 100, such as between about 5 and about 50, more preferably between about 8 and about 30, most preferably between about 8 and about 25 amino acids in length, for example, the epitope may be preferably 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids in length. In one embodiment, an epitope is between about 10 and about 25 amino acids in length. The term "epitope" includes T cell epitopes. [00576] "Fragment", with reference to an amino acid sequence (peptide or protein), relates to a part of an amino acid sequence, i.e. a sequence which represents the amino acid sequence shortened at the N-terminus and/or C-terminus. A fragment shortened at the C-terminus (N-terminal fragment) is obtainable e.g. by translation of a truncated open reading frame that lacks the 3'-end of the open reading frame. A fragment shortened at the N-terminus (C-terminal fragment) is obtainable e.g. by translation of a truncated open reading frame that lacks the 5'-end of the open reading frame, as long as the truncated open reading frame comprises a start codon that serves to initiate translation. A fragment of an amino acid sequence comprises e.g. at least 50 %, at least 60 %, at least 70 %, at least 80%, at least 90% of the amino acid residues from an amino acid sequence. A fragment of an amino acid sequence preferably comprises at least 6, in particular at least 8, at least 12, at least 15, at least 20, at least 30, at least 50, or at least 100 consecutive amino acids from an amino acid sequence.

[00577] The term "immunologically equivalent" means that the immunologically equivalent molecule such as the immunologically equivalent amino acid sequence exhibits the same or essentially the same immunological properties and/or exerts the same or essentially the same immunological effects, e.g., with respect to the type of the immunological effect. In the context of the present disclosure, the term "immunologically equivalent" is preferably used with respect to the immunological effects or properties of antigens or antigen variants used for immunization. For example, an amino acid sequence is immunologically equivalent to a reference amino acid sequence if said amino acid sequence when exposed to the immune system of a subject induces an immune reaction having a specificity of reacting with the reference amino acid sequence.

[00578] Terms such as "increase", "enhance" or "exceed" preferably relate to an increase or enhancement by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 80%, at least 100%, at least 200%, at least 500%, or even more.

[00579] According to the present disclosure, the term "peptide" comprises oligo- and polypeptides and refers to substances which comprise about two or more, about 3 or more, about 4 or more, about 6 or more, about 8 or more, about 10 or more, about 13 or more, about 16 or more, about 20 or more, and up to about 50, about 100 or about 150, consecutive amino acids linked to one another via peptide bonds. The term "protein" or "polypeptide" refers to large peptides, in particular peptides having at least about 150 amino acids, but the terms "peptide", "protein" and "polypeptide" are used herein usually as synonyms.

[00580] The term "priming" refers to a process wherein an immune effector cell such as a T cell has its first contact with its specific antigen and causes differentiation into effector cells such as effector T cells.

[00581] Terms such as "reduce", "decrease", "inhibit" or "impair" as used herein relate to an overall reduction or the ability to cause an overall reduction, preferably of at least 5%, at least 10%, at least 20%, at least 50%, at least 75% or even more, in the level. These terms include a complete or essentially complete inhibition, i.e., a reduction to zero or essentially to zero.

[00582] A "therapeutic protein" has a positive or advantageous effect on a condition or disease state of a subject when provided to the subject in a therapeutically effective amount. In one embodiment, a therapeutic protein has curative or palliative properties and may be administered to ameliorate, relieve, alleviate, reverse, delay onset of or lessen the severity of one or more symptoms of a disease or disorder. A therapeutic protein may have prophylactic properties and may be used to delay the onset of a disease or to lessen the severity of such disease or pathological condition. The term "therapeutic protein" includes entire proteins or peptides, and can also refer to therapeutically active fragments thereof. It can also include therapeutically active variants of a protein. Examples of therapeutically active proteins include, but are not limited to, antigens for vaccination and immunostimulants such as cytokines.

[00583] The term "T cell epitope" refers to a part or fragment of a protein that is recognized by a T cell when presented in the context of MHC molecules. The term "major histocompatibility complex" and the abbreviation "MHC" includes MHC class I and MHC class II molecules and relates to a complex of genes which is present in all vertebrates. MHC proteins or molecules are important for signaling between lymphocytes and antigen presenting cells or diseased cells in immune reactions, wherein the MHC proteins or molecules bind peptide epitopes and present them for recognition by T cell receptors on T cells. The proteins encoded by the MHC are expressed on the surface of cells, and display both self-antigens (peptide fragments from the cell itself) and non-self-antigens (e.g., fragments of invading microorganisms) to a T cell. In the case of class I MHC/peptide complexes, the binding peptides are typically about 8 to about 10 amino acids long although longer or shorter peptides may be effective. In the case of class II MHC/peptide complexes, the binding peptides are typically about 10 to about 25 amino acids long and are in particular about 13 to about 18 amino acids long, whereas longer and shorter peptides may be effective.

[00584] By "variant" herein is meant an amino acid sequence that differs from a parent amino acid sequence by virtue of at least one amino acid modification. The parent amino acid sequence may be a naturally occurring or wild type (WT) amino acid sequence, or may be a modified version of a wild type amino acid sequence. Preferably, the variant amino acid sequence has at least one amino acid modification compared to the parent amino acid sequence, e.g., from 1 to about 20 amino acid modifications, and preferably from 1 to about 10 or from 1 to about 5 amino acid modifications compared to the parent.

[00585] By "wild type" or "WT" or "native" herein is meant an amino acid sequence that is found in nature, including allelic variations. A wild type amino acid sequence, peptide or protein has an amino acid sequence that has not been intentionally modified.

[00586] A peptide and protein antigen which is provided to a subject according to the present disclosure by administering RNA encoding the peptide and protein antigen, i.e., a vaccine antigen, preferably results in the induction of an immune response, e.g., a humoral and/or cellular immune response in the subject being provided the peptide or protein antigen. Said immune response is preferably directed against a target antigen, in particular coronavirus S protein, in particular SARS-CoV-2 S protein. Thus, a vaccine antigen may comprise the target antigen, a variant thereof, or a fragment thereof. In one embodiment, such fragment or variant is immunologically equivalent to the target antigen. In the context of the present disclosure, the term "fragment of an antigen" or "variant of an antigen" means an agent which results in the induction of an immune response which immune response targets the antigen, i.e. a target antigen. Thus, the vaccine antigen may correspond to or may comprise the target antigen, may correspond to or may comprise a fragment of the target antigen or may correspond to or may comprise an antigen which is homologous to the target antigen or a fragment thereof. Thus, according to the present disclosure, a vaccine antigen may comprise an immunogenic fragment of a target antigen or an amino acid sequence being homologous to an immunogenic fragment of a target antigen. An "immunogenic fragment of an antigen" according to the present disclosure preferably relates to a fragment of an antigen which is capable of inducing an immune response against the target antigen. The vaccine antigen may be a recombinant antigen.

[00587] The peptide and protein antigen can be 2-100 amino acids, including for example, 5 amino acids, 10 amino acids, 15 amino acids, 20 amino acids, 25 amino acids, 30 amino acids, 35 amino acids, 40 amino acids, 45 amino acids, or 50 amino acids in length. In some embodiments, a peptide can be greater than 50 amino acids. In some embodiments, the peptide can be greater than 100 amino acids.

[00588] The peptide or protein antigen can be any peptide or protein that can induce or increase the ability of the immune system to develop antibodies and T cell responses to the peptide or protein.

[00589] In one embodiment, vaccine antigen is recognized by an immune effector cell. Preferably, the vaccine antigen if recognized by an immune effector cell is able to induce in the presence of appropriate costimulatory signals, stimulation, priming and/or expansion of the immune effector cell carrying an antigen receptor recognizing the vaccine antigen. In the context of the embodiments of the present disclosure, the vaccine antigen is preferably presented or present on the surface of a cell, preferably an antigen presenting cell. In one embodiment, an antigen is presented by a diseased cell such as a virus-infected cell. In one embodiment, an antigen receptor is a TCR which binds to an epitope of an antigen presented in the context of MHC. In one embodiment, binding of a TCR when expressed by T cells and/or present on T cells to an antigen presented by cells such as antigen presenting cells results in stimulation, priming and/or expansion of said T cells. In one embodiment, binding of a TCR when expressed by T cells and/or present on T cells to an antigen presented on diseased cells results in cytolysis and/or apoptosis of the diseased cells, wherein said T cells preferably release cytotoxic factors, e.g. perforins and granzymes.

[00590] In one embodiment, an antigen receptor is an antibody or B cell receptor which binds to an epitope in an antigen. In one embodiment, an antibody or B cell receptor binds to native epitopes of an antigen. [00591] In some embodiments, the present disclosure refers to a SARS-CoV-2 variant that is prevalent and/or rapidly spreading in a relevant jurisdiction. In some embodiments, such variants may be identified based on publicly available data (e.g., data provided in the GISAID Initiative database: httg^www^s^.or2, and/or data provided by the World Health Organization WHO (e.g., as provided at https://www.who.int/activities/tracking-SARS-CoV-2-variants). In some embodiments, such a variant refers to a variant disclosed herein.

[00592] For the purposes of the present disclosure, "variants" of an amino acid sequence (peptide, protein or polypeptide) comprise amino acid insertion variants, amino acid addition variants, amino acid deletion variants and/or amino acid substitution variants. The term "variant" includes all mutants, splice variants, posttranslationally modified variants, conformations, isoforms, allelic variants, species variants, and species homologs, in particular those which are naturally occurring. The term "variant" includes, in particular, fragments of an amino acid sequence.

[00593] Amino acid insertion variants comprise insertions of single or two or more amino acids in a particular amino acid sequence. In the case of amino acid sequence variants having an insertion, one or more amino acid residues are inserted into a particular site in an amino acid sequence, although random insertion with appropriate screening of the resulting product is also possible. Amino acid addition variants comprise amino- and/or carboxyterminal fusions of one or more amino acids, such as 1, 2, 3, 5, 10, 20, 30, 50, or more amino acids. Amino acid deletion variants are characterized by the removal of one or more amino acids from the sequence, such as by removal of 1, 2, 3, 5, 10, 20, 30, 50, or more amino acids. The deletions may be in any position of the protein. Amino acid deletion variants that comprise the deletion at the N-terminal and/or C-terminal end of the protein are also called N-terminal and/or C-terminal truncation variants. Amino acid substitution variants are characterized by at least one residue in the sequence being removed and another residue being inserted in its place. Preference is given to the modifications being in positions in the amino acid sequence which are not conserved between homologous proteins or peptides and/or to replacing amino acids with other ones having similar properties.

Preferably, amino acid changes in peptide and protein variants are conservative amino acid changes, i.e., substitutions of similarly charged or uncharged amino acids. A conservative amino acid change involves substitution of one of a family of amino acids which are related in their side chains. Naturally occurring amino acids are generally divided into four families: acidic (aspartate, glutamate), basic (lysine, arginine, histidine), nonpolar (alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), and uncharged polar (glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine) amino acids. Phenylalanine, tryptophan, and tyrosine are sometimes classified jointly as aromatic amino acids. In one embodiment, conservative amino acid substitutions include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid; asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.

[00594] Preferably the degree of similarity, preferably identity between a given amino acid sequence and an amino acid sequence which is a variant of said given amino acid sequence will be at least about 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%. The degree of similarity or identity is given preferably for an amino acid region which is at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100% of the entire length of the reference amino acid sequence. For example, if the reference amino acid sequence consists of 200 amino acids, the degree of similarity or identity is given preferably for at least about 20, at least about 40, at least about 60, at least about 80, at least about 100, at least about 120, at least about 140, at least about 160, at least about 180, or about 200 amino acids, in some embodiments continuous amino acids. In some embodiments, the degree of similarity or identity is given for the entire length of the reference amino acid sequence. The alignment for determining sequence similarity, preferably sequence identity can be done with art known tools, preferably using the best sequence alignment, for example, using Align, using standard settings, preferably EMBOSS: :needle, Matrix: Blosum62, Gap Open 10.0, Gap Extend 0.5.

[00595] "Sequence similarity" indicates the percentage of amino acids that either are identical or that represent conservative amino acid substitutions. "Sequence identity" between two amino acid sequences indicates the percentage of amino acids that are identical between the sequences. "Sequence identity" between two nucleic acid sequences indicates the percentage of nucleotides that are identical between the sequences.

[00596] The terms "% identical", "% identity" or similar terms are intended to refer, in particular, to the percentage of nucleotides or amino acids which are identical in an optimal alignment between the sequences to be compared. Said percentage is purely statistical, and the differences between the two sequences may be but are not necessarily randomly distributed over the entire length of the sequences to be compared. Comparisons of two sequences are usually carried out by comparing the sequences, after optimal alignment, with respect to a segment or "window of comparison", in order to identify local regions of corresponding sequences. The optimal alignment for a comparison may be carried out manually or with the aid of the local homology algorithm by Smith and Waterman, 1981, Ads App. Math. 2, 482, with the aid of the local homology algorithm by Neddleman and Wunsch, 1970, J. Mol. Biol. 48, 443, with the aid of the similarity search algorithm by Pearson and Lipman, 1988, Proc. Natl Acad. Sci. USA 88, 2444, or with the aid of computer programs using said algorithms (GAP, BESTFIT, FAST A, BLAST P, BLAST N and TFASTA in Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Drive, Madison, Wis.). In some embodiments, percent identity of two sequences is determined using the BLASTN or BLASTP algorithm, as available on the United States National Center for Biotechnology Information (NCBI) website (e.g., at blast. ncbi.nlm.nih.gov/Blast.cgi?PAGE_TYPE=BlastSearch&BLAST_SPEC=blast2seq&LINK_LOC=align2seq). In some embodiments, the algorithm parameters used for BLASTN algorithm on the NCBI website include: (i) Expect Threshold set to 10; (ii) Word Size set to 28; (iii) Max matches in a query range set to 0; (iv) Match/Mismatch Scores set to 1, -2; (v) Gap Costs set to Linear; and (vi) the filter for low complexity regions being used. In some embodiments, the algorithm parameters used for BLASTP algorithm on the NCBI website include: (i) Expect Threshold set to 10; (ii) Word Size set to 3; (iii) Max matches in a query range set to 0; (iv) Matrix set to BLOSUM62; (v) Gap Costs set to Existence: 11 Extension: 1; and (vi) conditional compositional score matrix adjustment.

[00597] Percentage identity is obtained by determining the number of identical positions at which the sequences to be compared correspond, dividing this number by the number of positions compared (e.g., the number of positions in the reference sequence) and multiplying this result by 100.

[00598] In some embodiments, the degree of similarity or identity is given for a region which is at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100% of the entire length of the reference sequence. For example, if the reference nucleic acid sequence consists of 200 nucleotides, the degree of identity is given for at least about 100, at least about 120, at least about 140, at least about 160, at least about 180, or about 200 nucleotides, in some embodiments continuous nucleotides. In some embodiments, the degree of similarity or identity is given for the entire length of the reference sequence.

[00599] Homologous amino acid sequences exhibit according to the present disclosure at least 40%, in particular at least 50%, at least 60%, at least 70%, at least 80%, at least 90% and preferably at least 95%, at least 98 or at least 99% identity of the amino acid residues.

[00600] The amino acid sequence variants described herein may readily be prepared by the skilled person, for example, by recombinant DNA manipulation. The manipulation of DNA sequences for preparing peptides or proteins having substitutions, additions, insertions or deletions, is described in detail in Sambrook et al. (1989), for example. Furthermore, the peptides and amino acid variants described herein may be readily prepared with the aid of known peptide synthesis techniques such as, for example, by solid phase synthesis and similar methods.

[00601] In one embodiment, a fragment or variant of an amino acid sequence (peptide or protein) is preferably a "functional fragment" or "functional variant". The term "functional fragment" or "functional variant" of an amino acid sequence relates to any fragment or variant exhibiting one or more functional properties identical or similar to those of the amino acid sequence from which it is derived, i.e., it is functionally equivalent. With respect to antigens or antigenic sequences, one particular function is one or more immunogenic activities displayed by the amino acid sequence from which the fragment or variant is derived. The term "functional fragment" or "functional variant", as used herein, in particular refers to a variant molecule or sequence that comprises an amino acid sequence that is altered by one or more amino acids compared to the amino acid sequence of the parent molecule or sequence and that is still capable of fulfilling one or more of the functions of the parent molecule or sequence, e.g., inducing an immune response. In one embodiment, the modifications in the amino acid sequence of the parent molecule or sequence do not significantly affect or alter the characteristics of the molecule or sequence. In different embodiments, the function of the functional fragment or functional variant may be reduced but still significantly present, e.g., immunogenicity of the functional variant may be at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of the parent molecule or sequence. However, in other embodiments, immunogenicity of the functional fragment or functional variant may be enhanced compared to the parent molecule or sequence.

[00602] An amino acid sequence (peptide, protein or polypeptide) "derived from" a designated amino acid sequence (peptide, protein or polypeptide) refers to the origin of the first amino acid sequence. Preferably, the amino acid sequence which is derived from a particular amino acid sequence has an amino acid sequence that is identical, essentially identical or homologous to that particular sequence or a fragment thereof. Amino acid sequences derived from a particular amino acid sequence may be variants of that particular sequence or a fragment thereof. For example, it will be understood by one of ordinary skill in the art that the antigens suitable for use herein may be altered such that they vary in sequence from the naturally occurring or native sequences from which they were derived, while retaining the desirable activity of the native sequences.

[00603] As used herein, an "instructional material" or "instructions" includes a publication, a recording, a diagram, or any other medium of expression which can be used to communicate the usefulness of the compositions and methods of the present disclosure. The instructional material of the kit of the present disclosure may, for example, be affixed to a container which contains the compositions of the present disclosure or be shipped together with a container which contains the compositions. Alternatively, the instructional material may be shipped separately from the container with the intention that the instructional material and the compositions be used cooperatively by the recipient.

[00604] "Isolated" means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not "isolated", but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is "isolated". An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell.

[00605] The term "recombinant" in the context of the present disclosure means "made through genetic engineering". Preferably, a "recombinant object" such as a recombinant nucleic acid in the context of the present disclosure is not occurring naturally.

[00606] The term "naturally occurring" as used herein refers to the fact that an object can be found in nature. For example, a peptide or nucleic acid that is present in an organism (including viruses) and can be isolated from a source in nature and which has not been intentionally modified by man in the laboratory is naturally occurring.

[00607] "Physiological pH" as used herein refers to a pH of about 7.5.

[00608] The term "genetic modification" or simply "modification" includes the transfection of cells with nucleic acid. The term "transfection" relates to the introduction of nucleic acids, in particular RNA, into a cell. For purposes of the present disclosure, the term "transfection" also includes the introduction of a nucleic acid into a cell or the uptake of a nucleic acid by such cell, wherein the cell may be present in a subject, e.g., a patient. Thus, according to the present disclosure, a cell for transfection of a nucleic acid described herein can be present in vitro or in vivo, e.g. the cell can form part of an organ, a tissue and/or an organism of a patient. According to the disclosure, transfection can be transient or stable. For some applications of transfection, it is sufficient if the transfected genetic material is only transiently expressed. RNA can be transfected into cells to transiently express its coded protein. Since the nucleic acid introduced in the transfection process is usually not integrated into the nuclear genome, the foreign nucleic acid will be diluted through mitosis or degraded. Cells allowing episomal amplification of nucleic acids greatly reduce the rate of dilution. If it is desired that the transfected nucleic acid actually remains in the genome of the cell and its daughter cells, a stable transfection must occur. Such stable transfection can be achieved by using virus-based systems or transposon-based systems for transfection.

Generally, nucleic acid encoding antigen is transiently transfected into cells. RNA can be transfected into cells to transiently express its coded protein.

[00609] The term "seroconversion" includes a ≥4-fold rise from before vaccination to 1-month post Dose 2. [00610] As used herein, the term "vaccine" refers to a composition that induces an immune response upon inoculation into a subject. In some embodiments, the induced immune response provides protective immunity.

Coronavirus

[00611] Coronaviruses are enveloped, positive-sense, single-stranded RNA ((+) ssRNA) viruses. They have the largest genomes (26-32 kb) among known RNA viruses and are phylogenetically divided into four genera (a, P, y, and 3), with betacoronaviruses further subdivided into four lineages (A, B, C, and D). Coronaviruses infect a wide range of avian and mammalian species, including humans. Some human coronaviruses generally cause mild respiratory diseases, although severity can be greater in infants, the elderly, and the immunocompromised. Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV), belonging to betacoronavirus lineages C and B, respectively, are highly pathogenic. Both viruses emerged into the human population from animal reservoirs within the last 15 years and caused outbreaks with high case-fatality rates. The outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes atypical pneumonia (coronavirus disease 2019; COVID-19) has raged in China since mid-December 2019, and has developed to be a public health emergency of international concern. SARS-CoV-2 (MN908947.3) belongs to betacoronavirus lineage B. It has at least 70% sequence similarity to SARS-CoV.

[00612] In general, coronaviruses have four structural proteins, namely, envelope (E), membrane (M), nucleocapsid (N), and spike (S). The E and M proteins have important functions in the viral assembly, and the N protein is necessary for viral RNA synthesis. The critical glycoprotein S is responsible for virus binding and entry into target cells. The S protein is synthesized as a single-chain inactive precursor that is cleaved by furin-like host proteases in the producing cell into two noncovalently associated subunits, SI and S2. The SI subunit contains the receptor-binding domain (RBD), which recognizes the host-cell receptor. The S2 subunit contains the fusion peptide, two heptad repeats, and a transmembrane domain, all of which are required to mediate fusion of the viral and host-cell membranes by undergoing a large conformational rearrangement. The SI and S2 subunits trimerize to form a large prefusion spike.

[00613] The S precursor protein of SARS-CoV-2 can be proteolytically cleaved into SI (685 aa) and S2 (588 aa) subunits. The SI subunit comprises the receptor-binding domain (RBD), which mediates virus entry into sensitive cells through the host angiotensin-converting enzyme 2 (ACE2) receptor.

SARS-CoV-2 Variants

[00614] Those skilled in the art are aware of various spike variants, and/or resources that document them. For example, the following strains, their SARS-CoV-2 S protein amino acid sequences and, in particular, modifications thereof compared to wildtype SARS-CoV-2 S protein amino acid sequence, e.g., as compared to SEQ ID NO: 1, are useful herein. As used herein, an S protein of a SARS-CoV-2 variant refers to an S protein that comprises at least one mutation that is present in the S protein of a SARS-CoV-2 varaint, as compared to the amino acid sequence of the S protein of the Wuhan strain (e.g., as compared to SEQ ID NO: 1).

[00615] Omicron has acquired numerous alterations (amino acid exchanges, insertions, or deletions) in the S glycoprotein, among which some are shared between all Omicron VOCs while others are specific to one or more Omicron sublineages. Antigenically, BA.2.12.1 exhibits high similarity with BA.2 but not BA.l, whereas BA.4 and BA.5 differ considerably from their ancestor BA.2 and even more so from BA.l, in line with their genealogy (A. Z. Mykytyn et al., "Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.l and BA.2 are antigenically distinct," Sci. Immunol. 7, eabq4450 (2022).). Major differences of BA.l from the remaining Omicron VOCs include A143-145, L212I, or ins214EPE in the S glycoprotein N-terminal domain and G446S or G496S in the receptor binding domain (RBD). Amino acid changes T376A, D405N, and R408S in the RBD are in turn common to BA.2 and its descendants but not found in BA.l. In addition, some alterations are specific for individual BA.2- descendant VOCs, including L452Q for BA.2.12.1 or L452R and F486V for BA.4 and BA.5 (BA.4 and BA.5 encode for the same S sequence). Most of these shared and VOC-specific alterations were shown to play an important role in immune escape from monoclonal antibodies and polyclonal sera raised against the wild-type S glycoprotein. In particular, the BA.4/BA.5-specific alterations are strongly implicated in immune escape of these VOCs (P. Wang et al., "Antibody resistance of SARS-CoV-2 variants B.1.351 and B.l.1.7. Nature 593, 130-135 (2021); Q. Wang et al., "Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, & BA.5. Nature 608, 603-608 (2022)). As of the filing date of the present application, the XBB group of variants, resulting from a recombination of BA.10.1 and BA.2.75, are the most prevalent SARS-CoV-2 variants of concern, representing the top three most prevalent strains in the US between May 28, 2023, and June 10, 2023.

B.l.1.7 ("Variant of Concern 202012/01" (VOC-202012/01)

[00616] B.l.1.7 (the "alpha variant") is a variant of SARS-CoV-2 which was first detected in October 2020 during the COVID-19 pandemic in the United Kingdom from a sample taken the previous month, and it quickly began to spread by mid-December. It is correlated with a significant increase in the rate of COVID-19 infection in United Kingdom; this increase is thought to be at least partly because of change N501Y inside the spike glycoprotein's receptor-binding domain, which is needed for binding to ACE2 in human cells. The B.l.1.7 variant is defined by 23 mutations: 13 non-synonymous mutations, 4 deletions, and 6 synonymous mutations (i.e., there are 17 mutations that change proteins and six that do not). The spike protein changes in B.l.1.7 include deletion 69-70, deletion 144, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H.

B.1.351 (501.V2)

[00617] B.1.351 lineage (the "Beta variant") and colloquially known as South African COVID-19 variant, is a variant of SARS-CoV-2. Preliminary results indicate that this variant may have an increased transmissibility. The B.1.351 variant is defined by multiple spike protein changes including: L18F, D80A, D215G, deletion 242-244, R246I, K417N, E484K, N501Y, D614G and A701V. There are three mutations of particular interest in the spike region of the B.1.351 genome: K417N, E484K, N501Y.

B.l.1.298 (Cluster 5)

[00618] B.l.1.298 was discovered in North Jutland, Denmark, and is believed to have been spread from minks to humans via mink farms. Several different mutations in the spike protein of the virus have been confirmed. The specific mutations include deletion 69-70, Y453F, D614G, I692V, M1229I, and optionally S1147L.

P.l (B.l.1.248)

[00619] Lineage B.l.1.248 (the "gamma variant"), known as the Brazil(ian) variant, is one of the variants of SARS-CoV-2 which has been named P.l lineage. P.l has a number of S-protein modifications [L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F] and is similar in certain key RBD positions (K417, E484, N501) to variant B.1.351 from South Africa.

B.l.617.2

[00620] The delta variant (also known as B.l.617.2 or G/478K.V1) was first documented in India. The delta variant has several point mutations that affect the spike protein, including P681R (a mutation position shared with alpha and adjacent to the furin cleavage site), and L452R, which is in the RBD and has been linked with increased binding to ACE2 and neutralizing antibody resistance. There is also a deletion in the spike protein at position 156/157.

B.1.427/B.1.429 (CAL.20C)

[00621] Lineage B.1.427/B.1.429 (the "epsilon variant"), also known as CAL.20C, is defined by the following modifications in the S-protein: S13I, W152C, L452R, and D614G of which the L452R modification is of particular concern. CDC has listed B.1.427/B.1.429 as "variant of concern".

B.l.525

[00622] B.l.525 (the "eta variant") carries the same E484K modification as found in the P.l, and B.1.351 variants, and also carries the same AH69/AV70 deletion as found in B.l.1.7, and B.l.1.298. It also carries the modifications D614G, Q677H and F888L.

B.l.526 [00623] B.1.526 (the "iota variant") was detected as an emerging lineage of viral isolates in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage are L5F, T95I, D253G, E484K, D614G, and A701V.

The following table shows an overview of exemplary SARS-CoV-2 strains which are or have been VOI/VOC.

Table 1: Overview of certain circulating SARS-CoV-2 strains which have been/are VOI/VOC

1.1.529

[00624] B.1.529 ("Omicron variant") was first detected in South Africa in November 2021. Omicron multiplies around 70 times faster than Delta variants, and quickly became the dominant strain of SARS-CoV-2 worldwide. Since its initial detection, a number of Omicron sublineages have arisen. Listed below are Omicron variants of concern, along with certain characteristic mutations associated with the S protein of each. The S protein of BA.4 and BA.5 have the same set of characteristic mutations, which is why the below table has a single row for"BA.4 or BA.5", and why the present disclosure refers to a "BA.4/5" S protein in some embodiments. Similarly, the S proteins of the BA.4.6 and BF.7 Omicron variants have the same set of characteristic mutations, which is why the below table has a single row for "BA.4.6 or BF.7").

[00625] The JN.l variant emerged in August 2023, in Luxemburg. It is a descendant of the BA.2.86 variant. BA.2.86 initially drew the attention of health authorities because it had a large number of S protein mutations as compared to previous variants (~30 more than other variants circulating at the time). BA.2.86 never came to dominate circulating SARS-CoV-2 variants, however. Unlike BA.2.86, the JN.l variant (and descendants thereof) has the ability to transmit efficiently between humans, an ability that is thought to be due to the acquisition of an L455S mutation in the S protein (position shown relative to SEQ ID NO: 1). The JN.l rapidly came to dominate SARS-CoV-2 variants, increasing from less than 5% in November 2023, to 60% of cases by January 2024. Since the initial emergence of the JN.l variant, descendants have continued to be identified, including the JN.l.2, JN.1.6, JN.l.7, KP.2, KP.3, and XEC variants, that have acquired further mutations relative to JN.l, and which are thought to further increase the infectivity and/or transmissibility of SARS-CoV-2 variants.

[00626] Since the emergence of JN.l, descendants of JN.l have arisen and quickly supplanted the JN.l variant. These JN.l descendants include "SLip" variants (including, e.g., JN.l.16), which include L455S and F456L mutations; and "FLiRT" variants (including, e.g., KS.1.1, KP.2), which include the mutations associated with SLip variants and an additional R346T mutation. FLuQE variants (e.g., KP.3.3), in turn, are descendants of the FLiRT variants, and include the same mutations plus an additional Q493E mutation. The 455 position has also continued to be a mutation hot spot, with "FLip" including mutations L455F and F456L.

[00627] The XEC variant is a hybrid of the KS.1.1 and KP.3.3 variants. A description of the emergence of the JN.l variant and descendants thereof, is provided, e.g., in E. Topol, "Are We FLiRTing With A New Covid Wave?," April 18, 2024, accessible at erictopol.substack.com/p/are-we-flirting-with-a-new-covid; and Sankaran, V. "New Covid XEC variant starting to spread in Europe - what we know," September 16, 2024, Independent, accessible at www.independent.co.uk/news/science/covid-variant-xec-europe-symptoms-b2613485.html.

Table 2A: Characteristic mutations of certain Omicron variants of concern

[00628] In some embodiments, RNA described herein comprises a nucleotide sequence encoding a SARS- CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of an Omicron variant (e.g., one or more (e.g., all of the) mutations associated with a given Omicron variant in Table 2A). In some embodiments, such RNA further comprise one or more mutations that stabilize the S protein in a pre-fusion confirmation (e.g., in some embodiments, such RNA further comprises proline residues at positions corresponding to residues 986 and 987 of SEQ ID NO: 1). In some embodiments, an RNA comprises a nucleotide sequence encoding a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) listed in Table 2A. In some such embodiments, an RNA comprises a nucleotide sequence encoding a SARS-CoV-2 S protein comprising one or more mutations from each of two or more variants listed in Table 2A. In some embodiments, an RNA comprises a nucleotide sequence encoding a SARS-CoV-2 S protein comprising one or more mutations (e.g., all of the mutations) identified in Table 2A as being characteristic of a certain Omicron variant (e.g., in some embodiments, an RNA comprises a nucleotide sequence encoding a SARS- CoV-2 S protein comprising each of the mutations listed in Table 2A as being characteristic of an Omicron BA.l, BA.2, BA.2.12.1, BA.4/5, BA.2.75, BA.2.75.1, BA.4.6, BQ.1.1, XBB, XBB.l, XBB.2, XBB.1.3, XBB.1.5, XBB.1.16, XBB.2.3, or XBB.2.3.2 variant).

[00629] In some embodiments, an RNA disclosed herein comprises a nucleotide sequence that encodes an immunogenic fragment of a SARS-Cov-2 S protein (e.g., RBD, truncated SI subdomain, or S2 domain), which comprises one or more mutations that are characteristic of a SARS-CoV-2 variant (e.g., an Omicron variant described herein). For example, in some embodiments, an RNA comprises a nucleotide sequence encoding the RBD of an S protein of a SARS-CoV-2 variant (e.g., a region of the S protein corresponding to amino acids 327 to 528 of SEQ ID NO: 1, and comprising one or more mutations that are characteristic of a variant of concern that lie within this region of the S protein). In some embodiments, a fragment of an S protein comprises one or more mutations associated with a JN.l, KP.2, or XEC variant, or a descendent thereof. A skilled artisan will understand that introducing one or more mutations that are associated with a SARS-CoV-2 variant into a fragment of an S protein (e.g., a truncated SI subdomain) will not substantially affect the general antigen properties of the fragment of the S protein, including, e.g., the ability of the fragment to induce a strong B cell response and high titers of neutralizing antibodies.

[00630] In some embodiments, an RNA comprises a nucleotide sequence encoding the RBD of an XBB.1.5 SARS-CoV-2 variant, wherein (i) the RBD comprises amino acids 323 to 524 of SEQ ID NO: 158 or an amino acid sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 158 and/or (ii) the RNA comprises nucleotides 967 to 1572 of SEQ ID NO: 160 or a nucleotide sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to nucleotides 967 to 1572 of SEQ ID NO: 160.

[00631] In some embodiments, an RNA comprises a nucleotide sequence encoding the RBD of an XBB.1.16 SARS-CoV-2 variant, wherein (i) the RBD comprises amino acids 323 to 524 of SEQ ID NO: 163 or an amino acid sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 163 and/or (ii) the RNA comprises nucleotides 967 to 1572 of SEQ ID NO: 165 or a nucleotide sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to nucleotides 967 to 1572 of SEQ ID NO: 165.

[00632] In some embodiments, an RNA comprises a nucleotide sequence encoding the RBD of an XBB.2.3 SARS-CoV-2 variant, wherein (i) the RBD comprises amino acids 323 to 524 of SEQ ID NO: 168 or an amino acid sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 168 and/or (ii) the RNA comprises nucleotides 967 to 1572 of SEQ ID NO: 170 or a nucleotide sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to nucleotides 967 to 1572 of SEQ ID NO: 170.

[00633] In some embodiments, an RNA comprises a nucleotide sequence encoding the RBD of an XBB.2.3.2 SARS-CoV-2 variant, wherein (i) the RBD comprises amino acids 323 to 524 of SEQ ID NO: 173 or an amino acid sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 173 and/or (ii) the RNA comprises nucleotides 967 to 1572 of SEQ ID NO: 175 or a nucleotide sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to nucleotides 967 to 1572 of SEQ ID NO: 175.

[00634] In some embodiments, an RNA comprises a nucleotide sequence encoding the RBD of an XBB.1.16 SARS-CoV-2 variant, wherein (i) the amino acid sequence of the RBD comprises amino acids 323 to 524 of SEQ ID NO: 163 and/or (ii) the RNA comprises a nucleotide sequence that is at least 70% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to nucleotides 967 to 1572 of SEQ ID NO: 165.

[00635] In some embodiments, an RNA encodes a SARS-CoV-2 S protein comprising a subset of the mutations listed in Table 2A. In some embodiments, an RNA encodes a SARS-CoV-2 S protein comprising the mutations listed in Table 2A that are most prevalent in a certain variant (e.g., mutations that have been detected in at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% of sequences collected to date for a given variant). Mutation prevalence can be determined, e.g., based on published sequences (e.g., sequences that are collected and made available to the public by GISAID).

[00636] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations that are characteristic of a BA.4/5 variant. In some embodiments, the one or more mutations characteristic of a BA.4/5 variant include T19I, A24-26, A27S, A69/70, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations that are characteristic of a BA.4/5 variant and excludes R408S. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.4/5 variant and excludes R408S.

[00637] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) mutations characteristic of a BA.2.75 variant. In some embodiments, the one or more mutations characteristic of a BA.2.75 variant include T19I, A24-26, A27S, G142D, K147E, W152R, F157L, I210V, V213G, G257S, G339H, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, G446S, N460K, S477N, T478K, E484A, Q498R, N501Y, Y505H D614G, H655Y, N679K, P681H, N764K, Q954H, and N969K, or any combination thereof. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.2.75 variant, and which excludes N354D. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.2.75 variant, and which excludes D796Y. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.2.75 variant, and which excludes D796Y and N354D.

[00638] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of a BA.2.75.2 variant. In some embodiments, the one or more mutations characteristic of a BA.2.75.2 variant include T19I, A24-26, A27S, G142D, K147E, W152R, F157L, I210V, V213G, G257S, G339H, R346T, N354D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, G446S, N460K, S477N, T478K, E484A, F486S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K, and D1199N, or any combination thereof. In some embodiments, RNA described herein encodes a SARS- CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.2.75.2 variant, and which excludes R346T.

[00639] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of a BA.4.6 or BF.7 variant. In some embodiments, the one or more mutations characteristic of a BA.4.6 or BF.7 variant include T19I, A24-26, A27S, A69/70, G142D, V213G, G339D, R346T, S371F, S373P, S375F, T376A, D405N, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.4.6 or BF.7 variant, and which exclude R408S. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.4.6 or BF.7 variant, and which exclude N658S. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BA.4.6 or BF.7 variant, and which exclude N658S and R408S.

[00640] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB variant. In some embodiments, the one or more mutations characteristic of an Omicron XBB variant include T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, V213E, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486S, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof. In some embodiments, the one or more mutations characteristic of an Omicron XBB variant include T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, V213E, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486S, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof.

[00641] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB.l variant. In some embodiments, the one or more mutations characteristic of an Omicron XBB.l variant include G252V. In some embodiments, the one or more mutations characteristic of an Omicron XBB.l variant include T19I, A24-26, A27S, V83A, G142D, Al 44, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486S, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of an Omicron XBB.l variant and which exclude Q493R. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of an Omicron XBB variant and which exclude Q493R and G252V.

[00642] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB.2 variant. In some embodiments, the one or more mutations characteristic of an Omicron XBB.2 variant include D253G. In some embodiments, the one or more mutations characteristic of an Omicron-XBB.2 variant include T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, V213E, D253G, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486S, F490S, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof.

[00643] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB.2.3 variant (e.g., as listed in the above Table 2A). In some embodiments, the one or more mutations characteristic of an Omicron XBB.2.3 variant include one or more mutations characteristic of an XBB variant and one or more of D253G, F486P, and P521S. In some embodiments, the one or more mutations characteristic of an Omicron XBB.2.3 variant include T19I, A24-26, A27S, V83A, G142D, A144, H146Q, Q183E, V213E, D253G, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486P, F490S, Q498R, N501Y, P521S, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof.

[00644] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB.2.3.2 variant (e.g., as listed in the above Table 2A). In some embodiments, the one or more mutations characteristic of an Omicron XBB.2.3.2 variant include one or more mutations characteristic of an XBB variant and one or more of G184V, D253G, F486P, and P521S. In some embodiments, the one or more mutations characteristic of an Omicron XBB.2.3 variant include T19I, A24-26, A27S, V83A, G142D, Al 44, H146Q, Q183E, G184V, V213E, D253G, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486P, F490S, Q498R, N501Y, P521S, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof. [00645] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB.1.3 variant. In some embodiments, the one or more mutations characteristic of an Omicron XBB.1.3 variant include G252V and A484T. In some embodiments, the one or more mutations characteristic of an Omicron XBB.1.3 variant include T19I, A24-26, A27S, V83A, G142D, Al 44, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, A484T, F486S, F490S, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof.

[00646] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB.1.5 variant. In some embodiments, the one or more mutations characteristic of an Omicron XBB.1.5 variant include F486P. In some embodiments, the one or more mutations characteristic of an Omicron XBB.1.5 variant include T19I, A24-26, A27S, V83A, G142D, Al 44, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, S486P, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof. In some embodiments, the one or more mutations characteristic of an Omicron XBB.1.5 variant include T19I, A24-26, A27S, V83A, G142D, A145, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486P, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof.

[00647] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of an Omicron XBB.1.16 variant. In some embodiments, the one or more mutations characteristic of an Omicron XBB.1.16 variant include E180V and K478R. In some embodiments, the one or more mutations characteristic of an Omicron XBB.1.16 variant include T19I, A24-26, A27S, V83A, G142D, A145, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, S486P, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof.

[00648] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations that are characteristic of a BQ.1.1 variant. In some embodiments, the one or more mutations characteristic of a BQ.1.1 variant include T19I, A24-26, A27S, A69/70, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, K444T, L452R, N463K, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, or any combination thereof. In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations (including, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) that are characteristic of a BQ.1.1 variant.

[00649] In some embodiments, RNA described herein encodes a SARS-CoV-2 S protein comprising one or more mutations characteristic of a JN.l, JN.1.2, JN.1.6, KP.2, KP.3, XEC and/or JN.1.7 variant (e.g., one or more mutations described herein). In some embodiments, the one or more mutations include a mutation at a position corresponding to position 455 of SEQ ID NO: 1 (e.g., L455S). In some embodiments, the one or more mutations include mutations at a position corresponding to position 455 of SEQ ID NO: 1 (e.g., L455F). In some embodiments, the one or more mutations include a mutation at a position corresponding position 456 of SEQ ID NO: 1 (e.g., F456L). In some embodiments, the one or more mutations include mutations at positions corresponding positions 455 and 456 of SEQ ID NO: 1 (e.g., F456L and L455F). In some embodiments, the one or mutations include a mutation at a position corresponding to position 346 of SEQ ID NO: 1 (e.g., R346T). In some embodiments, the one or more mutations include a mutation at a position corresponding to position 1104 of SEQ ID NO: 1 (e.g., V1104L). In some embodiments, the one or more mutations include mutations at positions corresponding to positions 346 and 1104 of SEQ ID NO: 1 (e.g., R346T and V1104L).

[00650] In some embodiments, one or more mutations characteristic of a KP.2 variant include one or more of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 or more of (e.g., all of) insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145, F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, R346T, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, F456L, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, V1104L, and P1143L, where mutations are indicated relative to SEQ ID NO: 1. In some embodiments, one or mutations characteristic of a KP.2 variant include R346T and V1104L, where positions are indicated relative to SEQ ID NO: 1. In some embodiments, one or mutations characteristic of a KP.2 variant include R346T, F456L, and/or V1104L, where positions are indicated relative to SEQ ID NO: 1.

[00651] In some embodiments, one or more mutations characteristic of a KP.3 variant include one or more of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,

31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,

60, 61, 62, 63. 64, 65 or more of (e.g., all of) insl6MPLF, T19, A24-26, A27S, S50L, A69/70, V127F, G142D, A144, F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, F456L, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q493E, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, V1104L, P1143L, or any combination thereof. In some embodiments one or more mutations characteristic of a KP.3 variant include F456L, Q493E, and/or V1104L, wherein positions are indicated relative to SEQ ID NO: 1.

[00652] In some embodiments, one or more mutations characteristic of a XEC variant include one or more of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,

32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60,

61, 62, 63, 64, 65, 67 or more of (e.g., all of) insl6MPLF, T19I, R21T, T22N, A24-26, A27S, S50L, A69-70, V127F, G142D, A145, F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, R346T, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, F456L, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, V1104L, P1143L, where mutations are indicated relative to SEQ ID NO: 1. In some embodiments one or more mutations characteristic of a XEC variant include T22N, F59S, F456L, Q493E, and/or V1104L, wherein positions are indicated relative to SEQ ID NO: 1. [00653] In some embodiments, one or more mutations characteristic of a JN.l variant include one or more of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 or more of (e.g., all of) insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145, F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, P1143L, or any combination thereof, where mutations are indicated relative to SEQ ID NO: 1. In some embodiments, one or more mutations characteristic of a JN.l variant include insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145. F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, and P1143L, relative to SEQ ID NO: 1. In some embodiments, one or mutations characteristic of a JN.l variant include L455S.

[00654] In some embodiments, a fragment of an S protein (e.g., an RBD or a truncated SI polypeptide described herein) comprises one or more mutations associated with a JN.2 variant. In some embodiments, a fragment of an S protein comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or more of the following list of mutations: insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145, F157S, R158G, A201, L202I, V203G, L206F, H245N, A264D, I332V, G339H, R346T, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, and P1143L. In some embodiments, a fragment of an S protein comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or more of the following list of mutations: insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, Al 45, F157S, R158G, A201, L202I, V203G, L206F, H245N, A264D, I332V, G339H, R346T, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, and Y505H.

[00655] In some embodiments, one or more mutations characteristic of a JN.l.2 variant include one or more of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 or more of (e.g., all of) insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145, F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, P1143L, and M1229I, where mutations are indicated relative to SEQ ID NO: 1. In some embodiments, one or more mutations characteristic of a JN.l.2 variant include M1229I, where position is indicated relative to SEQ ID NO: 1.

[00656] In some embodiments, one or more mutations characteristic of a JN.1.6 variant include one or more of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 or more of (e.g., all of) insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145. F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, R346T, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, and P1143L, where mutations are indicated relative to SEQ ID NO:

1. In some embodiments, one or more mutations characteristic of a JN.1.6 variant include R346T.

[00657] In some embodiments, one or more mutations characteristic of a JN.1.7 variant include one or more of (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,

31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 or more of (e.g., all of) insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145. F157S, R158G, A211, L212I, V213G, L216F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, T572I, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, P1143L, and E1150D, where mutations are indicated relative to SEQ ID NO: 1.

[00658] In some embodiments, a fragment of an S protein (e.g., an RBD or a truncated SI polypeptide described herein) comprises one or more mutations associated with a JN.6 variant. In some embodiments, a fragment of an S protein comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or more of the following list of mutations: insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145. F157S, R158G, A201, L202I, V203G, L206F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, T572I, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, P1143L, and E1150D. In some embodiments, a fragment of an S protein comprises one or more (e.g., 1,

2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or more of the following list of mutations: insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145. F157S, R158G, A201, L202I, V203G, L206F, H245N, A264D, I332V, G339H, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H.

[00659] In some embodiments, a fragment of an S protein (e.g., an RBD or a truncated SI polypeptide described herein) comprises one or more mutations associated with a JN.6 variant. In some embodiments, a fragment of an S protein comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or more of the following list of mutations: insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145, F157S, R158G, A201, L202I, V203G, L206F, H245N, A264D, I332V, G339H, R346T, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, F456L, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, Y505H, E554K, A570V, D614G, P621S, H655Y, N679K, P681R, N764K, D796Y, S939F, Q954H, N969K, V1104L, P1143L. In some embodiments, a fragment of an S protein comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31,

32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or more of the following list of mutations: insl6MPLF, T19I, R21T, A24-26, A27S, S50L, A69-70, V127F, G142D, A145, F157S, R158G, A201, L202I, V203G, L206F, H245N, A264D, I332V, G339H, R346T, K356T, S371F, S373P, S375F, T376A, R403K, D405N, R408S, K417N, N440K, V445H, G446S, N450D, L452W, L455S, F456L, N460K, S477N, T478K, N481K, A483, E484K, F486P, Q498R, N501Y, and Y505H.

Immunogenic Portions of Coronavirus S Proteins

[00660] The present disclosure comprises the use of RNA encoding an amino acid sequence comprising SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof. Thus, the RNA encodes a peptide or protein comprising at least an epitope SARS-CoV-2 S protein or an immunogenic variant thereof for inducing an immune response against coronavirus S protein, in particular SARS-CoV-2 S protein in a subject. The amino acid sequence comprising SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof (i.e., the antigenic peptide or protein) is also designated herein as "vaccine antigen", "peptide and protein antigen", "antigen molecule" or simply "antigen". The SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof is also designated herein as "antigenic peptide or protein" or "antigenic sequence". [00661] The SARS-CoV-2 coronavirus full length spike (S) protein from the first detected SARS-CoV-2 strain (referred to as the Wuhan strain herein) consists of 1273 amino acids and has the amino acid sequence according to SEQ ID NO: 1: MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLP FNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNWIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEY VSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSG WTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFN ATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDD FTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVW LSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVI TPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPR RARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTG IAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFN GLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSST ASALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAAT KMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFY EPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNES LIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT (SEQ ID NO: 1)

[00662] For purposes of the present disclosure, the above sequence is considered the wildtype or Wuhan SARS-CoV-2 S protein amino acid sequence. Unless otherwise indicated, position numberings in a SARS-CoV-2 S protein given herein are in relation to the amino acid sequence according to SEQ ID NO: 1. One of skill in the art reading the present disclosure will understand and be able to determine corresponding positions in a SARS-CoV-2 S protein variant sequence from locations of positions provided relative to the amino acid sequence of SEQ ID NO: 1 (i.e., a person of skill in the art provided positions relative to SEQ ID NO: 1, or another variant, will be able to determine corresponding positions in the S protein sequence of another SARS-CoV-2 variant or a fragment thereof). One of skill in the art will also understand that a fragment of a SARS-CoV-2 S protein that comprises one or more mutations of a variant, comprises only those mutations that fall within the fragment region. For example, if a truncated SI subdomain comprises an amino acid sequence corresponding to amino acids 20-528 of SEQ ID NO: 1 and comprises one or more mutations of a SARS-CoV-2 variant, one of skill in the art will understand that the truncated SI subdomain comprises only those mutations located within the corresponding region of the SARS-CoV-2 variant.

[00663] In some embodiments, a fragment of an S protein (e.g., a truncated SI domain, including, e.g., a sequence comprising amino acids 20-528 of SEQ ID NO: 1, 17-528 of SEQ ID NO: 1, 14-528 of SEQ ID NO: 1, 20- 541 of SEQ ID NO: 1, 17-528 of SEQID NO: 1, or 14-528 of SEQ ID NO: 1) includes 1 or more mutations associated with a SARS-CoV-2 variant (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 25, 36 or more (e.g., all)), to the extent they are present in the corresponding fragment of the S protein of the SARS-CoV-2 variant.

[00664] In specific embodiments, full length spike (S) protein encoded by an RNA described herein can be modified in such a way that the prototypical prefusion conformation is stabilized. Certain mutations that stabilize a prefusion confirmation are known in the art, e.g., as disclosed in WO 2021243122 A2 and Hsieh, Ching-Lin, et al. ("Structure-based design of prefusion-stabilized SARS-CoV-2 spikes," Science 369.6510 (2020): 1501-1505), the contents of each which are incorporated by reference herein in their entirety. In some embodiments, a SARS- CoV-2 S protein may be stabilized by introducing one or more proline mutations. In some embodiments, a SARS- CoV-2 S protein comprises a proline substitution at positions corresponding to residues 986 and/or 987 of SEQ ID NO: 1. In some embodiments, a SARS-CoV-2 S protein comprises a proline substitution at one or more positions corresponding to residues 817, 892, 899, and 942 of SEQ ID NO: 1. In some embodiments, a SARS-CoV-2 S protein comprises a proline substitution at positions corresponding to each of residues 817, 892, 899, and 942 of SEQ ID NO: 1. In some embodiments, a SARS-CoV-2 S protein comprises a proline substitution at positions corresponding to each of residues 817, 892, 899, 942, 986, and 987 of SEQ ID NO: 1.

[00665] In some embodiments, stabilization of the prefusion conformation may be obtained by introducing two consecutive proline substitutions at residues 986 and 987 in the full length spike protein. Specifically, spike (S) protein stabilized protein variants are obtained in a way that the amino acid residue at position 986 is exchanged to proline and the amino acid residue at position 987 is also exchanged to proline. In one embodiment, a SARS-CoV-2 S protein variant wherein the prototypical prefusion conformation is stabilized comprises the amino acid sequence shown in SEQ ID NO: 7: MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLP FNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNWIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEY VSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSG WTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFN ATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDD FTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRWV LSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVI TPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPR RARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTG lAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFN GLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSST ASALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAAT KMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFY EPQIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNES LIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT (SEQ ID NO: 7)

[00666] In one embodiment, the vaccine antigen described herein comprises, consists essentially of or consists of a spike protein (S) of SARS-CoV-2, a variant thereof, or an immunogenic fragment thereof (e.g., but not limited to RBD).

[00667] In one embodiment, the vaccine antigen comprises, consists essentially of or consists of SARS-CoV- 2 spike SI fragment (SI) (the SI subunit of a spike protein (S) of SARS-CoV-2), a variant thereof, or a fragment thereof.

[00668] In one embodiment, a vaccine antigen comprises, consists essentially of or consists of the receptor binding domain (RBD) of the SI subunit of a spike protein (S) of SARS-CoV-2, a variant thereof, or a fragment thereof. The amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 1, a variant thereof, or a fragment thereof is also referred to herein as "RBD" or "RBD domain".

[00669] In one embodiment, a vaccine antigen comprises the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 1, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 1, or an immunogenic fragment of the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 1, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 1. In one embodiment, a vaccine antigen comprises the amino acid sequence of amino acids 327 to 528 Of SEQ ID NO: 1.

[00670] In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein lacks certain features that are present in the full length polypeptide.

[00671] In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein lacks regions of the S protein other than the RBD, the NTD, or the NTD and RBD (where the secretory signal peptide present in the NTD is optionally replaced with a heterologous secretory signal peptide). For example, in some embodiments, an immunogenic portion of a SARS-CoV-2 S protein lacks a full S2 domain. In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein lacks the entire S2 domain. In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein lacks a full S2 domain, but comprises certain sequences that can improve immunogenicity and/or stability of an immunogenic portion (e.g., in some embodiments, an immunogenic portion lacks a full S2 domain but retains a TM sequence and optionally a sequence that is endogenously C-terminally adjacent to the TM sequence in a SARS-CoV-2 S protein).

[00672] In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein comprises an N-terminal domain (NTD) of the S protein. In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein comprises a receptor binding domain (RBD) of the S protein. In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein comprises an SI domain of the S protein or a truncated SI subdomain.

[00673] In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein comprises an RBD and an NTD and omits other features of the SI domain, optionally wherein the endogenous secretory signal peptide in the NTD is replaced with a heterologous secretory signal peptide.

[00674] SARS-CoV-2 S proteins are well characterized, and a person of skill in the art will be able to determine which portions of an S protein sequence correspond to immunogenic portions discussed herein (e.g., which portions of an S protein sequence correspond to the NTD, the RBD, the SI, and the S2 domains).

[00675] In some embodiments, an RBD comprises a portion of SEQ ID NO: 1 corresponding to the amino acid sequence between (i) about amino acid 317 to about amino acid 330 (inclusive) of SEQ ID NO: 1, and (ii) about amino acid 528 and about amino acid 541 (inclusive) of SEQ ID NO: 1, or a corresponding region in an S protein of a SARS-CoV-2 variant. In some embodiments, the N-terminal residue of an RBD corresponds to about position 317 in SEQ ID NO: 1, or a corresponding amino acid in an S protein of a SARS-CoV-2 variant. In some embodiments, the N-terminal residue of an RBD corresponds to about position 327 in SEQ ID NO: 1, or a corresponding amino acid in an S protein of a SARS-CoV-2 variant. In some embodiments, the N-terminal residue of an RBD corresponds to about position 330 of SEQ ID NO: 1, or a corresponding amino acid in an S protein of a SARS-CoV-2 variant. In some embodiments, the C-terminal residue of an RBD corresponds to about position 528 of SEQ ID NO: 1, or a corresponding residue in an S protein of a SARS-CoV-2 variant. In some embodiments, the C-terminal residue of an RBD corresponds to about position 541 of SEQ ID NO: 1, or a corresponding residue in an S protein of a SARS-CoV-2 variant. In some embodiments the N-terminal residue of an RBD corresponds to an amino acid between amino acids 317 and 330 (inclusive) of SEQ ID NO: 1 and the C-terminal residue of an RBD corresponds to an amino acid between amino acids 528 and 541 (inclusive) of SEQ ID NO: 1. In some embodiments, an RBD of a SARS-CoV-2 S protein comprises residues 327 to 528 of SEQ ID NO: 1, residues 330 to 528 of SEQ ID NO: 1, residues 330 to 541 of SEQ ID NO: 1, or residues 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

[00676] In some embodiments, an RBD of SARS-CoV-2 comprises the amino acid sequence: VRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNFAPFFAFKCYGVSPTKLNDLCFTNVYADSFVIRGNEVSQIAP GQTGNIADYNYKLPDDFTGCVIAWNSNKLDSKPSGNYNYLYRLFRKSKLKPFERDISTEIYQAGNKPCNGVAGPNCYSPLQSYGF RPTYGVGHQPYRWVLSFELLHAPATVCGPK (SEQ ID NO: 3), or a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.

[00677] In some embodiments, an RBD of SARS-CoV-2 comprises the amino acid sequence: PNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNFAPFFAFKCYGVSPTKLNDLCFTNVYADSFVIRGNEVSQIAPGQT GNIADYNYKLPDDFTGCVIAWNSNKLDSKPSGNYNYLYRLFRKSKLKPFERDISTEIYQAGNKPCNGVAGPNCYSPLQSYGFRPT YGVGHQPYRWVLSFELLHAPATVCGPK (SEQ ID NO: 325), or a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.

[00678] In some embodiments, an RBD of SARS-CoV-2 comprises the amino acid sequence: VRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAP GQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGF QPTNGVGYQPYRVVVLSFELLHAPATVCGPK (SEQ ID NO: 4), or a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.

[00679] In some embodiments, an RBD of SARS-CoV-2 comprises the amino acid sequence: VRFPNITNLCPFDEVFNATRFASVYAWNRKRISNCVADYSVLYNLAPFFTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAP GQTGNIADYNYKLPDDFTGCVIAWNSNKLDSK(SEQ ID NO: 326), or a sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.

[00680] In some embodiments, an immunogenic fragment of a SARS-CoV-2 S protein comprises an N- terminal domain ("NTD") polypeptide (i.e., a polypeptide that includes a spike protein NTD polypeptide, an immunogenic fragment thereof, or a variant thereof, e.g., as described herein). In some embodiments, an NTD lacks an endogenous SARS-CoV-2 secretory signal peptide, and a polypeptide instead comprises a heterologous secretory signal peptide (i.e., a secretory signal peptide that is not from a SARS-CoV-2 S protein).

[00681] In some embodiments, an NTD comprises a portion of SEQ ID NO: 1 corresponding to the amino acid sequence between about amino acid 1 and about amino acid 20 of SEQ ID NO: 1 and about amino acid 302 to 318 (inclusive) of SEQ ID NO: 1, or a corresponding region in an S protein of a SARS-CoV-2 variant. In some embodiments, the N-terminal residue of an RBD corresponds to about position 317 in SEQ ID NO: 1, or a corresponding amino acid in an S protein of a SARS-CoV-2 variant. In some embodiments, the N-terminal residue of an NTD corresponds to about position 1 in SEQ ID NO: 1, or a corresponding amino acid in an S protein of a SARS-CoV-2 variant. In some embodiments, the N-terminal residue of an NTD corresponds to about position 14 of SEQ ID NO: 1, or a corresponding amino acid in an S protein of a SARS-CoV-2 variant. In some embodiments, the C-terminal residue of an NTD corresponds to about position 17 of SEQ ID NO: 1, or a corresponding residue in an S protein of a SARS-CoV-2 variant. In some embodiments, the C-terminal residue of an NTD corresponds to about position 20 of SEQ ID NO: 1, or a corresponding residue in an S protein of a SARS-CoV-2 variant. In some embodiments, the C-terminal residue of an NTD corresponds to about position 302 of SEQ ID NO: 1, or a corresponding residue in an S protein of a SARS-CoV-2 variant. In some embodiments, the C-terminal residue of an NTD corresponds to about position 303 of SEQ ID NO: 1, or a corresponding residue in an S protein of a SARS-CoV-2 variant. In some embodiments, the C-terminal residue of an NTD corresponds to about position 318 of SEQ ID NO: 1, or a corresponding residue in an S protein of a SARS-CoV-2 variant. In some embodiments the N-terminal residue of an NTD corresponds to an amino acid between amino acids 1 and 20 (inclusive) of SEQ ID NO: 1 and the C-terminal residue of an NTD corresponds to an amino acid between amino acids 302-318 (inclusive) of SEQ ID NO: 1. In some embodiments, an NTD of a SARS-CoV-2 S protein comprises residues 1 to 302 of SEQ ID NO: 1, residues 1 to 302 of SEQ ID NO: 1, residues 1 to 303 of SEQ ID NO: 1, residues 14 to 318 of SEQ ID NO: 1, residues 14 to 302 of SEQ ID NO: 1, residues 14 to 302 of SEQ ID NO: 1, residues 14 to 303 of

SEQ ID NO: 1, residues 14 to 318 of SEQ ID NO: 1, residues 17 to 302 of SEQ ID NO: 1, residues 17 to 302 of

SEQ ID NO: 1, residues 17 to 303 of SEQ ID NO: 1, residues 17 to 318 of SEQ ID NO: 1, residues 20 to 302 of

SEQ ID NO: 1, residues 20 to 302 of SEQ ID NO: 1, residues 20 to 303 of SEQ ID NO: 1, or residues 20 to 318 of

SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

[00682] In some embodiments, an NTD polypeptide comprises a sequence corresponding to amino acids 14- 209, 14-303, 20-318 or 20-302 of SEQ ID NO: 1, variants thereof, or immunogenic fragments or variants thereof. [00683] In some embodiments, an immunogenic portion of a SARS-CoV-2 S protein comprises an S2 domain and lacks other regions of the S protein (including, e.g., the RBD and/or the NTD, or or other portions of the S2 domain).

[00684] Among other things, the present application provides an insight that, in some embodiments, an RNA encoding an S2 polypeptide, or an immunogenic fragment or variant thereof (e.g., an immunogenic fragment described herein) can produce an improved immune response as compared to RNA encoding an appropriate reference antigen (e.g., as compared to RNA encoding a SARS-CoV-2 RBD, SARS-CoV-2 NTD or a full length SARS-CoV-2 S protein). In particular, in some embodiments, an RNA encoding an S2 polypeptide or an immunogenic fragment and/or variant thereof can produce a more broadly cross-neutralizing immune response (e.g., induce higher titers of antibodies that can bind and/or neutralize a greater number of SARS-CoV-2 strains or variants) as compared to an appropriate reference antigen or an RNA (e.g., mRNA) encoding an appropriate reference antigen. [00685] Without wishing to be bound by theory, S2 polypeptides are highly conserved among panbetacoronaviruses, and also comprise broadly neutralizing epitopes. Thus, in some embodiments, an RNA encoding an S2 polypeptide, or an immunogenic fragment thereof, can elicit production of antibodes that can bind conserved neutralization eptiopes (e.g., epitopes that produce a neutralizing response), therefore resulting in an immune response that is more broadly cross-neutralizing (e.g., can induce a neutralization response against different betacoronaviruses, different sarbecoviruses, and/or different SARS-CoV-2 strains or varaints) as compared to RNA encoding an appropriate reference antigen (e.g, an RNA encoding a polypeptide that lacks the S2 domain and/or as compared to RNA that encodes a polypeptide comprising a full-length S protein). In some embodiments, an RNA encoding a polypeptide comprising the S2 polypeptide (and not the full length S protein), or an immunogenic fragment and/or variant thereof, can produce an improved immune response against the S2 polypeptide (or an immunogenic fragment and/or variant thereof) by increasing the accessibility of the S2 polypeptide (improved as compared to, e.g., an RNA encoding a full length S protein).

[00686] In some embodiments, an S2 domain of a SARS-CoV-2 S protein comprises amino acids 679 to 1273 of SEQ ID NO: 1, or a corresponding region in an S protein of a SARS-CoV-2 variant. In some embodiments, an S2 domain of a SARS-CoV-2 S protein comprises amino acids 684 to 1273 of SEQ ID NO: 1, or a corresponding region in an S protein of a SARS-CoV-2 variant. In some embodiments, an S2 domain of a SARS-CoV-2 S protein comprises amino acids 686 to 1273 of SEQ ID NO: 1, or a corresponding region in an S protein of a SARS-CoV-2 variant.

[00687] In some embodiments, an S2 domain does not comprise a SARS-CoV-2 transmembrane region (e.g., does not comprise amino acids and is soluble. In some embodiments, an S2 domain lacks residue 1207 and residues C-terminal thereto of SEQ ID NO: 1 or a corresponding region of an S protein of a SARS-CoV-2 variant. In some embodiments, an S2 domain lacks residue 1213 and residues C-terminal thereto of SEQ ID NO: 1 or a corresponding region of an S protein of a SARS-CoV-2 variant. In some embodiments, an S2 domain lacks residue 1211 and residues C-terminal thereto of SEQ ID NO: 1 or a corresponding region of an S protein of a SARS-CoV-2 variant. In some embodiments, an S2 domain comprises amino acid 686-1213 of SEQ ID NO: 1, 686-1211 of SEQ ID NO: 1, amino acids 687-1206 of SEQ ID NO: 1, or amino acids 687-1211 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant, optionally wherein the S2 domain compries one or more mutations that stabilize the S2 polypeptide.

[00688] In some embodiments, an S2 domain comprises an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYH LM SFPQSAPHGWFLHVTYVPAQEKN FTTAPAICH DG KAH FPREGVFVSNGTHWFVTQRN FYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIKWP, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[00689] In some embodiments, an S2 domain comprises an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[00690] In some embodiments, an S2 domain comprises an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[00691] In some embodiments, an S2 domain comprises an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKY, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[00692] In some embodiments, an S2 domain or a fragment thereof comprises a stem helix and/or a fusion peptide of an S2 polypeptide.

[00693] In some embodiments, a fusion peptide comprises a sequence of PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 varaint. In some embodiments, a fusion peptide comprises a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD. In some embodiments, a fusion peptide comprises a sequence having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications relative to PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD.

[00694] In some embodiments, a stem helix comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 varaint. In some embodiments, a stem helix comprises a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to LQPELDSFKEELDKYFKNHTSPDV. In some embodiments, a stem helix comprises a sequence having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications relative to LQPELDSFKEELDKYFKNHTSPDV.

[00695] In some embodiments, a stem helix peptide and a fusion peptide are directly linked to one another. In some embodiments, a stem helix peptide and a fusion peptide are connected via an endogenous sequence (i.e., a sequence that connects the stem helix peptide and fusion peptide regions in a native S protein). In some embodiments, a stem helix peptide and a fusion peptide are connected via a non-endogenous sequence (i.e., a sequence that does not connect a stem helix peptide and a fusion peptide in the native S protein). In some embodiments, a stem helix peptide and a fusion peptide are connected via a sequence that comprises a linker, including, e.g., a flexible linker. In some embodiments, the flelxible linker comprises one or more Gly residues and/or one of more Ser residues (e.g., a linker described in Table X of the present disclosure). In some embodiments, the flexible linker comprises 1-10, about 3, about 5, about 7 or about 10 Gly or Ser residues. [00696] In some embodiments, an S2 polypeptide comprises one or more mutations that can stabilize the structure of the S2 polypeptide (e.g., stabilize the prefusion confirmation of the S2 polypeptide). Examples of such mutations are described e.g., in Bowen, John E., et al. "SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines," Science Immunology 7.78 (2022): eadfl421; Hsieh, Ching-Lin, et al. "Structure-based design of prefusion-stabilized SARS-CoV-2 spikes," Science 369.6510 (2020): 1501-1505; Olmedillas, Eduardo, et al. "Structure-based design of a highly stable, covalently-linked SARS- CoV-2 spike trimer with improved structural properties and immunogenicity" bioRxiv (2021): 2021-05; Halfmann, Peter J., et al. "Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses," EBioMedicine 86 (2022); Nuqui, Xandra, et al. "Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens," bioRxiv (2023): 2023-10; and Low, Jun Siong, et al. "ACE2- binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies," Science 377.6607 (2022): 735-742;, each of which is incorporated by reference herein in its entirety. In some embodiments, [00697] In some embodiments, a coronavirus S2 polypeptide (e.g., a SARS-CoV-2 S2 polypeptide) comprises substitutions corresponding to those shown to stabilize other coronavirus S2 polypeptides (e.g., other betacoronavirus S2 polypeptides, other sarbecovirus S2 polypeptides, MERS S2 polypeptide, and/or SARS-CoV-1 S2 polypeptides). E.g., in some embodiments, a SARS-CoV-2 S2 polypeptide described herein comprises one or more mutations at positions corresponding to one or more of the mutations described in Hsieh, Ching-Lin, et al. "Stabilized coronavirus spike stem elicits a broadly protective antibody" Cell reports 37.5 (2021), which describes mutations shown to stabilize a MERS S2 polypeptide, and the contents of which are incorporated by reference herein in their entirety. In some embodiments, a SARS-CoV-2 S2 polypeptide comprises one or more mutations corresponding to S375C, T859C, Q901M, A1020Q, H1058Y, or combinations thereof (mutations shown relative to SEQ ID NO: 1). In some embodiments a SARS-CoV-2 S polypeptide comprises mutations corresponding to S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L826C, L948C, or combinations thereof. In some embodiments, a SARS-CoV-2 S2 polypeptide comprises one or both pairs of mutations corresponding to I770C and A1015C, and/or V826C and L948C (mutations shown relative to SEQ ID NO: 1). In some embodiments, an S2 polypeptide comprises a sequence corresponding to that of constructs 21 and 22 listed in the below Table I.

[00698] In some embodiments, an S2 polypeptide comprises one or more of the following mutations relative to SEQ ID NO: 1, or corresponding mutation(s) in an S2 polypeptide of an S protein of a SARS-CoV-2 variant:

(a) K986P and V987P;

(b) A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P;

(c) F817P, A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P; or

(d) any combination of (a)-(c).

[00699] In some embodiments, an S2 polypeptide comprises one or more mutations that can result in the formation of a disulfide bond. In some embodiments, an S2 polypeptide comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S2 polypeptide of a SARS-CoV-2 variant:

(a) V707C and T883C; (b) I770C and A1015C;

(c) V826C and A1015C;

(d) V826C and L948C;

(e) F970C and G999C;

(f) S735C and T859C; or

(g) any combination of (a)-(f).

[00700] In some embodiments, an S2 polypeptide comprises one or more of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S protein of a SARS-CoV-2 variant:

(a) V707C, T883C, F970C, and G999C;

(b) S735C, T859C, I770C, and A1015C;

(c) S735C, T859C, V826C, and L948C;

(d) I770C, A1015C, V826C, and L948C;

(e) S735C, I770C, A1015C, V826C, and L948C; or

(f) any combination of (a)-(e).

[00701] In some embodiments, an S2 polypeptide comprises one or more Pro substitions and one or more mutations that can result in the formation of a disulfide bond.

[00702] In some embodiments, an S2 polypeptide comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresonding combination of mutations of an S2 polypeptide of a SARS-CoV-2 variant:

(a) A892P, A899P, 941, K986P, V987P, G999C, and I770C;

(b) A892P, A899P, A942P, V987P, V707C, T883C, optionally wherein the S2 polypeptide compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(c) A892P, A899P, A942P, V987P, V707C, T883C, F970C, G999C, optionally wherein the S2 polypeptide compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1. [00703] In some embodiments, an S2 polypeptide comprises one or more mutations that can prevent or reduce cleavage at the S2' cleavage site. In some embodiments, an S2 polypeptide comprises one or more mutations that remove a S2' protease cleavage site. In some embodiments, an S2 polypeptide comprises one or more mutations at positions corresponding to amino acids 814 and/or 815 of SEQ ID NO: 1, optionally wherein the one or more mutations are a Gly, Ser, or Ala substition (e.g., a Gly substition). In some embodiments, an S2 polypeptide comprises Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1. [00704] In some embodiments, an S2 polypeptide comprises one or more Pro substitutions that can stabilize the S2 domain and one or more mutations that disrupt a S2' protease cleavage site.

[00705] In some embodiments, an S2 polypeptide comprises one or more of the following mutations relative to SEQ ID NO: 1: A892P, A899P, A942P, K986P, V987P, or any combination thereof, or corresponding mutations in a SARS-Cov-2 variant, and a Gly substituion at positions 814 and/or 815 of SEQ ID NO: 1.

[00706] In some embodiments, an S2 polypeptide comprises one or more substitutions of a hydrophillic amino acid for a hydrophobic amino acid, wherein the one or more hydrophobic amino acids are at positions that are solvent explosed in the S2 polypeptide.

[00707] In some embodiments, an S2 polypeptide comprises a substitution of a hydrophillic amino acid at one or more positions corresponding to amino acid 855, 861, 864, 976, or 984 of SEQ ID NO: 1, or any combination thereof. [00708] In some embodiments, an S2 polypeptide comprises one or more of the following mutations relative to SEQ ID NO: 1 F855S, L861E, L864D, V976D, and L984Q, or any combination thereof, or corresponding mutations in an S2 polypeptide of a SARS-CoV-2 variant.

[00709] In some embodiments, an S2 polypeptide comprises an amino acid substitution at one or more of the amino acids at positions 901, 1020, 1058, or any combination thereof relative to SEQ ID NO: 1, or corresponding substitutions in an S2 polypeptide of a SARS-CoV-2 variant.

[00710] In some embodiments, a construct comprises one or more of the following mutations relative to SEQ ID NO: 1: Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S2 polypeptide of a SARS-CoV-2 variant.

[00711] In some embodiments, an S2 polypeptide comprises:

(a) one or more of the following mutations: S375C, T859C, Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1, Pro substitutions at positions corresponding to amino acids K986P and/or V987P of SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(b) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, and Pro substiutions at positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1, wherein mutations are shown relative to SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(c) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1; or

(d) any combination of (a)-(c).

[00712] In some embodiments, an S2 domain comprises one or more subsitions of a hydrophobic residue for a hydrophillic residue at one or more positions that are solvent buried in the context of the full length S protein, but which are solvent exposed in the absense of the SI domain. In some embodiments, the one or more hydrophic residues include F855S, L861E, L864D, V976D, and L984Q, where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 polypeptide of a SARS-CoV-2 variant. In some embodiments, an S2 polypeptide comprises one or more of the following mutations: L861E, L864D, V976D, and L984Q, a Pro substitution at one or more positions corresponding to amino acids F817P, A892P, A899P, A942P, or combinations thereof of SEQ ID NO: 1, optionally in combination with a Pro substitution at one or both positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1; or where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 polypeptide of a SARS-CoV-2 variant.

[00713] In some embodiments, an RNA described herein comprises a nucleotide sequence that encodes a polypeptide comprising an immunogenic fragment of an S2 polypeptide. In some embodiments, an RNA encodes a polypeptide comprising an immunogenic fragment of an S2 polyeptide described in Zhou, Panpan, et al.

"Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease." Immunity 56.3 (2023): 669-686, the contents of which are incorporated by reference herein in their entirety. In some embodiments, an immunogenic fragment of the S2 polypeptide comprises the fusion peptide of an S2 polypeptide (e.g., PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD) and/or the stem helix of an S2 polypeptide (e.g., LQPELDSFKEELDKYFKNHTSPDV), which have previously been shown to be capable of inducing a broad and potent antibody response that is difficult for a coronavirus to escape. In some embodiments, an immunogenic fragment of an S2 polypeptide comprises the stem-helix of an S2 polypeptide and the fusion peptide of an S2 polypeptide, optionally connected via a flexible linker (e.g., a flexible linker described herein). In some embodiments, a polypeptide comprising a stem-helix and/or a fusion peptide of S2 can be membrane- tethered (e.g., by attaching a transmembrane domain described herein (e.g., C-terminal to the stem-helix and/or fusion peptide)). In some embodiments, a polypeptide comprising a stem-helix and/or of a fusion peptide of an S2 polypeptide can be secreted (e.g., by inclusion of a secretion signal (e.g., a secretion signal described herein, optionally position at the N-terminus of the polypeptide) and omission of a transmembrane domain). One example of an S2 stem helix fused to an S2 fusion peptide is a polypeptide comprising the following sequence: PSKPSKRSFIEDLLFNKVFLADAGFIKQYGDCLGDGSGLQPELDSFKEELDKYFKNHTSPDV.

[00714] In some embodiments, a fusion peptide comprises a sequence of PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto, and the stem helix comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

S2-RBD Fusions

[00715] In some embodiments, a polypeptide comprising an S2 domain or one or more immunogenic fragments thereof, also comprises an RBD polypeptide.

[00716] In some embodiments, an RBD and an S2 domain or one or more immunogenic fragments of an S2 domain are connected via a non-endogenous sequence. As used herein, the term "non-endogenous sequence," when used in reference to a sequence (e.g., an amino acid sequence) that connects two domains, regions, or fragments of the same protein (e.g., an RBD and an S2 domain of a coronavirus S protein), refers to a sequence (e.g., an amino acid sequence) that does not connect the two domains, regions, or fragments in a native, full- length protein. For example, in some embodiments, a non-endogenous sequence used to connect an RBD of an S protein to an S2 domain of an S protein (or one or more immunogenic fragments of an S2 domain) in a polypeptide described herein is an amino acid sequence that is not naturally occurring in an S protein (e.g., a wild-type S protein). In some embodiments, the non-endogenous sequence is an amino acid sequence containing one or more mutations (including one or more deletions, insertions, and/or substitutions) relative to a naturally occurring sequence belonging to an S protein (e.g., a naturally occurring sequence between an RBD and an S2 domain of a wild-type S protein). In some embodiments, a non-endogenous linker comprises a deletion of a naturally occurring sequence between two fragments in a native, full-length protein (e.g,. for polypeptides comprising an RBD and an S2 domain, a deletion of a portion or the entirety of a sequence between the RBD and the S2 domain in a native, full-length S protein). In some embodiments, a non-endogenous sequence comprises one or more deletions relative to the endogenous sequence (e.g., endogenous sequence of a native, full-length protein). In some embodiments, a polypeptide comprising an S2 domain or one or more fragments thereof and an RBD lacks one or more other regions of a coronavirus S protein (e.g., one or more other regions of an S protein that naturally occur between an S2 domain and an RBD). In some embodiments, a polypeptide comprising an S2 domain or one or more fragments thereof and an RBD lacks an NTD and/or other regions that naturally occur between an RBD and an S2 domain of an S protein. In some embodiments, an RBD and an S2 domain or one or more fragments of an S2 domain are directly attached to one another (i.e., without an intervening linker sequence). In some embodiments, an RBD and an S2 domain or one or more fragments of an S2 domain are connected via a non-endogenous sequence that comprises a linker sequence (e.g., as described herein).

[00717] In some embodiments, an S2 polypeptide (comprising an S2 domain), or immunogenic fragment thereof, is connected to an RBD polypeptide (comprising an RBD) via a non-endogenous sequence that comprises a flexible linker (e.g., a flexible linker as described herein). In some embodiments, the flexible linker comprises a protease cleavage site, such that the S2 polypeptide and the RBD polypeptide can be cleaved as they are transported to the cell surface and/or once they reach the cell surface. In some embodiments, the flexible linker comprises a protease recognition site for a protease that is active at the cell surface and/or that is active at one or more steps in transporting a polypeptide to the cell surface. Suitable protease cleavage sites, include, e.g., a furin cleavage site. One example of a linker sequence comprising a furin cleavage site is a polypeptide comprising the following sequence: AGNRVRRSVG, or a variant thereof which can still be cleaved by a furin protease (e.g., human furin protease). In some embodiments, a flexible linker comprises a GS linker (e.g., wherein the GS linker 5, 10, 15, or 20 amino acids in length). In some embodiments, a GS linker comprises a sequence of (G4S)1, (G4S)2, (G4S)3, or (G4S)4. In some embodiments, a GS linker is about 5 to about 20 amino acids in length, including, e.g., about 5, about 10, about 15, or 20 amino acids in length.

[00718] In some embodiments, an RBD and an S2 domain or one or more fragments thereof are directly adjacent to one another. In embodiments, where an RBD and an S2 domain are directly adjacent to one another, no intervening sequence connects the two domains (i.e., the junction of the two domains only comprises RBD and S2 domain sequence). Provided below is one example of a polypeptide in which an S2 domain (comprising amino acids 611-1211 of SEQ ID NO: 1) is directly adjacent to an RBD (amino acids 327 to 528 of SEQ ID NO: 1): [00719] VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQL NRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLI CAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQ DSLSSTASALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRAS ANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFV TQRNFYEPQIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVA KNLNESLIDLQELGKYEQYIKVRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNFAPFFAFKCYGVSPTKLNDLCF TNVYADSFVIRGNEVSQIAPGQTGNIADYNYKLPDDFTGCVIAWNSNKLDSKPSGNYNYLYRLFRKSKLKPFERDISTEIYQAGN KPCNGVAGPNCYSPLQSYGFRPTYGVGHQPYRVWLSFELLHAPATVCGPK

[00720] In some embodiments, an S2 polypeptide (comprising an S2 domain), or immunogenic fragment thereof, is attached to an RBD polypeptide (comprising an RBD) via a flexible linker (e.g., a flexible linker as described herein). In some embodiments, the flexible linker comprises a protease cleavage site, so that the S2 polypeptide and the RBD polypeptide can be cleaved as they are transported to the cell surface and/or once they reach the cell surface. In some embodiments, the flexible linker comprises a protease recognition site for a protease that is active at the cell surface and/or that is active at one or more steps in transporting a polypeptide to the cell surface. Suitable protease cleavage sites, include, e.g., a furin cleavage site. One example of a linker sequence comprising a furin cleavage site is a polypeptide comprising the following sequence: AGNRVRRSVG, or a variant thereof which can still be cleaved by a furin protease (e.g., human furin protease).

[00721] In some embodiments, an S2 polypeptide and an RBD are connected via a non-endogenous sequence that comprises a rigid linker (e.g., a polypeptide comprising PA repeating, to a total length of 25-30 amino acids). In some embodiments an S2 polypeptide and an RBD are connected via a non-endogenous sequence that comprises a helical linker (e.g., a polypeptide comprising one of the following sequences: AEAAAKEAAAKA, AEAAAKEAAAKEAAAKA, AEAAAKEAAAKEAAAKEAAAKA, or AEAAAKEAAAKEAAAKEAAAKEAAAKA). [00722] In some embodiments, a polypeptide comprises an RBD and one or more immunogenic fragments of an S2 polypeptide (e.g., a stem helix and a fusion peptide of an S2 polypeptide (e.g., as described herein)). [00723] The stem helix region of an S protein is located within the S2 domain. In some embodiments, an SH region comprises the amino acids between about residue 1139 of SEQ ID NO: 1 (e.g., residue 1134, 1135, 1136, 1137, 1128, 1129, 1140, 1141, 1142, or 1143 of SEQ ID NO: 1) to and about residue 1163 of SEQ ID NO: 1 (e.g., residue 1158, 1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, or 1168 of SEQ ID NO: 1), or a corresponding region of a SARS-CoV-2 S protein. In some embodiments, an SH region comprises the amino acid sequence between residue 1139 and residue 1163 of SEQ ID NO: 1, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 variant.

[00724] The stem helix region of an S protein is located within the S2 domain. In some embodiments, an SH region comprises the amino acids between about residue 1141 of SEQ ID NO: 1 (e.g., residue 1136, 1137, 1128, 1129, 1140, 1141, 1142, 1143, 1144, 1146 of SEQ ID NO: 1) to and about residue 1160 of SEQ ID NO: 1 (e.g., residue 1155, 1156, 1157, 1158, 1159, 1160, 1161, 1162, 1163, 1164, or 1165 of SEQ ID NO: 1), or a corresponding region of a SARS-CoV-2 S protein. In some embodiments, an SH region comprises amino acids 1141-1160 of SEQ ID NO: 1, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 variant. [00725] The stem helix region of an S protein is located within the S2 domain. In some embodiments, an SH region comprises the amino acids between about residue 1141 of SEQ ID NO: 1 (e.g., residue 1136, 1137, 1128, 1129, 1140, 1141, 1142, 1143, 1144, 1146 of SEQ ID NO: 1) to and about residue 1164 of SEQ ID NO: 1 (e.g., residue 1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, 1168, or 1169 of SEQ ID NO: 1), or a corresponding region of a SARS-CoV-2 S protein. In some embodiments, an SH region comprises amino acids 1141-1164 of SEQ ID NO: 1, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 variant. [00726] The stem helix region undergoes a conformational change when an S protein transitions from a prefusion state to a postfusion state, during which the stem helix region becomes an extended six-helix bondle. Because the structural prefusion to postfusion structural transition of an S protein is an important step in virushost membrane fusion, it is expected that antibodies targeting the S2 stem helix region may be able to block SARS-CoV-2 infection. Indeed, the SH region has been shown to comprise neutralizing eptiopes. See, e.g., Li, Chia-Jung, and Shih-Chung Chang. "SARS-CoV-2 spike S2-specific neutralizing antibodies." Emerging Microbes & Infections 12.2 (2023): 2220582. Moreover, the SH region is also highly conserved among SARS-CoV-2 variants. Unfortunately, B cells and antibodies that bind the SH region are rarely induced by vaccines that deliver a full length S protein or by SARS-CoV-2 infection. Thus, a vaccine that can more consistently induce an immune response against the SH region coule provide significant adavantages as compared to alternative vaccines (e.g., vaccines that deliver an S2 domain), e.g., by inducing an immune response characterized by higher neutralizing titers and/or by inducing a more broadly cross-neutralizing immune response.

[00727] The fusion peptide is in the S2 domain and is well characterized structurally. See, e.g., Shi, Wei, et al. "Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane." Nature 619.7969 (2023): 403-409, the contents of which are incorporated by reference herein in its entirety. In the native S protein, the fusion peptide can insert into a target cell membrane. To infect a new cell, the S protein binds ACE2 on the cell surface, at which point it is cleaved at the S2' site by the host serine protease TMRSS2 or the endosomal systein protease cathepsin. Following cleavage, the S prteoin underoes large conformation changes to isnert the FP into the target cell membrane and then refold into a hairpin like postfusion structure, placing the transmebrnae segment and fusion peptide at the same end of the moledule, dragging the two membranes together to complete fusion. [00728] In some embodiments an FP comprises the amino acid sequence of about residue 809 of SEQ ID NO: 1 (e.g., residue 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814 of SEQ ID NO: 1) to about residue 843 of SEQ ID NO: 1 (e.g., residue 838, 839, 840, 841, 842, 843, 944, 945, 846, 847, or 848 of SEQ ID NO: 1), or a corresponding region of an S protein of a SARS-CoV-2 variant.

[00729] In some embodiments, an FP comprises the amino acid sequence between about residue 816 of SEQ ID NO: 1 (e.g., residue 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, or 821 of SEQ ID NO: 1) and abour residue 834 of SEQ ID NO: 1 (e.g., residue, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, or 839 of SEQ ID NO: 1). In some embiments an FP comprises amino acids 816-834 of SEQ ID NO: 1 or a corresponding region of an S protein of a SARS-CoV-2 variant. In some embodiments, an FP comprises amino acids 809-843 of SEQ ID NO: 1, or a corresponding region of an S protein of a SARS-CoV-2 variant.

[00730] Similar to the SH region, the FP is highly conserved in SARS-CoV-2, and also comprises neutralizing epitopes. Thus, a vaccine that can more consistently induce an FP immune response (e.g., as compared to a composition that administers a full length S protein) would potentially offer significant advantages, including, e.g., higher titers of neutralizing antibodies, and/or a more broadly cross neutralizing immune response.

[00731] In some embodiments, a polypeptide comprising an S2 polypeptide (or one or more immunogenic fragments and/or variants thereof), and optionally an RBD polypeptide, comprises a transmembrane domain (e.g., an endogenous or exogenous transmembrane domain). Suitable transmembrane domains include, e.g., transmembrane domains described herein.

[00732] In some embodiments, a polypeptide comprising an S2 polypeptide (or an immogenic fragment and/or variant thereof) also comprises a trimerization domain. In some embodiments, a polypeptide comprising an S2 polypeptide, an RBD, and a protease cleavage site comprises two trimerization domains, which are configured such that, after cleavage of the protease cleavage site, a trimerization domain is present in the polypeptide comprising the S2 polypeptide and the polypeptide comprising the RBD.

[00733] In some embodiments, an S2 domain is N-terminal or C-terminal to the RBD.

[00734] In some embodiments, a polypeptide comprising an RBD and an S2 domain does not comprise an

NTD.

[00735] In some embodiments, an RBD is directly linked to an S2 polypeptide.

[00736] In some embodiments, an RBD is connected to an S2 polypeptide via a linker sequence. In some embodiments, a linker sequence is a flexible linker sequence, a helical linker sequence, or a rigid linker sequence. In some embodiments, a linker sequence comprises a protease recognition site. In some embodiments, a linker sequence comprises a furin recognition site (e.g., an amino acid sequence of AGNRVRRSVG, or an amino acid with 1, 2, 3, 4, or more mutations thereto).

[00737] In some embodiments, a polypeptide comprising an S2 domain and an RBD also comprises a multimerization domain (e.g., where a fibritin domain is attached to each of the S2 polyeptpide and the RBD, and the RBD and the S2 polypeptide are connected via a linker that comprises a protease cleavage site, and the polypeptide is configured such that, upon cleavage of the furin cleavage site, a fibritin domain is attached to each of the S2 polypeptide and the RBD. In some embodiments, a polypeptide is configured such that the RBD is membrane bound and the S2 domain is soluble.

[00738] In some embodiments, the present disclosure describes an RNA encoding a polypeptide comprising an RBD and a stem helix and fusion peptide regions of an S2 domain. In some embodiments, the stem helix and the fusion peptide are connected via a non-endogenous peptide sequence. In some embodiments, the stem helix and the fusion peptide are directly linked to one another and/or wherein the stem helix and the fusion peptide are connected via a sequence that comprises a flexible linker. In some embodiments, an RBD is connected to the stem helix and/or the fusion peptide via a non-endogenous sequence. In some embodiments, an RBD is directly linked to the stem helix and/or the fusion peptide. In some embodiments, an RBD is linked to the stem helix and/or the fusion peptide via a flexible linker. In some embodiments, an RBD is N-terminal to the stem helix and the fusion peptide. In some embodiments, an RBD is C-Terminal to the stem helix and the fusion peptide. In some embodiments, the N-terminal to C-terminal order of the RBD, stem helix, and fusion peptide is: (RBD)- (stem helix)-(fusion peptide), or (stem helix)-(fusion peptide)-(RBD), optionally wherein there is one or more linkers (e.g., a flexible linker) and/or domains (e.g., transmembrane domain or multimerization domains) between one or more of the RBD, stem helix, and fusion peptide. In some embodiments, the stem helix and the fusion peptide are directly linked to one another, and wherein the RBD is N-terminal or C-terminal to the stem helixfusion peptide region.

[00739] In some embodiments, a polypeptide comprising an RBD and an S2 domain, or an SH and FP region of the S2 domain also comprises a transmemrbrane domain. In such embodiments, the N-terminal to C-terminal orientation of the polypeptide can be: (a) (transmembrane domain)-(stem helix)-(fusion peptide)-(RBD); or (b) (transmembrane domain)-(RBD)-(stem helix)-(fusion peptide).

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA (SEQ ID NO: 470)

S2 construct design - secreted S2 M FVFLVLLPLVSSQCVN LTVASQSIIAYTM SLGAEN SVAYSN N SIAIPTN FTIS\nTEI LPVSMTKTSVDCTMYICG DSTECSNLLLQYGSFCTQL

2P + membrane-bound RBD NRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL

Secretory Signals

[00740] In some embodiments, an antigen construct described herein includes a secretory signal, e.g., that is functional in mammalian cells. In some embodiments, a utilized secretory signal is a heterologous secretory signal. As used herein, a heterologous secretory signal refers to a secretory signal is from a different organism than one or more antigens that is in the same polypeptide sequence. For example, for a polypeptide comprising one or more SARS-CoV-2 S protein antigens, a heterologous secretory signal is a non-SARS-CoV-2 secretory signal.

[00741] In some embodiments, a utilized secretory signal is a homologous secretory signal (i.e., a secretory signal that is naturally found in the same protein as an encoded antigen, including e.g., the N-terminal 16 or 19 amino acids of a SARS-CoV-2 S protein when attached to an antigen of a SARS-CoV-2 S protein).

[00742] In some embodiments, a heterologous secretory signal comprises or consists of a non-human secretory signal. In some embodiments, a heterologous secretory signal comprises or consists of a viral secretory signal. In some embodiments, a viral secretory signal comprises or consists of an HSV secretory signal (e.g., an HSV-1 or HSV-2 secretory signal). As used, herein, reference to a "secretory signal" in the context of a polypeptide, is synonymous with a "secretory signal peptide."

[00743] In some embodiments, a secretory signal comprises or consists of an Ebola virus secretory signal. In some embodiments, an Ebola virus secretory signal comprises or consists of an Ebola virus spike glycoprotein (SGP) secretory signal.

[00744] In some embodiments, a secretory signal is characterized by a length of about 15 to 30 amino acids.

[00745] In many embodiments, a secretory signal is positioned at the N-terminus of a SARS-CoV-2 antigen construct as described herein. In some embodiments, a secretory signal preferably allows transport of the SARS- CoV-2 antigen construct with which it is associated into a defined cellular compartment, preferably a cell surface, endoplasmic reticulum (ER) or endosomal-lysosomal compartment.

[00746] In some embodiments, a secretory signal is selected from an S1S2 signal peptide (e.g., aa 1-16 or 1-19), an immunoglobulin secretory signal (e.g., aa 1-22), an HSV-1 gD signal peptide (MGGAAARLGAVILFWIVGLHGVRSKY; SEQ ID NO: 7), an HSV-2 gD signal peptide (MGRLTSGVGTAALLWAVGLRWCA; SEQ ID NO: 8); a human SPARC signal peptide, a human insulin isoform 1 signal, a human albumin signal peptide, etc. Those skilled in the art will be aware of other secretory signal such as, for example, as disclosed in W02017/081082, which is incorporated herein by reference in its entirety (e.g., SEQ ID NOs: 1-1115 and 1728, or fragments variants thereof).

[00747] In some embodiments, a SARS-CoV-2 antigen construct described herein does not comprise a secretory signal.

[00748] In certain embodiments, a signal peptide is an IgG signal peptide, such as an IgG kappa signal peptide.

[00749] In some embodiments, a SARS-CoV-2 secretory signal comprises or consists of an HSV glycoprotein D (gD) secretory signal.

[00750] In one embodiment, a signal sequence comprises the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31, or a functional fragment of the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31. In one embodiment, a signal sequence comprises the amino acid sequence of amino acids 1 to 22 of SEQ

ID NO: 31.

[00751] In one embodiment, RNA encoding a signal sequence (i) comprises the nucleotide sequence of nucleotides 54 to 119 of SEQ ID NO: 32, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 54 to 119 of SEQ ID NO: 32, or a fragment of the nucleotide sequence of nucleotides 54 to 119 of SEQ ID NO: 32, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 54 to 119 of SEQ ID NO: 32; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31, or a functional fragment of the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31. In one embodiment, RNA encoding a signal sequence (i) comprises the nucleotide sequence of nucleotides 54 to 119 of SEQ ID NO: 32; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31.

[00752] Such signal peptides are preferably used in order to promote secretion of the encoded antigenic peptide or protein. More preferably, a signal peptide as defined herein is fused to an encoded antigenic peptide or protein as defined herein.

[00753] Accordingly, in particularly preferred embodiments, the RNA described herein comprises at least one coding region encoding an antigenic peptide or protein and a signal peptide, said signal peptide preferably being fused to the antigenic peptide or protein, more preferably to the N-terminus of the antigenic peptide or protein as described herein.

[00754] In some embodiments, a string construct sequence encodes an antigen that may comprise or otherwise be linked to a signal sequence {e.g., secretory signal), such as those listed in Table 2 or at least a sequence having 1, 2, 3, 4, or 5 amino acid differences relative thereto. In some embodiments, a secretory signal such as MFVFLVLLPLVSSQCVNLT (SEQ ID NO: 9), or at least a sequence having 1, 2, 3, 4, or at the most 5 amino acid differences relative thereto is utilized.

[00755] In some embodiments, a secretory signal is selected from a gl signal peptide. In some embodiments, a secretory signal such as MPGRSLQGLAILGLWVCATGLWR (SEQ ID NO: 10), or at least a sequence having 1, 2, 3, 4, or at the most 5 amino acid differences relative thereto is utilized. In some embodiments, a secretory signal such as MPGRSLQGLAILGLWVCATGL (SEQ ID NO: 11), or at least a sequence having 1, 2, 3, 4, or at the most 5 amino acid differences relative thereto is utilized.

[00756] In some embodiments, an antigen comprises an affinity label (e.g., a short sequence that can bind to an affinity reagent, and which can be useful for, e.g., affinity purification of a protein). Suitable affinity labels are known in the art, and include e.g., a His tag (e.g., HHHHHHHH) and a StrepTag® (e.g., WSHPQFEK). In some embodiments, an affinity label can be included at the N-terminus of an antigen (e.g., adjacent to a secretory signal (to which it is optionally connected via a fleixible linker)).

[00757] In some embodiments, a secretory signal is one listed in Table 2 and/or Table 3, or a secretory signal having 1, 2, 3, 4, or 5 amino acid differences relative thereto. In some embodiments, a secretory signal is selected from those included in the Table 2 below and/or those encoded by the sequences in Table 3 below. [00758] In some embodiments, an mRNA construct encodes a polypeptide comprising amino acids 20 to 292 of SEQ ID NO: 145 (or variants thereof) and a secretory signal from Table 2. Table 2: Exemplary secretory signals

Table 3: Exemplary polynucleotide sequences encoding secretory signals

Multi merization Domains

[00759] In some embodiments, an RNA utilized as described herein encodes a multimerization element (e.g., a heterologous multimerization element). In some embodiments, a heterologous multimerization element comprises a dimerization, trimerization or tetramerization element.

[00760] In some embodiments, a multimerization element is one described in W02017/081082 (e.g., SEQ ID NOs: 1116-1167, or fragments or variants thereof).

[00761] Exemplary trimerization and tetramerization elements include, but are not limited to, engineered leucine zippers, fibritin foldon domain from enterobacteria phage T4, GCN4pll, GCN4-pll, and p53.

[00762] In some embodiments, a provided encoded polypeptide(s) is able to form a trimeric complex. For example, a utilized encoded polypeptide(s) may comprise a domain allowing formation of a multimeric complex, such as for example particular a trimeric complex of an amino acid sequence comprising an encoded polypeptide(s) as described herein. In some embodiments, a domain allowing formation of a multimeric complex comprises a trimerization domain, for example, a trimerization domain as described herein.

[00763] In some embodiments, an encoded polypeptide(s) can be modified by addition of a T4-fi britin- derived "foldon" trimerization domain, for example, to increase its immunogenicity.

[00764] In some embodiments, a heterologous multimerization region comprises a dimerization, trimerization or tetramerization region.

[00765] In some embodiments, a multimerization region is one described in W02017/081082, which is incorporated herein by reference in its entirety (e.g., SEQ ID NOs: 1116-1167, or fragments or variants thereof). Exemplary trimerization and tetramerization regions include, but are not limited to, engineered leucine zippers, fibritin domain from enterobacteria phage T4, GCN4pll, GCN4-pll, and p53.

[00766] In some embodiments, a provided SARS-CoV-2 construct described herein is able to form a trimeric complex. For example, a provided SARS-CoV-2 construct may comprise a multimerization region allowing formation of a multimeric complex, such as for example a trimeric complex of a SARS-CoV-2 construct described herein. In some embodiments, a multimerization region allowing formation of a multimeric complex comprises a trimerization region, for example, a trimerization region described herein. In some embodiments, a SARS-CoV-2 construct includes a T4-fibritin-derived "foldon" trimerization region, for example, to increase its immunogenicity. In some embodiments, a SARS-CoV-2 construct includes a multimerization region comprising or consisting of the amino acid sequence GYIPEAPRDGQAYVRKDGEWVLLSTFL (SEQ ID NO: 95). In some embodiments, a SARS-CoV- 2 construct includes a multimerization region comprising or consisting of the amino acid sequence GYIPEAPRDGQAYVRKDGEWVLLSTFLGRSLEVLFQGPG (SEQ ID NO: 96). An exemplary nucleotide sequences encoding SEQ ID NO: 96 is GGCUAUAUCCCUGAGGCUCCUAGAGAUGGCCAGGCCUACGUCAGAAAGGAUGGCGAGUGGGUCCUGCUGAGCACCUUUC UGGGCAGAUCCCUGGAAGUGCUGUUUCAAGGCCCUGGC (SEQ ID NO: 97). An exemplary nucleotide sequence encoding SEQ ID NO: 95 is GGCTATATCCCTGAGGCTCCTAGAGATGGCCAGGCCTACGTCAGAAAGGATGGCGAGTGGGTCCTGCTGAGCACCTTTCTG (SEQ ID NO: 98).

[00767] In some embodiments, a multimerization domain is a soluble multimerization domain (i.e., not a transmembrane domain). In some embodiments, a transmembrane domain is capable of inducing multimerization (e.g., trimerization), and thus, can also be considered a multimerization domain. In some embodiments, a polypeptide described herein comprises a transmembrane domain that is capable of inducing multimerization (e.g., trimerization), and lacks a soluble trimerization domain. In some embodiments, a polypeptide described herein comprises a transmembrane domain that is capable of inducing multimerization and also comprises a soluble trimerization domain. Inclusion of a multimerization domain can provide certain immunogenic fragments as compared to the same polypeptide lacking a multimerization domain. Such advantages include, e.g., increased structural stability of an antigen, an antigen with a structure that more closely matches the structure of an endogenous antigen, and/or improved induction of an immune response.

[00768] Among other things, the present disclosure provides approaches for producing higher order oligomers (e.g., oligomers comprising more than 3 SARS-CoV-2 antigens). In some embodiments, polypeptides described in here can induce highly multimeric oligomers (e.g., oligomers approximately 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, or 60 or more SARS-CoV-2 antigens), generate an improved immune response (e.g., as compared to a composition comprising the same amount of RNA (in terms of mass or moles)) encoding a polypeptide producing a monomer or an oligomer comprising fewer SARS-CoV-2 antigens), and/or can display antigenic polypeptides in a confirmation that is preferred for generating an immune response. [00769] In some embodiments, an RNA can encode a polypeptide comprise two or more antigenic regions (e.g., two or more RBDs, three or more RBDs, four or more RBDs, or five or more RBDs), e.g., as described in Gao et al., the contents of which are incorporated by reference herein in their entirety.

[00770] In some embodiments, an RNA can encode two or more antigenic regions (e.g., can encode a polypeptide comprising two or more RBD polypeptides), and further comprise a multimerization domain (e.g., a T4 fibritin domain). For example, in some embodiments, a polypeptide provides two or more (e.g., 2, 3, or 4) antigen regions (e.g., RBD polypeptides) and a multimerization (e.g., trimerization) domain. In some embodiments, a polypeptide provided herein comprises two RBD polypeptides and a trimerization domain, such that an oligomer comprising six RBD polypeptides (a "trimer of dimers", where each "dimer" refers to a polypeptide comprising two RBD polypeptides) can be formed.

[00771] In some embodiments, a multimerization can induce highly multivalent oligomers (e.g., oligomers comprising 10 or more antigenic polypeptides).

[00772] In some embodiments, a multimerization domain can induce multimerization of 10, 15, 20, 24, 25, 30, 35, 40, 45, 50, 55, 60, or more antigenic polypeptides.

[00773] In some embodiments, multimerization domains are selected so as to reduce an immune response generated against the multimerization domain itself. For example, in some embodiments, a relatively small multimerization domain is used (e.g., a multimerization domain comprising about 100 amino acids or less and/or a multimerization domain that comprises less than 20% of the total amino acids in a polypeptide). Additionally or alternatively, in some embodiments, a multimerization domain is used that forms an oligomer structure in which (i) the multimerization domain is not freely accessible in solution, and/or has reduced solvent accessibility as compared to a relevant comparator (e.g., other multimerization domains commonly used in commercial vaccines, e.g., a T4 fibritin domain); and/or (ii) the majority of antigen is freely accessible in solution and/or forms the majority of the solvent exposed surface area of an oligomer (e.g., 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, or 80% or more).

[00774] Suitable multimerization domains include, e.g., those described in, Lainscek, Dusko, et al. "A nanoscaffolded spike-RBD vaccine provides protection against SARS-CoV-2 with minimal anti-scaffold response," Vaccines 9.5 (2021): 431; Joyce, M. Gordon, et al. "SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity," Cell reports 37.12 (2021); Joyce, M. Gordon, et al. "A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates," Science translational medicine 14.632 (2021): eabi5735; Wang, Chong, et al. "Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice." Antiviral research 140 (2017): 55-61; Johnston, Sara C., et al. "A SARS-CoV-2 spike ferritin nanoparticle vaccine is protective and promotes a strong immunological response in the cynomolgus macaque coronavirus disease 2019 (COVID-19) model," Vaccines 10.5 (2022): 717; Zhang, Baoshan, et al. "A platform incorporating trimeric antigens into selfassembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone," Scientific reports 10.1 (2020): 18149; Malhi, Harman, et al. "Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge." Cell Reports Medicine 3.6 (2022); and WO2022043449A1, the contents of each of which is incorporated by reference herein in their entirety.

[00775] In some embodiments, an mRNA construct described herein comprises a multimerization domain listed in Table 14.

[00776] Table 14: Exemplary Multimerization Domains

[00777] In some embodiments, a multimerization domain comprises a ferritin domain (e.g., as described in Table II). In some embodiments a multimerization domain comprises a ferritin domain that has been modified to reduced autoimmunity (e.g., as described in Kanekiyo, Masaru, et al. "Rational design of an Epstein-Barr virus vaccine targeting the receptor-binding site," Cell 162.5 (2015): 1090-1100, the contents of which are incorporated by reference herein in their entirety).

Transmembrane Domains

[00778] In some embodiments, an RNA described herein encodes a membrane association element (e.g., a heterologous membrane association element), such as a transmembrane domain.

[00779] In some embodiments, an RNA described herein encodes a polypeptide comprising a transmembrane domain, wherein the transmembrane domain is not a SARS-CoV-2 S protein transmembrane domain.

[00780] In some embodiments, a utilized transmembrane domain is a heterologous transmembrane domain. As used herein, a "heterologous transmembrane domain" when used to describe a polypeptide comprising an antigenic region, is heterologous relative to the antigenic region. For example, for a polypeptide comprising a SARS-CoV-2 antigen and a heterologous transmembrane domain, the heterologous transmembrane domain would be from a non-SARS-CoV-2 protein. In some embodiments, a heterologous transmembrane domain comprises or consists of a non-human transmembrane domain. In some embodiments, a heterologous transmembrane domain comprises or consists of a viral transmembrane domain.

[00781] In some embodiments, a utilized transmembrane domain is a homologous transmembrane domain (i.e., a transmembrane domain that is naturally found in the same protein as an encoded antigen, including e.g., a transmembrane domain of a SARS-CoV-2 S protein when attached to an antigen of a SARS-CoV-2 S protein).

[00782] A transmembrane domain can be N-terminal, C-terminal, or internal to an encoded polypeptide. A coding sequence of a transmembrane element is typically placed in frame (i.e., in the same reading frame), 5', 3', or internal to coding sequences of sequences (e.g., sequences encoding polypeptide(s)) with which it is to be linked.

[00783] In some embodiments, a transmembrane region comprises or is a transmembrane domain of a SARS-CoV-2 S protein or a transmembrane domain of a SARS-CoV-2 S protein and a C-terminal, membrane adjacent sequence (where the membrane adjacent sequence optionally has a C-terminal truncation (e.g., a 19 amino acid or 37 amino acid C-terminal truncation).

[00784] Transmembrane regions are known in the art, any of which can be utilized in a SARS-CoV-2 construct described herein. In some embodiments, a transmembrane region comprises or is a transmembrane domain of a SARS-CoV-2 S protein, a transmembrane domain of a SARS-CoV-2 S protein with a C-terminal truncation (e.g., a 19 amino acid C-terminal truncation). In some embodiments, a transmembrane domain is a heterologous transmembrane domain. As used herein, "heterologous" refers to an amino acid sequence or nucleotide sequence that is from a different species than the species of a disease specific antigen (e.g., viral antigen) that is within the same polypeptide or nucleotide sequence. For a polypeptide comprising a SARS-CoV-2 antigen (e.g., a truncated SI subdomain) a heterologous sequence would be a sequence of non-SARS-CoV-2 origin.

[00785] In some embodiments, a transmembrane domain comprises or is a transmembrane domain of Hemagglutinin (HA) of Influenza virus, Env of HIV-1, equine infectious anaemia virus (EIAV), murine leukaemia virus (MLV), mouse mammary tumor virus, G protein of vesicular stomatitis virus (VSV), Rabies virus, or a seven transmembrane domain receptor.

[00786] In some embodiments, a mRNA construct described herein comprises a SARS-CoV-2 transmembrane domain (e.g., a polypeptide comprising: a sequence corresponding to residues 1207 to 1236 of SEQ ID NO: 1; EQYIKWPWYIWLGFIAGLIAIVMVTIMLCC; or fragments or variants thereof); a PIV5-F transmembrane domain (e.g., a polypeptide comprising: a sequence corresponding to residues 480-517 of the PIV5-F polypeptide; a sequence corresponding to residues 485-517 of the PIV5-F polypeptide;

ATTTSVLSIIAIALGSLGLILIILLSVWWKTIWA; or VLSIIAIALGSLGLILIILLSWV; or a variant or fragment thereof); or a HeV-F transmembrane domain (e.g., a polypeptide comprising an sequence corresponding to residues 479-526 of a HeV-F polypeptide; residues 484-521 of a HeV-F polypeptide; VLSIIAIALGSLGLILIILLSWV; or ISMLSMIILYVLSIAALCIGLITFISFVIVEKK; variants thereof; or fragments thereof).

[00787] In some embodiments, a polypeptide comprises a C-terminal, membrane proximal region of a SARS- CoV-2 S protein (e.g., a polypeptide comprising a sequence that corresponds to amino acids 1237-1245 of SEQ ID NO: 1; or MTSCCSCLKGCCSCGSCC). In some embodiments, a polypeptide comprises a short stretch of a membrane proximal sequence of the SARS-CoV-2 S protein (e.g., an amino acid sequence corresponding to residues 1209-1217 of SEQ ID NO: 1), C-terminal to (e.g., immediately C-terminal to, or connected by a linker to) a transmembrane domain (e.g., a transmembrane domain of a SARS-CoV-2 S protein). In some embodiments, a polypeptide comprises a VSV-G transmembrane domain. In some embodiments, a VSV-G transmembrane can provide the added benefit of inducing formation of viral-like particles (VLP) when attached to immunogenic polypeptides, which can further improve immunogenicity of a delivered construct, a VSV-G transmembrane domain, optionally including a short membrane proximal sequence (e.g., a signal portion of a membrane proximal active domain (e.g., a polypeptide comprising:

IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or

FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI, variants thereof, or fragments thereof)).

[00788] Exemplary transmembrane are provided in the following Tables 4 and 5: Table 4: Exemplary transmembrane domains (amino acid sequences)

Table 5: Bcemplary nucleotide sequences encoding transmembrane domains

[00789] According to certain embodiments, a transmembrane domain is fused, either directly or through a linker, e.g., a glycine/serine linker, to a SARS-CoV-2 S protein, a variant thereof, or a fragment thereof, i.e., the antigenic peptide or protein. Accordingly, in one embodiment, a transmembrane domain is fused to the above described amino acid sequences derived from SARS-CoV-2 S protein or immunogenic fragments thereof (antigenic peptides or proteins) comprised by the vaccine antigens described above (which may optionally be fused to a signal peptide and/or trimerization domain as described above).

[00790] Such transmembrane domains are preferably located at the C-terminus of the antigenic peptide or protein, without being limited thereto. Preferably, such transmembrane domains are located at the C-terminus of the trimerization domain, if present, without being limited thereto. In one embodiment, a trimerization domain is present between the SARS-CoV-2 S protein, a variant thereof, or a fragment thereof, i.e., the antigenic peptide or protein, and the transmembrane domain.

[00791] Transmembrane domains as defined herein preferably allow the anchoring into a cellular membrane of the antigenic peptide or protein as encoded by the RNA.

[00792] In one embodiment, the transmembrane domain sequence as defined herein includes, without being limited thereto, the transmembrane domain sequence of SARS-CoV-2 S protein, in particular a sequence comprising the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1 or a functional variant thereof. [00793] In one embodiment, a transmembrane domain sequence comprises the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1, or a functional fragment of the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1. In one embodiment, a transmembrane domain sequence comprises the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1.

[00794] In one embodiment, RNA encoding a transmembrane domain sequence (i) comprises the nucleotide sequence of nucleotides 3619 to 3762 of SEQ ID NO: 2, 8 or 9, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 3619 to 3762 of SEQ ID NO: 2, 8 or 9, or a fragment of the nucleotide sequence of nucleotides 3619 to 3762 of SEQ ID NO: 2, 8 or 9, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 3619 to 3762 of SEQ ID NO: 2, 8 or 9; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1, or a functional fragment of the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1. In one embodiment, RNA encoding a transmembrane domain sequence (i) comprises the nucleotide sequence of nucleotides 3619 to 3762 of SEQ ID NO: 2, 8 or 9; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1.

[00795] In one embodiment, the vaccine antigens described above comprise a contiguous sequence of SARS-CoV-2 coronavirus spike (S) protein that consists of or essentially consists of the above described amino acid sequences derived from SARS-CoV-2 S protein or immunogenic fragments thereof (antigenic peptides or proteins) comprised by the vaccine antigens described above. In one embodiment, the vaccine antigens described above comprise a contiguous sequence of SARS-CoV-2 coronavirus spike (S) protein of no more than 220 amino acids, 215 amino acids, 210 amino acids, or 205 amino acids.

[00796] In one embodiment, the RNA encoding the antigen molecule is expressed in cells of the subject to provide the antigen molecule. In one embodiment, expression of the antigen molecule is at the cell surface or into the extracellular space. In one embodiment, the antigen molecule is presented in the context of MHC. In one embodiment, the RNA encoding the antigen molecule is transiently expressed in cells of the subject. In one embodiment, after administration of the RNA encoding the antigen molecule, in particular after intramuscular administration of the RNA encoding the antigen molecule, expression of the RNA encoding the antigen molecule in muscle occurs. In one embodiment, after administration of the RNA encoding the antigen molecule, expression of the RNA encoding the antigen molecule in spleen occurs. In one embodiment, after administration of the RNA encoding the antigen molecule, expression of the RNA encoding the antigen molecule in antigen presenting cells, preferably professional antigen presenting cells occurs. In one embodiment, the antigen presenting cells are selected from the group consisting of dendritic cells, macrophages and B cells. In one embodiment, after administration of the RNA encoding the antigen molecule, no or essentially no expression of the RNA encoding the antigen molecule in lung and/or liver occurs. In one embodiment, after administration of the RNA encoding the antigen molecule, expression of the RNA encoding the antigen molecule in spleen is at least 5-fold the amount of expression in lung.

[00797] In some embodiments, the methods and agents, e.g., RNA compositions, described herein following administration, in particular following intramuscular administration, to a subject result in delivery of the RNA encoding a vaccine antigen to lymph nodes and/or spleen. In some embodiments, RNA encoding a vaccine antigen is detectable in lymph nodes and/or spleen 6 hours or later following administration and preferably up to 6 days or longer.

[00798] In some embodiments, the methods and agents, e.g., mRNA compositions, described herein following administration, in particular following intramuscular administration, to a subject result in delivery of the RNA encoding a vaccine antigen to B cell follicles, subcapsular sinus, and/or T cell zone, in particular B cell follicles and/or subcapsular sinus of lymph nodes.

[00799] In some embodiments, the methods and agents, e.g., mRNA compositions, described herein following administration, in particular following intramuscular administration, to a subject result in delivery of the RNA encoding a vaccine antigen to B cells (CD19+), subcapsular sinus macrophages (CD169+) and/or dendritic cells (CDllc+) in the T cell zone and intermediary sinus of lymph nodes, in particular to B cells (CD19+) and/or subcapsular sinus macrophages (CD169+) of lymph nodes.

[00800] In some embodiments, the methods and agents, e.g., mRNA compositions, described herein following administration, in particular following intramuscular administration, to a subject result in deliver/ of the RNA encoding a vaccine antigen to white pulp of spleen.

[00801] In some embodiments, the methods and agents, e.g., mRNA compositions, described herein following administration, in particular following intramuscular administration, to a subject result in delivery of the RNA encoding a vaccine antigen to B cells, DCs (CDllc+j, in particular those surrounding the B cells, and/or macrophages of spleen, in particular to B cells and/or DCs (CDllc+).

[00802] In one embodiment, the vaccine antigen is expressed in lymph node and/or spleen, in particular in the cells of lymph node and/or spleen described above.

[00803] The peptide and protein antigens suitable for use according to the present disclosure typically include a peptide or protein comprising an epitope of SARS-CoV-2 S protein or a functional variant thereof for inducing an immune response. The peptide or protein or epitope may be derived from a target antigen, i.e. the antigen against which an immune response is to be elicited. For example, the peptide or protein antigen or the epitope contained within the peptide or protein antigen may be a target antigen or a fragment or variant of a target antigen. The target antigen may be a coronavirus S protein, in particular SARS-CoV-2 S protein.

[00804] The antigen molecule or a procession product thereof, e.g., a fragment thereof, may bind to an antigen receptor such as a BCR or TCR carried by immune effector cells, or to antibodies. Mu/timerization Regions

[00805] In some embodiments, a SARS-CoV-2 construct as described herein includes one or more multimerization regions (e.g., a heterologous multimerization region).

[001] In some embodiments, a heterologous multimerization region comprises a dimerization, trimerization or tetra merizati on region.

[00806] In some embodiments, a multimerization region is one described in W02017/081082, which is incorporated herein by reference in its entirety {e.g., SEQ ID NOs: 1116-1167, or fragments or variants thereof). Exemplary trimerization and tetramerization regions include, but are not limited to, engineered leucine zippers, fibritin domain from enterobacteria phage T4, GCN4pll, GCN4-pll, and p53.

[00807] According to certain embodiments, a trimerization domain is fused, either directly or through a linker, e.g., a glycine/serine linker, to a SARS-CoV-2 S protein, a variant thereof, or a fragment thereof, i.e., the antigenic peptide or protein. Accordingly, in one embodiment, a trimerization domain is fused to the above described amino acid sequences derived from SARS-CoV-2 S protein or immunogenic fragments thereof (antigenic peptides or proteins) comprised by the vaccine antigens described above (which may optionally be fused to a signal peptide as described above).

[00808] In some embodiments, a trimerization domains is located at the C-terminus of the antigenic peptide or protein, without being limited thereto. Trimerization domains as defined herein can allow for the trimerization of the antigenic peptide or protein as encoded by the RNA. Examples of trimerization domains as defined herein include, without being limited thereto, foldon, the natural trimerization domain of T4 fibritin. The C-terminal domain of T4 fibritin (foldon) is obligatory for the formation of the fibritin trimer structure and can be used as an artificial trimerization domain. In one embodiment, the trimerization domain as defined herein includes, without being limited thereto, a sequence comprising the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10 or a functional variant thereof. In one embodiment, the trimerization domain as defined herein includes, without being limited thereto, a sequence comprising the amino acid sequence of SEQ ID NO: 10 or a functional variant thereof.

[00809] In one embodiment, a trimerization domain comprises the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10, or a functional fragment of the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10. In one embodiment, a trimerization domain comprises the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10.

[00810] In one embodiment, RNA encoding a trimerization domain (i) comprises the nucleotide sequence of nucleotides 7 to 87 of SEQ ID NO: 11, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 7 to 87 of SEQ ID NO: 11, or a fragment of the nucleotide sequence of nucleotides 7 to 87 of SEQ ID NO: 11, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 7 to 87 of SEQ ID NO: 11; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10, or a functional fragment of the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10. In one embodiment, RNA encoding a trimerization domain (i) comprises the nucleotide sequence of nucleotides 7 to 87 of SEQ ID NO: 11; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10.

[00811] In one embodiment, a trimerization domain comprises the amino acid sequence SEQ ID NO: 10, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 10, or a functional fragment of the amino acid sequence of SEQ ID NO: 10, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 10. In one embodiment, a trimerization domain comprises the amino acid sequence of SEQ ID NO: 10.

[00812] In one embodiment, RNA encoding a trimerization domain (i) comprises the nucleotide sequence of SEQ ID NO: 11, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 11, or a fragment of the nucleotide sequence of SEQ ID NO: 11, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 11; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 10, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 10, or a functional fragment of the amino acid sequence of SEQ ID NO: 10, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 10. In one embodiment, RNA encoding a trimerization domain (i) comprises the nucleotide sequence of SEQ ID NO: 11; and/or (ii) encodes an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 10.

[00813] Such trimerization domains are preferably used in order to promote trimerization of the encoded antigenic peptide or protein. More preferably, a trimerization domain as defined herein is fused to an antigenic peptide or protein as defined herein.

[00814] Accordingly, in particularly preferred embodiments, the RNA described herein comprises at least one coding region encoding an antigenic peptide or protein and a trimerization domain as defined herein, said trimerization domain preferably being fused to the antigenic peptide or protein, more preferably to the C-terminus of the antigenic peptide or protein.

[00815] Among other things, the present disclosure provides approaches for producing higher order oligomers (e.g., oligomers comprising more than 3 SARS-CoV-2 antigens). In some embodiments, polypeptides described in here can induce highly multimeric oligomers (e.g., oligomers approximately 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, or 60 or more SARS-CoV-2 antigens), generate an improved immune response (e.g., as compared to a composition comprising the same amount of RNA (in terms of mass or moles)) encoding a polypeptide producing a monomer or an oligomer comprising fewer SARS-CoV-2 antigens), and/or can display antigenic polypeptides in a confirmation that is preferred for generating an immune response.

[00816] In some embodiments, an RNA can encode a polypeptide comprise two or more antigenic regions (e.g., two or more RBDs, three or more RBDs, four or more RBDs, or five or more RBDs), e.g., as described in Gao et al., the contents of which are incorporated by reference herein in their entirety.

[00817] In some embodiments, an RNA can encode two or more antigenic regions (e.g., can encode a polypeptide comprising two or more RBD polypeptides), and further comprise a multimerization domain (e.g., a T4 fibritin domain). For example, in some embodiments, a polypeptide provides two or more (e.g., 2, 3, or 4) antigen regions (e.g., RBD polypeptides) and a multimerization (e.g., trimerization) domain. In some embodiments, a polypeptide provided herein comprises two RBD polypeptides and a trimerization domain, such that an oligomer comprising six RBD polypeptides (a "trimer of dimers", where each "dimer" refers to a polypeptide comprising two RBD polypeptides) can be formed. [00818] In some embodiments, a multimerization can induce highly multivalent oligomers (e.g., oligomers comprising 10 or more antigenic polypeptides).

[00819] In some embodiments, a multimerization domain can induce multimerization of 10, 15, 20, 24, 25, 30, 35, 40, 45, 50, 55, 60, or more antigenic polypeptides.

[00820] In some embodiments, multimerization domains are selected so as to reduce an immune response generated against the multimerization domain itself. For example, in some embodiments, a relatively small multimerization domain is used (e.g., a multimerization domain comprising about 100 amino acids or less and/or a multimerization domain that comprises less than 20% of the total amino acids in a polypeptide). Additionally or alternatively, in some embodiments, a multimerization domain is used that forms an oligomer structure in which (i) the multimerization domain is not freely accessible in solution, and/or has reduced solvent accessibility as compared to a relevant comparator (e.g., other multimerization domains commonly used in commercial vaccines, e.g., a T4 fibritin domain); and/or (ii) the majority of antigen is freely accessible in solution and/or forms the majority of the solvent exposed surface area of an oligomer (e.g., 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, or 80% or more).

[00821] Suitable multimerization domains include, e.g., those described in, Lainscek, Dusko, et al. "A nanoscaffolded spike-RBD vaccine provides protection against SARS-CoV-2 with minimal anti-scaffold response," Vaccines 9.5 (2021): 431; Joyce, M. Gordon, et al. "SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity," Cell reports 37.12 (2021); Joyce, M. Gordon, et al. "A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates," Science translational medicine 14.632 (2021): eabi5735; Wang, Chong, et al. "Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice." Antiviral research 140 (2017): 55-61; Johnston, Sara C., et al. "A SARS-CoV-2 spike ferritin nanoparticle vaccine is protective and promotes a strong immunological response in the cynomolgus macaque coronavirus disease 2019 (COVID-19) model," Vaccines 10.5 (2022): 717; Zhang, Baoshan, et al. "A platform incorporating trimeric antigens into selfassembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone," Scientific reports 10.1 (2020): 18149; Malhi, Harman, et al. "Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge." Cell Reports Medicine 3.6 (2022); and WO2022043449A1, the contents of each of which is incorporated by reference herein in their entirety.

[00822] In some embodiments, an mRNA construct described herein comprises a multimerization domain listed in Table 14.

Table 14: Exemplary Multimerization Domains

[00823] In some embodiments, a multimerization domain comprises a ferritin domain (e.g., as described in Table II). In some embodiments a multimerization domain comprises a ferritin domain that has been modified to reduced autoimmunity (e.g., as described in Kanekiyo, Masaru, et al. "Rational design of an Epstein-Barr virus vaccine targeting the receptor-binding site," Cell 162.5 (2015): 1090-1100, the contents of which are incorporated by reference herein in their entirety).

Domains for Inducing Formation of Viral Like Particles

[00824] Among other things, the present disclosure describes RNAs that can induce formation of enveloped VLPs that present one or more coronavirus (e.g., SARS-CoV-2) antigens (e.g., full length S protein, RBD polypeptide, NTD polypeptide, truncated SI subdomain, and/or S2 polypeptide, variants thereof, or immunogenic fragments thereof, e.g., as described herein) when transfected into a cell (e.g., by administering a nanoparticle- formulated RNA to a subject).

[00825] As-used herein, a Virus Like Particle or Viral Like Particle (VLP) refers to a non-infectious, selfassembling particle, which structurally resembles a virus, but which lacks genetic material necessary to replicate. Presentation of antigens via VLPs has previously been shown to provide strong immune responses, including, e.g., a high immune response, B cell activation, and high-titer antbody production in the absence of adjuvants. Without wishing to be bound by theory, this strong immune response is thought to be potentially the result of surface displaying an antigen in a structured, densely repeated amino acid motifs. Nanometer-sized VLPs can also be taken up by antigen-presenting cells and degrading, ultimately leading to T cell activation. See, e.g., Zeltins, Andris. "Construction and characterization of virus-like particles: a review," Molecular biotechnology 53.1 (2013): 92-107, which is incorporated by reference herein in its entirety.

[00826] In some embodiments, RNA described herein can induce formation of VLPs by exploiting viral machinery (e.g., one or more proteins or domains thereof) that induce viral particle formation in their native context. Exemplary strategies for producing VLPs include, e.g., those described in Zeltins, Andris. "Construction and characterization of virus-like particles: a review," Molecular biotechnology 53.1 (2013): 92-107; Yin, Shuanghui, et al. "Self-assembly of virus-like particles of porcine circovirus type 2 capsid protein expressed from Escherichia coli." Virology journal 7 (2010): 1-5; Wu, Pei-Ching, et al. "Characterization of porcine circovirus type 2 (PCV2) capsid particle assembly and its application to virus-like particle vaccine development," Applied microbiology and biotechnology 95 (2012): 1501-1507; Grgacic, Elizabeth VL, and David A. Anderson "Virus-like particles: passport to immune recognition." Methods 40.1 (2006): 60-65, the contents of each of which is incorporated by reference herein in its entirety.

[00827] The present disclosure describes new constructs and strategies for producing antigen-presenting VLPs in a subject (in particular coronavirus antigen presenting VLPs, which can, in some embodiments, be provided in mRNA compositions, and which can provide certain advantages as compared to previous approaches). EABR Domains

[00828] In some embodiments, a polypeptide comprises an endosomal sorting complex required for transport (ESCRT)- and ALG-2-interacting protein X (ALIX) binding region (collectively referred to as EABR), e.g., as described in Hoffmann, Magnus AG, et al. "ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines." Cell 186.11 (2023): 2380-2391, the contents of which are incorporated by reference herein in their entirety.

[00829] An EABR recruits ESCRT machinery required for the scission of membrane necks in processes such as, e.g., the budding of HIV-1 and cytokinesis. This is excomplished via recruitment of the ESCRT-I compelx and the ESCRT associated protein ALIX to the midbody (structure that teathces two daughter cells) by the protein CEP55. Thus, in some embodiments, when an EABR is attached to a poplypeptide comprising a SARS-CoV-2 antigen (e.g., at the C-terminus of the polypeptide), VLPs can be produced by cells transfected with RNA encoding the polypeptide, where the VLPs comprise a SARS-CoV-2 antigen (e.g., an antigen described herein). [00830] In some embodiments, an EABR is a human EABR. In some embodiments, a human EABR comprises an amino acid sequence of

FNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLLAKIFELEKKTETAAHSLP or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00831] In some embodiments, an EABR comprises a viral protein or a fragment thereof. In some embodiments, an EABR comprises an EABR of an HIV protein. In some embodiments, an EABR comprises an EABR of an HIV-1 Gag protein.

[00832] In some embodiments, an EABR comprises an HIV Gag C-terminal p6 peptide or one or more fragments thereof, e.g., as described in Meusser, Birgit, Bettina Purfuerst, and Friedrich C. Luft. "HIV-1 Gag release from yeast reveals ESCRT interaction with the Gag N-terminal protein region." Journal of Biological Chemistry 295.52 (2020): 17950-17972, the context of which are incorporated by reference herein in their entirety.

[00833] In some embodiments, an HIV Gag C-terminal p6 peptide comprises an amino acid sequence of LQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00834] In some embodiments, a HIV Gag C-terminal p6 peptide comprises an amino acid sequence of DKELYPLTSLRSLFGN or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00835] In some embodiments, an EABR comprises a p9 Alix peptide. In some embodiments, a p9 Alix peptide comprises an amino acid sequence of TQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00836] In some embodiments, an EABR comprises a fragment of an EBOV VP40 matrix protein, e.g., as described in Han, Ziying, et al. "ALIX rescues budding of a double PTAP/PPEY L-domain deletion mutant of Ebola VP40: a role for ALIX in Ebola virus egress." The Journal of infectious diseases 212.suppl_2 (2015): S138-S145, the contents of which are incorporated by reference herein in their entirety.

[00837] In some embodiments, a fragment of an EBOV VP40 matrix protein an amino acid sequence of VILPTAPPEYMEA or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00838] In some embodiments, an EABR comprises a fragment of an EBOV VP40 matrix protein and a p6 Alix peptide. In some embodiments, an EABR comprises a peptide comprising an amino acid sequence of VILPTAPPEYMEA, or an amino acid sequence having 1, 2, 3, or 4, modifications thereto, and a peptide having an amino acid sequence of DKELYPLTSLRSLFGN or an amino acid sequence having 1, 2, 3, or 4 modfications thereto. In some embodiments, a fragment of an EBOV VP40 matrix protein and a p6 Alix peptide are directly adjacent to one another. In some embodiments, a fragment of an EBOV VP40 matrix protein and a p6 Alix protein are connected by a flexible linker (e.g., as described herein, including, e.g., a flexible linker comprising a peptide comprising an amino acid sequence of GSGSGS). In some embodiments, an EABR comprises an amino acid sequence of LPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00839] In some embodiments, an EABR comprises a fragment of an EBOV VP40 matrix protein and a p9 Alix peptide. In some embodiments, an EABR comprises a peptide having an amino acid sequence of VILPTAPPEYMEA, or an amino acid sequence having 1, 2, 3, or 4, modifications thereto, and a peptide having an amino acid sequence of TQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE or an amino acid sequence having 1, 2, 3, or 4 modfications thereto. In some embodiments, a fragment of an EBOV VP40 matrix protein and a p9 Alix peptide are directly adjacent to one another. In some embodiments, a fragment of an EBOV VP40 matrix protein and a p9 Alix peptide are connected by a flexible linker (e.g., as described herein, including, e.g., a flexible linker comprising a peptide comprising an amino acid sequence of GSGSGS). In some embodiments, an EABR comprises an amino acid sequence of VILPTAPPEYMEAGSGSGSTQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00840] In some embodiments, a polypeptide comprises one or more minimal TSG 101 and/or Alix motifs, optionally connected via flexible linkers. In some embodiments, a polypeptide comprises 1, 2, 3, 4, or more minimal TSG 101 motifs and 1, 2, 3, or 4 minimal Alix motifs. In some embodiments, a polypeptide comprises 2, minimal TSG 101 motifs and 2 minimal Alix motifs. In some embodiments, a minimal TSG 101 motif comprises an amino acid sequence of PTAP. In some embodiments, a minimal TSG 101 motif comprises an amino acid sequence of PTAPPEY. In some embodiments, a minimal TSG 101 motif comprises an amino acid sequence of PSAP.

[00841] In some embodiments, a minimal Alix motif comprises an amino acid sequence of LYPLTSLRSL.

[00842] In some embodiments a polypeptide comprises 1, 2, 3, 4, or 5 minimal TSG 101 motifs and 1 or 2 minimal Alix motifs. In some embodiments a polypeptide comprises 2 or 3 minimal TSG 101 motifs and 1 or 2 minimal Alix motifs. In some embodiments a polypeptide comprises 3 minimal TSG 101 motifs and 1 minimal Alix motifs. In some embodiments, an EABR comprises a peptide comprising an amino acid sequence of PTAPPEY, a peptide comprising an amino acid sequence of PTAP, and/or a peptide comprising an amino acid sequence of PSAP. In some embodiments, an EABR comprises a peptide comprising an amino acid sequence of PTAPPEY, a peptide comprising an amino acid sequence of PTAP, a peptide comprising an amino acid sequence of PSAP, and/or a peptide comprising an amino acid sequence of YPDLNLDSL, optionally wherein each of the peptides are connected to one another directly or via a flexible linker (e.g., a GS linker comprising about 5 amino acids, including e.g., GSGSGS. In some embodiments, an EABR comprises an amino acid sequence of GSGSGSPTAPPEYGSGSGSLYPLTSLRSLGSGSGSPTAPGSGSGSLYPDLNLDSLGSGSGSPSAP, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto.

[00843] In some embodiments, a polypeptide comprising an EABR sequence comprises a transmembrane domain (e.g., a transmembrane of a SARS-CoV-2 S protein (e.g., as described herein, optionally with a C-terminal proximal sequence). An exemplary polypeptide comprising a SARS-CoV-2 antigen and an EABR sequence is shown in Figure 6, and two exemplary polypeptide sequences are provided in Table IV.

[00844] In some embodiments, a polypeptide comprising an EABR further comprises a sequence that prevents endocytosis of the polypeptide (referred to herein as an endocytosis prevention motif (EPM)). In one embodiment, an EPM is an EPM of a cytoplasmic tail of an Fc gamma receptor FcgRII-Bl (e.g., a murine Fc gamma receptor FcgRII-Bl). In some embodiments, an EPM comprises an amino acid sequence of example of a sequence that can prevent endocytosis of a polypeptide is a EPM comprises an amino acid sequence of ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY, or sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical to ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY, or a seuqence that comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 modifications relative to ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY.

VSV-G Domains

[00845] In some embodiments, a sequence capable of inducing VLP formation when attached to a polypeptide comprising a coronavirus antigen is a sequence that comprises a VSV-G transmembrane domain. [00846] In some embodiments, a VSV-G transmembrane domain includes a short membrane proximal sequence (e.g., a signal portion of a membrane proximal ectodomain (e.g., a VSV-G ectodomain, including, e.g., polypeptide comprising: IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK, FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI

QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI, or FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI, variants thereof, or fragments thereof)).

[00847] In some embodiments, a polypeptide comprises a peptide comprising an amino acid sequence of IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, thereto.

[00848] In some embodiments, a polypeptide comprises a peptide comprising an amino acid sequence of FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, thereto.

[00849] In some embodiments, a polypeptide comprises a peptide comprising an amino acid sequence of QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, thereto.

[00850] In some embodiments, a polypeptide comprises a peptide comprising an amino acid sequence of FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, thereto.

[00851] In some embodiments, a polypeptide comprises a VSV-G ectodomain and a transmembrane domain. In some embodiments, the transmembrane domain is not a VSV-G transmembrane domain (e.g., instead, comprises a transmembrane described herein, including, e.g., a SARS-CoV-2 S protein transmembrane domain). In some embodiments, the transmembrane domain is a VSV-G transmembrane domain. In some embodiments, a VSV-G transmembrane domain comprises an amino acid sequence of KLKHTKKRQIYTDIEMNRLGK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, thereto.

[00852] In some embodiments, a VSV-G transmembrane domain (with optional membrane proximal sequence (e.g., ectodomain sequence)) is at the C-terminus of a polypeptide.

[00853] In some embodiments, a C-terminal region of a SARS-CoV-2 S protein (e.g., a polypeptide comprising a sequence that corresponds to amino acids 1237-1245 of SEQ ID NO: 1; or MTSCCSCLKGCCSCGSCC). In some embodiments, a polypeptide comprises a short stretch of a membrane proximal sequence of the SARS-CoV-2 S protein (e.g., an amino acid sequence corresponding to residues 1209- 1217 of SEQ ID NO: 1), C-terminal to (e.g., immediately C-terminal to, or connected by a linker to) a transmembrane domain (e.g., a transmembrane domain of a SARS-CoV-2 S protein).

PCV Domains [00854] In some embodiments, portions of a capsid protein of Porcine circovirus 2 (PVC-2) can be attached to a polypeptide comprising a coronavirus antigen (e.g., as as depicted in Figure 5). In some embodiments, an RNA (e.g., mRNA) construct described herein encodes a polypeptide depicted in Figure 5. In some embodiments, an RNA encodes a polypeptide comprising a coronavirus antigen (e.g., as described herein) and portions of a PVC-2 capside protein. In some embodiments, the portions of PVC-2 capsid proteins comprise an amino acid sequence describe dherien. In some embodiments, the portions of PVC-2 capsid proteins comprise an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to an amino acid sequence described in the present disclosure.

SARS-CoV-2 VLPs

[00855] In some embodiments, compositions capable of forming VLPs comprise two or more mRNA molecules: (i) one or more mRNA molecules, each of which encodes a polypeptide comprising a coronavirus antigen and (ii) one or more mRNA molecules, each of which encodes a polypeptide that, separately or together can induce formation of a VLP in vivo. In some embodiments, a composition comprises: (i) one or more RNA (e.g., mRNA) constructs, each encoding a coronavirus antigen, and (ii) one or more RNA (e.g., mRNA) constructs encoding a SARS-CoV-2 M polypeptide and/or one or more RNA (e.g., mRNA) constructs encoding a SARS-CoV-2 E polypeptide (e.g., as described in Lu, Jing, et al. "A COVID-19 mRNA vaccine encoding SARS-CoV-2 virus-like particles induces a strong antiviral-like immune response in mice." Cell research 30.10 (2020): 936-939, the contents of which are incorporated by reference in their entirety. In some embodiments, the RNA (e.g., mRNA) encoding a SARS-CoV-2 M protein and the RNA (e.g., mRNA) encoding a SARS-CoV-2 E protein are present at a molar ratio of 1:1. In some embodiments, the molar ratio of: (i) the one or more RNA (e.g., mRNA) constructs encoding a coronavirus antigen, (ii) the RNA (e.g., mRNA) encoding a SARS-CoV-2 M protein, and (iii) the RNA (e.g., mRNA) encoding a SARS-CoV-2 E protein is l-5:l-5:l-5; 1:5:5, 1:4:4; 1:3:3; 1:2:2; or 1:1:1.

[00856] Alternatively, in some embodiments, an RNA (e.g., mRNA) construct described herein encodes a polypeptide comprising: (i) a coronavirus antigen (e.g., a full-length S protein, an RBD polypeptide, an NTD polypeptide, and/or an S2 polypeptide, immunogenic fragments thereof, and/or variants thereof), and (ii) one or more sequences that, together or separately, can induce formation of a VLP when the polypeptide is expressed in a subject.

[00857] The present application is the first to recognize that certain SARS-CoV-2 components can be incorporated into a polypeptide comprising a coronavirus antigen (e.g., a coronavirus S protein or an immunogeneic fragment thereof) and used to induce vesicle formation and antigen presentation. Without wishing to be limited by theory, such constructs provide the advantage of reducing the number of RNA (e.g., mRNA) constructs that need to be administered to a subject, which in turn reduces the amount of RNA that needs to be administered to a subject. Reducing the amount of mRNA encoding a coronavirus antigen can be advantageous, e.g., because it can reduce the severity and/or incidence of undesired side-effects and/or allow for administration of higher amounts of vaccine.

[00858] Provided in the below Table XX are exemplary domains that can be used to induce VLP formation. In some embodiments, (i) an RNA encoding M protein design 1, an RNA encoding E Protein Design 1, (ii) an RNA encoding M protein design 1, an RNA encoding E Protein Design 2, (iii) an RNA encoding M protein design 2, an RNA encoding E Protein Design 1, or (iv) an RNA encoding M protein design 2, an RNA encoding E Protein Design 2, are coadministered with an RNA encoding a coronavirus antigen (e.g., as described herein). Coadministering can be performe, e.g., using a population of LNPs in which all three RNAs have been coformualted or populations where the three RNAs have been separately formatted.

[00859] In some embodiments, an RNA comprises a nucleotide sequence that encodes a polypeptide comprising one or more more of the proteins listed in Table XX and an antigen of a coronavirus S protein (e.g, an antigen described herein. In some embodiments, an RNA comprises a nucleotide sequence encoding a polypeptide comprising (i) a M protein design 1 and E Protein Design 1, (ii) M protein design 1 and E Protein Design 2, (iii) M protein design 2 and E Protein Design 1, or (iv) M protein design 2, an RNA encoding E Protein Design 2, and also a coronavirus S protein antigen (e.g., as described herein).

[00860] Table XX: Exemplary SARS-CoV-2 Polypeptides for Inducing VLP Formation

[00861] In some embodiments, the present disclosure provides an insight that a VLP can be produced that comprises multiple coronavirus antigens (e.g., antigens of different SARS-CoV-2 variants or stains or different antigens of the same SARS-CoV-2 variant or strain). In some embodiments, an RNA (e.g., mRNA) composition capable of forming VLPs when administered to a subject comprises two or more mRNA constructs, each encoding a coronavirus antigen, for example:

• two or more mRNA constructs, each encoding a coronavirus antigen (e.g., RBD polypeptide, NTD polypeptide, or full length S protein) of a different coronavirus (e.g., different betacoronaviruses; different sarbecoviruses; a SARS-CoV-2 virus and a SARS-CoV-1 virus, or a SARS-CoV-2 virus and a MERS virus); or

• two or more mRNA constructs each encoding an antigen (e.g., an NTD polypeptide, RBD polypeptide, or full length S protein) of a different coronavirus (e.g., SARS-CoV-2) strain or variant.

[00862] In some embodiments, the present disclosure provides the insight that a VLP can be produced that comprises multiple coronavirus antigens (e.g., antigens of different SARS-CoV-2 variants or stains or different antigens of the same SARS-CoV-2 variant or strain). In some embodiments, an mRNA composition capable of forming VLPs when administered to a subject comprises two or more mRNA constructs, each encoding a coronavirus antigen, for example:

• two or more mRNA constructs, each encoding a coronavirus antigen (e.g., RBD polypeptide, NTD polypeptide, or full length S protein) of a different coronavirus (e.g., different betacoronaviruses; different sarbecoviruses; a SARS-CoV-2 virus and a SARS-CoV-1 virus, or a SARS-CoV-2 virus and a MERS virus); or

• two or more mRNA constructs each encoding an antigen (e.g., an NTD polypeptide, RBD polypeptide, or full length S protein) of a different coronavirus (e.g., SARS-CoV-2) strain or variant.

Linkers [00863] In some embodiments, a SARS-CoV-2 construct described herein includes one or more linkers. In some embodiments, a linker is or comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 or more amino acids. In some embodiments, a linker is or comprises no more than about 30, 25, 20, 15, 10 or fewer amino acids. A linker can include any amino acid sequence and is not limited to any particular amino acids.

[00864] In some embodiments, a linker described herein is a rigid linker. In some embodiments, a rigid linker comprises one or more Pro residues. In some embodiments, a rigid linker comprises one or more repeats of a PA motif, optionally where the PA motif is repeated to a reach a total length of 10-40 amino acids, 10-30 amino acids, 10-20 amino acids, 25-30 amino acids, about 5 amino acids, about 10 amino acids, or about 20 amino acids.

[00865] In some embodiments, a linker described herein is a helical linker. In some embodiments, a helical linker comprises an amino acid sequence of AEAAAKEAAAKA, AEAAAKEAAAKEAAAKA, AEAAAKEAAAKEAAAKEAAAKA, or AEAAAKEAAAKEAAAKEAAAKEAAAKA, or sequences comprising 1, 2, 3, 4, or 5 amino acid modifications thereto.

[00866] In some embodiments, a linker is a flexible linker. As used herein, a flexible linker in the context of a polypeptide refers to an amino acid sequence that connects two protein regions while allowing for movement and interaction between the two protein regions. Flexible linkers often comprise small, non-polar (e.g., Gly) or polar (e.g., Ser or Thr) amino acids acids, which allow for linker flexibility.

[00867] In some embodiments, a linker comprises one or more glycine (G) amino acids. In some embodiments, a linker comprises one or more serine (S) amino acids. In some embodiments, a linker includes amino acids selected based on a cleavage predictor to generate highly-cleavable linkers.

[00868] In some embodiments, a linker is or comprises S-G4-S-G4-S (SEQ ID NO: 334). In some embodiments, a linker is or comprises GSPGSGSGS (SEQ ID NO: 335). In some embodiments, a linker is or comprises GGSGGGGSGG (SEQ ID NO: 336). In some embodiments, a linker is or comprises GSGSGS (SEQ ID NO: 337). In some embodiments, a linker is one presented in Table 5. In some embodiments, a linker is or comprises a sequence as set forth in W02017/081082, which is incorporated herein by reference in its entirety (see SEQ ID NOs: 1509-1565, or a fragment or variant thereof).

[00869] In some embodiments, a SARS-CoV-2 construct described herein comprises a linker between a C- terminal region or fragment thereof and a transmembrane region.

[00870] Exemplary linkers are provided in the following Table X:

Table X: Exemplary linkers

Nucleic acids

[00871] The term "polynucleotide" or "nucleic acid", as used herein, is intended to include DNA and RNA such as genomic DNA, cDNA, mRNA, recombinantly produced and chemically synthesized molecules. A nucleic acid may be single-stranded or double-stranded. RNA includes in vitro transcribed RNA (IVT RNA) or synthetic RNA. According to the present disclosure, a polynucleotide is preferably isolated.

[00872] Nucleic acids may be comprised in a vector. The term "vector" as used herein includes any vectors known to the skilled person including plasmid vectors, cosmid vectors, phage vectors such as lambda phage, viral vectors such as retroviral, adenoviral or baculoviral vectors, or artificial chromosome vectors such as bacterial artificial chromosomes (BAC), yeast artificial chromosomes (YAC), or Pl artificial chromosomes (PAC). Said vectors include expression as well as cloning vectors. Expression vectors comprise plasmids as well as viral vectors and generally contain a desired coding sequence and appropriate DNA sequences necessary for the expression of the operably linked coding sequence in a particular host organism (e.g., bacteria, yeast, plant, insect, or mammal) or in in vitro expression systems. Cloning vectors are generally used to engineer and amplify a certain desired DNA fragment and may lack functional sequences needed for expression of the desired DNA fragments.

[00873] In one embodiment of all aspects of the present disclosure, the RNA encoding the vaccine antigen is expressed in cells such as antigen presenting cells of the subject treated to provide the vaccine antigen. [00874] The nucleic acids described herein may be recombinant and/or isolated molecules.

[00875] In the present disclosure, the term "RNA" relates to a nucleic acid molecule which includes ribonucleotide residues. In preferred embodiments, the RNA contains all or a majority of ribonucleotide residues. As used herein, "ribonucleotide" refers to a nucleotide with a hydroxyl group at the 2'-position of a p-D- ribofuranosyl group. RNA encompasses without limitation, double stranded RNA, single stranded RNA, isolated RNA such as partially purified RNA, essentially pure RNA, synthetic RNA, recombinantly produced RNA, as well as modified RNA that differs from naturally occurring RNA by the addition, deletion, substitution and/or alteration of one or more nucleotides. Such alterations may refer to addition of non-nucleotide material to internal RNA nucleotides or to the end(s) of RNA. It is also contemplated herein that nucleotides in RNA may be non-standard nucleotides, such as chemically synthesized nucleotides or deoxynucleotides. For the present disclosure, these altered RNAs are considered analogs of naturally-occurring RNA.

[00876] In certain embodiments of the present disclosure, the RNA is messenger RNA (mRNA) that relates to a RNA transcript which encodes a peptide or protein. As established in the art, mRNA generally contains a 5' untranslated region (5'-UTR), a peptide coding region and a 3' untranslated region (3'-UTR). In some embodiments, the RNA is produced by in vitro transcription or chemical synthesis. In one embodiment, the mRNA is produced by in vitro transcription using a DNA template where DNA refers to a nucleic acid that contains deoxyribonucleotides.

[00877] In one embodiment, RNA is in vitro transcribed RNA (IVT-RNA) and may be obtained by in vitro transcription of an appropriate DNA template. The promoter for controlling transcription can be any promoter for any RNA polymerase. A DNA template for in vitro transcription may be obtained by cloning of a nucleic acid, in particular cDNA, and introducing it into an appropriate vector for in vitro transcription. The cDNA may be obtained by reverse transcription of RNA.

[00878] In certain embodiments of the present disclosure, RNA described herein is "replicon RNA" or simply a "replicon", in particular "self-replicating RNA" or "self-amplifying RNA". In one particularly preferred embodiment, the replicon or self-replicating RNA is derived from or comprises elements derived from a ssRNA virus, in particular a positive-stranded ssRNA virus such as an alphavirus. Alphaviruses are typical representatives of positive-stranded RNA viruses. Alphaviruses replicate in the cytoplasm of infected cells (for review of the alphaviral life cycle see Jose et al., Future Microbiol., 2009, vol. 4, pp. 837-856). The total genome length of many alphaviruses typically ranges between 11,000 and 12,000 nucleotides, and the genomic RNA typically has a 5'-cap, and a 3' poly(A) tail. The genome of alphaviruses encodes non-structural proteins (involved in transcription, modification and replication of viral RNA and in protein modification) and structural proteins (forming the virus particle). There are typically two open reading frames (ORFs) in the genome. The four non- structural proteins (nsPl-nsP4) are typically encoded together by a first ORF beginning near the 5' terminus of the genome, while alphavirus structural proteins are encoded together by a second ORF which is found downstream of the first ORF and extends near the 3' terminus of the genome. Typically, the first ORF is larger than the second ORF, the ratio being roughly 2:1. In cells infected by an alphavirus, only the nucleic acid sequence encoding non-structural proteins is translated from the genomic RNA, while the genetic information encoding structural proteins is translatable from a subgenomic transcript, which is an RNA molecule that resembles eukaryotic messenger RNA (mRNA; Gould et al., 2010, Antiviral Res., vol. 87 pp. 111-124). Following infection, i.e. at early stages of the viral life cycle, the (+) stranded genomic RNA directly acts like a messenger RNA for the translation of the open reading frame encoding the non-structural poly-protein (nsP1234).

Alphavirus-derived vectors have been proposed for delivery of foreign genetic information into target cells or target organisms. In simple approaches, the open reading frame encoding alphaviral structural proteins is replaced by an open reading frame encoding a protein of interest. Alphavirus-based trans-replication systems rely on alphavirus nucleotide sequence elements on two separate nucleic acid molecules: one nucleic acid molecule encodes a viral replicase, and the other nucleic acid molecule is capable of being replicated by said replicase in trans (hence the designation trans-replication system). Trans-replication requires the presence of both these nucleic acid molecules in a given host cell. The nucleic acid molecule capable of being replicated by the replicase in trans must comprise certain alphaviral sequence elements to allow recognition and RNA synthesis by the alphaviral replicase.

[00879] In one embodiment, RNA described herein may have modified nucleosides. In some embodiments, RNA comprises a modified nucleoside in place of at least one (e.g., every) uridine.

[00880] The term "uracil," as used herein, describes one of the nucleobases that can occur in the nucleic acid of RNA. The structure of uracil is:

[00881] The term "uridine," as used herein, describes one of the nucleosides that can occur in RNA. The structure of uridine is:

[00882] UTP (uridine 5'-tri phosphate) has the following structure:

[00883] Pseudo-UTP (pseudouridine 5'-triphosphate) has the following structure:

[00884] "Pseudouridine" is one example of a modified nucleoside that is an isomer of uridine, where the uracil is attached to the pentose ring via a carbon-carbon bond instead of a nitrogen-carbon glycosidic bond.

[00885] Another exemplary modified nucleoside is Nl-methyl-pseudouridine (mlUJ), which has the structure:

[00886] Nl-methyl-pseudo-UTP has the following structure:

[00887] Another exemplary modified nucleoside is 5-methyl-uridine (m5U), which has the structure:

[00888] In some embodiments, one or more uridine in the RNA described herein is replaced by a modified nucleoside. In some embodiments, the modified nucleoside is a modified uridine.

[00889] In some embodiments, RNA comprises a modified nucleoside in place of at least one uridine. In some embodiments, RNA comprises a modified nucleoside in place of each uridine.

[00890] In some embodiments, the modified nucleoside is independently selected from pseudouridine (qj), Nl-methyl-pseudouridine (mlqj), and 5-methyl-uridine (m5U). In some embodiments, the modified nucleoside comprises pseudouridine (qj). In some embodiments, the modified nucleoside comprises Nl-methyl-pseudouridine (mlqj). In some embodiments, the modified nucleoside comprises 5-methyl-uridine (m5U). In some embodiments, RNA may comprise more than one type of modified nucleoside, and the modified nucleosides are independently selected from pseudouridine (qi), Nl-methyl-pseudouridine (mlqi), and 5-methyl-uridine (m5U). In some embodiments, the modified nucleosides comprise pseudouridine (qj) and Nl-methyl-pseudouridine (mlqj). In some embodiments, the modified nucleosides comprise pseudouridine (qj) and 5-methyl-uridine (m5U). In some embodiments, the modified nucleosides comprise Nl-methyl-pseudouridine (mlqi) and 5-methyl-uridine (m5U). In some embodiments, the modified nucleosides comprise pseudouridine (qi), Nl-methyl-pseudouridine (mlqj), and 5-methyl-uridine (m5U).

[00891] In some embodiments, the modified nucleoside replacing one or more, e.g., all, uridine in the RNA may be any one or more of 3-methyl-uridine (m3U), 5-methoxy-uridine (mo5U), 5-aza-uridine, 6-aza-uridine, 2- thio-5-aza-uridine, 2-thio-uridine (s2U), 4-thio-uridine (s4U), 4-thio-pseudouridine, 2-thio-pseudouridine, 5- hydroxy-uridine (ho5U), 5-aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridine or 5-bromo-uridine), uridine 5- oxyacetic acid (cmo5U), uridine 5-oxyacetic acid methyl ester (mcmo5U), 5-carboxymethyl-uridine (cm5U), 1- carboxymethyl-pseudouridine, 5-carboxyhydroxymethyl-uridine (chm5U), 5-carboxyhydroxymethyl-uridine methyl ester (mchm5U), 5-methoxycarbonylmethyl-uridine (mcm5U), 5-methoxycarbonylmethyl-2-thio-uridine (mcm5s2U), 5-aminomethyl-2-thio-uridine (nm5s2U), 5-methylaminomethyl-uridine (mnm5U), 1-ethyl- pseudouridine, 5-methylaminomethyl-2 -thio-uridine (mnm5s2U), 5-methylaminomethyl-2-seleno-uridine (mnm5se2U), 5-carbamoylmethyl-uridine (ncm5U), 5-carboxymethylaminomethyl-uridine (cmnm5U), 5- carboxymethylaminomethyl-2-thio-uridine (cmnm5s2U), 5-propynyl-uridine, 1-propynyl-pseudouridine, 5- taurinomethyl-uridine (rm5U), 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine(Tm5s2U), 1- taurinomethyl-4-thio-pseudouridine), 5-methyl-2-thio-uridine (m5s2U), l-methyl-4-thio-pseudouridine (mls4qj), 4-thio-l-methyl-pseudouridine, 3-methyl-pseudouridine (m3ip), 2-thio-l-methyl-pseudouridine, 1-methyl-l-deaza- pseudouridine, 2-thio-l-methyl-l-deaza-pseudouridine, dihydrouridine (D), dihydropseudouridine, 5,6- dihydrouridine, 5-methyl-dihydrouridine (m5D), 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxy- uridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, Nl-methyl- pseudouridine, 3-(3-amino-3-carboxypropyl)uridine (acp3U), l-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp3 qi), 5-(isopentenylaminomethyl)uridine (inm5U), 5-(isopentenylaminomethyl)-2-thio-uridine (inm5s2U), a- thio-uridine, 2'-O-methyl-uridine (Um), 5,2'-O-dimethyl-uridine (m5Um), 2'-O-methyl-pseudouridine (qjm), 2-thio- 2'-O-methyl-uridine (s2Um), 5-methoxycarbonylmethyl-2'-O-methyl-uridine (mcm5Um), 5-carbamoylmethyl-2'-O- methyl-uridine (ncm5Um), 5-carboxymethylaminomethyl-2'-O-methyl-uridine (cmnmSUm), 3,2'-O-dimethyl- uridine (m3Um), 5-(isopentenylaminomethyl)-2'-O-methyl-uridine (inm5Um), 1-thio-uridine, deoxythymidine, 2'- F-ara-uridine, 2'-F-uridine, 2'-OH-ara-uridine, 5-(2-carbomethoxyvinyl) uridine, 5-[3-(l-E-propenylamino)uridine, or any other modified uridine known in the art.

[00892] In one embodiment, the RNA comprises other modified nucleosides or comprises further modified nucleosides, e.g., modified cytidine. For example, in one embodiment, in the RNA 5-methylcytidine is substituted partially or completely, preferably completely, for cytidine. In one embodiment, the RNA comprises 5- methylcytidine and one or more selected from pseudouridine (qj), Nl-methyl-pseudouridine (mlqj), and 5-methyl- uridine (m5U). In one embodiment, the RNA comprises 5-methylcytidine and Nl-methyl-pseudouridine (mlqj). In some embodiments, the RNA comprises 5-methylcytidine in place of each cytidine and Nl-methyl-pseudouridine (mlqi) in place of each uridine.

5' Caps

[00893] In some embodiments, an RNA described herein comprises a 5' cap. Natural eukaryotic mRNA comprises a 7-methylguanosine cap linked to the mRNA via a 5 ' to 5 '-triphosphate bridge resulting in capO structure (m7GpppN). In most eukaryotic mRNA and some viral mRNA, further modifications can occur at the 2'- hydroxy-group (2'-0H) (e.g., the 2'-hydroxyl group may be methylated to form 2'-O-Me) of the first and subsequent nucleotides producing "capl" and "cap2" five-prime ends, respectively). Diamond, et al., (2014) Cytokine & growth Factor Reviews, 25:543-550 reported that capO-mRNA cannot be translated as efficiently as capl-mRNA in which the role of 2'-O-Me in the penultimate position at the mRNA 5' end is determinant. Lack of the 2'-O-met has been shown to trigger innate immunity and activate IFN response. Daffis, et al. (2010) Nature, 468:452-456; and Zust et al. (2011) Nature Immunology, 12:137-143.

[00894] RNA capping is well researched and is described, e.g., in Decroly E et al. (2012) Nature Reviews 10: 51-65; and in Ramanathan A. et al., (2016) Nucleic Acids Res; 44(16): 7511-7526, the entire contents of each of which is hereby incorporated by reference. For example, in some embodiments, a 5'-cap structure which may be suitable in the context of the present invention is a capO (methylation of the first nucleobase, e.g. m7GpppN), capl (additional methylation of the ribose of the adjacent nucleotide of m7GpppN), cap2 (additional methylation of the ribose of the 2nd nucleotide downstream of the m7GpppN), cap3 (additional methylation of the ribose of the 3rd nucleotide downstream of the m7GpppN), cap4 (additional methylation of the ribose of the 4th nucleotide downstream of the m7GpppN), ARCA ("anti-reverse cap analogue"), modified ARCA (e.g. phosphothioate modified ARCA), inosine, N1 -methyl-guanosine, 2'-fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2- amino-guanosine, LNA-guanosine, and 2-azido-guanosine.

[00895] The term "5'-cap" as used herein refers to a structure found on the 5'-end of an RNA, e.g., mRNA, and generally includes a guanosine nucleotide connected to an RNA, e.g., mRNA, via a 5¹- to 5'-triphosphate linkage (also referred to as Gppp or G(5')ppp(5')). In some embodiments, a guanosine nucleoside included in a 5' cap may be modified, for example, by methylation at one or more positions (e.g., at the 7-position) on a base (guanine), and/or by methylation at one or more positions of a ribose. In some embodiments, a guanosine nucleoside included in a 5' cap comprises a 3'0 methylation at a ribose (3'0MeG). In some embodiments, a guanosine nucleoside included in a 5' cap comprises methylation at the 7-position of guanine (m7G). In some embodiments, a guanosine nucleoside included in a 5' cap comprises methylation at the 7-position of guanine and a 3' O methylation at a ribose (m7(3'OMeG)). It will be understood that the notation used in the above paragraph, e.g., "(m27,3'-O)G" or "m7(3'OMeG)", applies to other structures described herein.

[00896] In some embodiments, providing an RNA with a 5'-cap disclosed herein may be achieved by in vitro transcription, in which a 5'-cap is co-transcriptionally expressed into an RNA strand, or may be attached to an RNA post-transcriptionally using capping enzymes. In some embodiments, co-transcriptional capping with a cap disclosed improves the capping efficiency of an RNA compared to co-transcriptional capping with an appropriate reference comparator. In some embodiments, improving capping efficiency can increase a translation efficiency and/or translation rate of an RNA, and/or increase expression of an encoded polypeptide. In some embodiments, alterations to polynucleotides generates a non-hydrolyzable cap structure which can, for example, prevent decapping and increase RNA half-life.

[00897] In some embodiments, T7 RNA polymerase prefers G as the initial site. Accordingly, in some such embodiments, the present disclosure provides caps (e.g., trinucleotide and tetranucleotide caps described herein) wherein the 3'end of the trinucleotide (e.g., N2) or tetranucleotide cap (e.g.., N3) is G.

[00898] In some embodiments, it will be appreciated that all compounds or structures (e.g., 5' caps) provided herein encompass the free base or salt form (e.g., an Na+ salt) comprising a suitable counterion (e.g., Na+). Compounds or structures (e.g., 5' caps) depicted as a salt also encompass the free base and include suitable counterions (e.g., Na+).

[00899] In some embodiments, a utilized 5' caps is a capO, a capl, or cap2 structure. See, e.g., Fig. 1 of Ramanathan A et al., and Fig. 1 of Decroly E et al., each of which is incorporated herein by reference in its entirety. See, e.g., Fig. 1 of Ramanathan A et al., and Fig. 1 of Decroly E et al., each of which is incorporated herein by reference in its entirety. In some embodiments, an RNA described herein comprises a capl structure. In some embodiments, an RNA described herein comprises a cap2.

[00900] In some embodiments, an RNA described herein comprises a capO structure. In some embodiments, a capO structure comprises a guanosine nucleoside methylated at the 7-position of guanine ((m7)G). In some embodiments, such a capO structure is connected to an RNA via a 5¹- to 5 ’-tri phosphate linkage and is also referred to herein as (m7)Gppp. In some embodiments, a capO structure comprises a guanosine nucleoside methylated at the 2'-position of the ribose of guanosine In some embodiments, a capO structure comprises a guanosine nucleoside methylated at the 3'-position of the ribose of guanosine . In some embodiments, a guanosine nucleoside included in a 5' cap comprises methylation at the 7-position of guanine and at the 2'-position of the ribose ((m27,2'-O)G). In some embodiments, a guanosine nucleoside included in a 5' cap comprises methylation at the 7-position of guanine and at the 2'-position of the ribose ((m27,3'-O)G).

[00901] In some embodiments, a capl structure comprises a guanosine nucleoside methylated at the 7- position of guanine ((m7)G) and optionally methylated at the 2' or 3' position pf the ribose, and a 2'0 methylated first nucleotide in an RNA ((m2'-0)Nl). In some embodiments, a capl structure comprises a guanosine nucleoside methylated at the 7-position of guanine ((m7)G) and the 3' position of the ribose, and a 2'0 methylated first nucleotide in an RNA ((m2'-0)Nl). In some embodiments, a capl structure is connected to an RNA via a 5'- to 5'-triphosphate linkage and is also referred to herein as, e.g., ((m7)Gppp(2'-O)Nl) or (m27,3 - 0)Gppp(2'-0)Nl), wherein N1 is as defined and described herein. In some embodiments, a capl structure comprises a second nucleotide, N2, which is at position 2 and is chosen from A, G, C, or U, e.g., (m7)Gppp(2‘- 0)NlpN2 or (m27,3'-O)Gppp(2'-O)NlpN2 , wherein each of N1 and N2 is as defined and described herein.

[00902] In some embodiments, a cap2 structure comprises a guanosine nucleoside methylated at the 7- position of guanine ((m7)G) and optionally methylated at the 2' or 3' position of the ribose, and a 2'0 methylated first and second nucleotides in an RNA ((m2'-O)Nlp(m2'-O)N2). In some embodiments, a cap2 structure comprises a guanosine nucleoside methylated at the 7-position of guanine ((m7)G) and the 3' position of the ribose, and a 2'0 methylated first and second nucleotide in an RNA. In some embodiments, a cap2 structure is connected to an RNA via a 5'- to 5'-triphosphate linkage and is also referred to herein as, e.g., ((m7)Gppp(2‘- O)Nlp(2'-O)N2) or (m27,3'-O)Gppp(2'-O)Nlp(2'-O)N2), wherein each of N1 and N2 is as defined and described herein.

[00903] In some embodiments, the 5' cap is a dinucleotide cap structure. In some embodiments, the 5' cap is a dinucleotide cap structure comprising Nl, wherein N1 is as defined and described herein. In some embodiments, the 5' cap is a dinucleotide cap G*N1, wherein Nl is as defined above and herein, and: [00904] G* comprises a structure of formula (I):

a. (I) or a salt thereof, wherein each R2 and R3 is -OH or -0CH3; and

X is O or S.

[00905] In some embodiments, R2 is -OH. In some embodiments, R2 is -0CH3. In some embodiments, R3 is -OH. In some embodiments, R3 is -0CH3. In some embodiments, R2 is -OH and R3 is -OH. In some embodiments, R2 is -OH and R3 is -CH3. In some embodiments, R2 is -CH3 and R3 is -OH. In some embodiments, R2 is -CH3 and R3 is -CH3.

[00906] In some embodiments, X is O. In some embodiments, X is S.

[00907] In some embodiments, the 5' cap is a dinucleotide capO structure (e.g., (m7)GpppNl, (m27,2'-

O)GpppNl, (m27,3'-O)GpppNl, (m7)GppSpNl, (m27,2'-O)GppSpNl, or (m27,3'-O)GppSpNl), wherein Nl is as defined and described herein. In some embodiments, the 5' cap is a dinucleotide capO structure (e.g., (m7)GpppNl, (m27,2'-O)GpppNl, (m27,3'-O)GpppNl, (m7)GppSpNl, (m27,2'-O)GppSpNl, or (m27,3'- OJGppSpNl), wherein N1 is G. In some embodiments, the 5' cap is a dinucleotide capO structure (e.g., (m7)GpppNl, (m27,2'-O)GpppNl, (m27,3'-O)GpppNl, (m7)GppSpNl, (m27,2'-O)GppSpNl, or (m27,3'- O)GppSpNl), wherein N1 is A, U, or C. In some embodiments, the 5' cap is a dinucleotide capl structure (e.g., (m7)Gppp(m2'-O)Nl, (m27,2'-O)Gppp(m2'-O)Nl, (m27,3'-O)Gppp(m2'-O)Nl, (m7)GppSp(m2'-O)Nl, (m27,2'- 0)GppSp(m2'-0)Nl, or (m27,3'-O)GppSp(m2'-O)Nl), wherein N1 is as defined and described herein. In some embodiments, the 5' cap is selected from the group consisting of (m7)GpppG ("EcapO"), (m7)Gppp(m2'-O)G ("Ecapl"), (m27,3'-O)GpppG ("ARCA" or "DI"), and (m27,2'-O)GppSpG ("beta-S-ARCA"). In some embodiments, the 5' cap is (m7)GpppG ("EcapO"), having a structure:

or a salt thereof.

[00908] In some embodiments, the 5' cap is (m7)Gppp(m2'-O)G ("Ecapl"), having a structure:

or a salt thereof.

[00909] In some embodiments, the 5' cap is (m27,3'-O)GpppG ("ARCA" or "DI"), having a structure:

or a salt thereof.

[00910] In some embodiments, the 5' cap is (m27,2'-O)GppSpG ("beta-S-ARCA"), having a structure:

or a salt thereof. [00911] In some embodiments, the 5' cap is a trinucleotide cap structure. In some embodiments, the 5' cap is a trinucleotide cap structure comprising NlpN2, wherein N1 and N2 are as defined and described herein. In some embodiments, the 5' cap is a trinucleotide cap G*NlpN2, wherein N1 and N2 are as defined above and herein, and:

[00912] G* comprises a structure of formula (I):

b. (I) or a salt thereof, wherein R2, R3, and X are as defined and described herein.

[00913] In some embodiments, the 5' cap is a trinucleotide capO structure (e.g. (m7)GpppNlpN2, (m27,2'-

0)GpppNlpN2, or (m27,3'-O)GpppNlpN2), wherein N1 and N2 are as defined and described herein). In some embodiments, the 5' cap is a trinucleotide capl structure (e.g., (m7)Gppp(m2'-O)NlpN2, (m27,2'-O)Gppp(m2'- 0)NlpN2, (m27,3'-O)Gppp(m2'-O)NlpN2), wherein N1 and N2 are as defined and described herein. In some embodiments, the 5' cap is a trinucleotide cap2 structure (e.g., (m7)Gppp(m2'-O)Nlp(m2'-O)N2, (m27,2 - O)Gppp(m2'-O)Nlp(m2'-O)N2, (m27,3'-O)Gppp(m2'-O)Nlp(m2'-O)N2), wherein N1 and N2 are as defined and described herein. In some embodiments, the 5' cap is selected from the group consisting of (m27,3 - 0)Gppp(m2'-0)ApG ("CleanCap AG 3' OMe", "CC413"), (m27,3'-O)Gppp(m2'-O)GpG ("CleanCap GG"), (m7)Gppp(m2'-O)ApG, (m7)Gppp(m2'-O)GpG, (m27,3'-O)Gppp(m26,2'-O)ApG, and (m7)Gppp(m2'-O)ApU. In some embodiments, the 5' cap is selected from the group consisting of (m27,3'-O)Gppp(m2'-O)ApG ("CleanCap AG", "CC413"), (m27,3'-O)Gppp(m2'-O)GpG ("CleanCap GG"), (m7)Gppp(m2'-O)ApG, and (m27,3'- O)Gppp(m26,2'-O)ApG, (m7)Gppp(m2'-O)ApU, and (m27,3'-O)Gppp(m2'-O)CpG.

[00914] In some embodiments, the 5' cap is (m27,3'-O)Gppp(m2'-O)ApG ("CleanCap AG 3' OMe", "CC413"), having a structure:

or a salt thereof.

[00915] In some embodiments, the 5' cap is (m27,3'-O)Gppp(m2'-O)GpG ("CleanCap GG"), having a structure:

[00916] In some embodiments, the 5' cap is (m7)Gppp(m2'-O)ApG, having a structure:

or a salt thereof.

[00917] In some embodiments, the 5' cap is (m7)Gppp(m2'-O)GpG, having a structure:

or a salt thereof.

[00918] In some embodiments, the 5' cap is (m27,3'-O)Gppp(m26,2'-O)ApG, having a structure:

or a salt thereof.

[00919] In some embodiments, the 5' cap is (m7)Gppp(m2'-O)ApU, having a structure:

or a salt thereof.

[00920] In some embodiments, the 5' cap is (m27,3'-O)Gppp(m2'-O)CpG, having a structure:

or a salt thereof.

[00921] In some embodiments, the 5' cap is a tetranucleotide cap structure. In some embodiments, the 5' cap is a tetranucleotide cap structure comprising NlpN2pN3, wherein Nl, N2, and N3 are as defined and described herein. In some embodiments, the 5' cap is a tetranucleotide cap G*NlpN2pN3, wherein Nl, N2, and

N3 are as defined above and herein, and:

[00922] G* comprises a structure of formula (I):

c. (I)

[00923] or a salt thereof, wherein R2, R3, and X are as defined and described herein.

[00924] In some embodiments, the 5' cap is a tetranucleotide capO structure (e.g. (m7)GpppNlpN2pN3,

(m27,2'-O)GpppNlpN2pN3, or (m27,3'-O)GpppNlN2pN3), wherein Nl, N2, and N3 are as defined and described herein). In some embodiments, the 5' cap is a tetranucleotide Capl structure (e.g., (m7)Gppp(m2'-O)NlpN2pN3, (m27,2'-O)Gppp(m2'-O)NlpN2pN3, (m27,3'-O)Gppp(m2'-O)NlpN2N3), wherein Nl, N2, and N3 are as defined and described herein. In some embodiments, the 5' cap is a tetranucleotide Cap2 structure (e.g., (m7)Gppp(m2'- O)Nlp(m2'-O)N2pN3, (m27,2'-O)Gppp(m2'-O)Nlp(m2'-O)N2pN3, (m27,3'-O)Gppp(m2'-O)Nlp(m2'-O)N2pN3), wherein Nl, N2, and N3 are as defined and described herein. In some embodiments, the 5' cap is selected from the group consisting of (m27,3'-O)Gppp(m2'-O)Ap(m2'-O)GpG, (m27,3'-O)Gppp(m2'-O)Gp(m2'-O)GpC, (m7)Gppp(m2'-O)Ap(m2'-O)UpA, and (m7)Gppp(m2'-O)Ap(m2'-O)GpG.

[00925] In some embodiments, the 5' cap is (m27,3'-O)Gppp(m2'-O)Ap(m2'-O)GpG, having a structure:

or a salt thereof.

[00926] In some embodiments, the 5' cap is (m27,3'-O)Gppp(m2'-O)Gp(m2'-O)GpC, having a structure:

or a salt thereof.

[00927] In some embodiments, the 5' cap is (m7)Gppp(m2'-O)Ap(m2'-O)UpA, having a structure:

or a salt thereof.

[00928] In some embodiments, the 5' cap is (m7)Gppp(m2'-O)Ap(m2'-O)GpG, having a structure:

or a salt thereof.

[00929] A particularly preferred cap is beta-S-ARCA(Dl) (m27,2'-OGppSpG) or m27,3'-OGppp(ml2'-O)ApG.

[00930] In some embodiments, RNA according to the present disclosure comprises a 5'-UTR and/or a 3'-

UTR. The term "untranslated region" or "UTR" relates to a region in a DNA molecule which is transcribed but is not translated into an amino acid sequence, or to the corresponding region in an RNA molecule, such as an mRNA molecule. An untranslated region (UTR) can be present 5' (upstream) of an open reading frame (5'-UTR) and/or 3' (downstream) of an open reading frame (3'-UTR). A 5'-UTR, if present, is located at the 5' end, upstream of the start codon of a protein-encoding region. A 5'-UTR is downstream of the 5'-cap (if present), e.g. directly adjacent to the 5'-cap. A 3'-UTR, if present, is located at the 3' end, downstream of the termination codon of a protein-encoding region, but the term "3'-UTR" does preferably not include the poly(A) sequence. Thus, the 3'- UTR is upstream of the poly(A) sequence (if present), e.g. directly adjacent to the poly(A) sequence.

[00931] In some embodiments, RNA comprises a 5'-UTR comprising the nucleotide sequence of SEQ ID NO:

12, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 12.

[00932] In some embodiments, RNA comprises a 3'-UTR comprising the nucleotide sequence of SEQ ID NO:

13, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 13. In some embodiments, RNA comprises a 3'-UTR comprising the nucleotide sequence of SEQ ID NO: 601, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 601. In some embodiments, RNA comprises a 3'-UTR comprising the nucleotide sequence of SEQ ID NO: 602, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 602. [00933] A particularly preferred 5'-UTR comprises the nucleotide sequence of SEQ ID NO: 12. A particularly preferred 3'-UTR comprises the nucleotide sequence of SEQ ID NO: 13.

[00934] In some embodiments, the RNA according to the present disclosure comprises a 3'-poly(A) sequence.

[00935] As used herein, the term "poly(A) sequence" or "poly-A tail" refers to an uninterrupted or interrupted sequence of adenylate residues which is typically located at the 3'-end of an RNA molecule. Poly(A) sequences are known to those of skill in the art and may follow the 3'-UTR in the RNAs described herein. An uninterrupted poly(A) sequence is characterized by consecutive adenylate residues. In nature, an uninterrupted poly(A) sequence is typical. RNAs disclosed herein can have a poly(A) sequence attached to the free 3'-end of the RNA by a template-independent RNA polymerase after transcription or a poly(A) sequence encoded by DNA and transcribed by a template-dependent RNA polymerase.

[00936] It has been demonstrated that a poly(A) sequence of about 120 A nucleotides has a beneficial influence on the levels of RNA in transfected eukaryotic cells, as well as on the levels of protein that is translated from an open reading frame that is present upstream (S') of the poly(A) sequence (Holtkamp et al., 2006, Blood, vol. 108, pp. 4009-4017).

[00937] The poly(A) sequence may be of any length. In some embodiments, a poly(A) sequence comprises, essentially consists of, or consists of at least 20, at least 30, at least 40, at least 80, or at least 100 and up to 500, up to 400, up to 300, up to 200, or up to 150 A nucleotides, and, in particular, about 120 A nucleotides. In this context, "essentially consists of" means that most nucleotides in the poly(A) sequence, typically at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% by number of nucleotides in the poly(A) sequence are A nucleotides, but permits that remaining nucleotides are nucleotides other than A nucleotides, such as U nucleotides (uridylate), G nucleotides (guanylate), or C nucleotides (cytidylate). In this context, "consists of" means that all nucleotides in the poly(A) sequence, i.e., 100% by number of nucleotides in the poly(A) sequence, are A nucleotides. The term "A nucleotide" or "A" refers to adenylate.

[00938] In some embodiments, a poly(A) sequence is attached during RNA transcription, e.g., during preparation of in vitro transcribed RNA, based on a DNA template comprising repeated dT nucleotides (deoxythymidylate) in the strand complementary to the coding strand. The DNA sequence encoding a poly(A) sequence (coding strand) is referred to as poly(A) cassette.

[00939] In some embodiments, the poly(A) cassette present in the coding strand of DNA essentially consists of dA nucleotides, but is interrupted by a random sequence of the four nucleotides (dA, dC, dG, and dT). Such random sequence may be 5 to 50, 10 to 30, or 10 to 20 nucleotides in length. Such a cassette is disclosed in WO 2016/005324 Al, hereby incorporated by reference. Any poly(A) cassette disclosed in WO 2016/005324 Al may be used in the present disclosure. A poly(A) cassette that essentially consists of dA nucleotides, but is interrupted by a random sequence having an equal distribution of the four nucleotides (dA, dC, dG, dT) and having a length of e.g., 5 to 50 nucleotides shows, on DNA level, constant propagation of plasmid DNA in E. coli and is still associated, on RNA level, with the beneficial properties with respect to supporting RNA stability and translational efficiency is encompassed. Consequently, in some embodiments, the poly(A) sequence contained in an RNA molecule described herein essentially consists of A nucleotides, but is interrupted by a random sequence of the four nucleotides (A, C, G, U). Such random sequence may be 5 to 50, 10 to 30, or 10 to 20 nucleotides in length. [00940] In some embodiments, no nucleotides other than A nucleotides flank a poly(A) sequence at its 3'- end, i.e., the poly(A) sequence is not masked or followed at its 3'-end by a nucleotide other than A.

[00941] In some embodiments, the poly(A) sequence may comprise at least 20, at least 30, at least 40, at least 80, or at least 100 and up to 500, up to 400, up to 300, up to 200, or up to 150 nucleotides. In some embodiments, the poly(A) sequence may essentially consist of at least 20, at least 30, at least 40, at least 80, or at least 100 and up to 500, up to 400, up to 300, up to 200, or up to 150 nucleotides. In some embodiments, the poly(A) sequence may consist of at least 20, at least 30, at least 40, at least 80, or at least 100 and up to 500, up to 400, up to 300, up to 200, or up to 150 nucleotides. In some embodiments, the poly(A) sequence comprises at least 100 nucleotides. In some embodiments, the poly(A) sequence comprises about 150 nucleotides. In some embodiments, the poly(A) sequence comprises about 120 nucleotides. [00942] In some embodiments, a poly(A) sequence included in an RNA described herein is a interrupted poly(A) sequence, e.g., as described in W02016/005324, the entire content of which is incorporated herein by reference for purposes described herein. In some embodiments, a poly(A) sequence comprises a stretch of at least 20 adenosine residues (including, e.g., at least 30, at least 40, at least 50, at least 60, at least 70, or more adenosine residues), followed by a linker sequence (e.g., in some embodiments comprising non-A nucleotides) and another stretch of at least 20 adenosine residues (including, e.g., at least 30, at least 40, at least 50, at least 60, at least 70, or more adenosine residues). In some embodiments, such a linker sequence may be 3-50 nucleotides in length, or 5-25 nucleotides in length, or 10-15 nucleotides in length. In some embodiments, a poly(A) sequence comprises a stretch of about 30 adenosine residues, followed by a linker sequence having a length of about 5-15 nucleoties (e.g., in some embodiments comprising non-A nucleotides) and another stretch of about 70 adenosine residues.

[00943] In some embodiments, RNA comprises a poly(A) sequence comprising the nucleotide sequence of SEQ ID NO: 14, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 14.

[00944] A particularly preferred poly(A) sequence comprises the nucleotide sequence of SEQ ID NO: 14. [00945] According to the present disclosure, vaccine antigen is preferably administered as single-stranded, 5'-capped RNA (e.g., mRNA) that is translated into the respective protein upon entering cells of a subject being administered the RNA. Preferably, the RNA contains structural elements optimized for maximal efficacy of the RNA with respect to stability and translational efficiency (5'-cap, 5'-UTR, 3'-UTR, poly(A) sequence).

[00946] In one embodiment, beta-S-ARCA(Dl) is utilized as specific capping structure at the 5'-end of the RNA. In one embodiment, m27,3'-OGppp(ml2'-O)ApG is utilized as specific capping structure at the 5'-end of the RNA. In one embodiment, the 5'-UTR sequence is derived from the human alpha-globin mRNA and optionally has an optimized 'Kozak sequence' to increase translational efficiency. In one embodiment, a combination of two sequence elements (FI element) derived from the "amino terminal enhancer of split" (AES) mRNA (called F) and the mitochondrial encoded 12S ribosomal RNA (called I) are placed between the coding sequence and the poly(A) sequence to assure higher maximum protein levels and prolonged persistence of the RNA (e.g., mRNA). In one embodiment, two re-iterated 3’-UTRs derived from the human beta-globin mRNA are placed between the coding sequence and the poly(A) sequence to assure higher maximum protein levels and prolonged persistence of the RNA (e.g., mRNA). In one embodiment, a poly(A) sequence measuring 110 nucleotides in length, consisting of a stretch of 30 adenosine residues, followed by a linker sequence (e.g., 10 nucleotide linker sequence) and another 70 adenosine residues is used. This poly(A) sequence was designed to enhance RNA stability and translational efficiency.

[00947] In one embodiment of all aspects of the present disclosure, RNA encoding a vaccine antigen is expressed in cells of the subject treated to provide the vaccine antigen. In one embodiment of all aspects of the present disclosure, the RNA is transiently expressed in cells of the subject. In one embodiment of all aspects of the present disclosure, the RNA is in vitro transcribed RNA. In one embodiment of all aspects of the present disclosure, expression of the vaccine antigen is at the cell surface. In one embodiment of all aspects of the present disclosure, the vaccine antigen is expressed and presented in the context of MHC. In one embodiment of all aspects of the present disclosure, expression of the vaccine antigen is into the extracellular space, i.e., the vaccine antigen is secreted.

[00948] In the context of the present disclosure, the term "transcription" relates to a process, wherein the genetic code in a DNA sequence is transcribed into RNA. Subsequently, the RNA may be translated into peptide or protein. [00949] According to the present disclosure, the term "transcription" comprises "in vitro transcription", wherein the term "in vitro transcription" relates to a process wherein RNA, in particular mRNA, is in vitro synthesized in a cell-free system, preferably using appropriate cell extracts. Preferably, cloning vectors are applied for the generation of transcripts. These cloning vectors are generally designated as transcription vectors and are according to the present disclosure encompassed by the term "vector". According to the present disclosure, the RNA used in the present disclosure preferably is in vitro transcribed RNA (IVT-RNA) and may be obtained by in vitro transcription of an appropriate DNA template. The promoter for controlling transcription can be any promoter for any RNA polymerase. Particular examples of RNA polymerases are the T7, T3, and SP6 RNA polymerases. Preferably, the in vitro transcription according to the disclosure is controlled by a T7 or SP6 promoter. A DNA template for in vitro transcription may be obtained by cloning of a nucleic acid, in particular cDNA, and introducing it into an appropriate vector for in vitro transcription. The cDNA may be obtained by reverse transcription of RNA.

[00950] With respect to RNA, the term "expression" or "translation" relates to the process in the ribosomes of a cell by which a strand of mRNA directs the assembly of a sequence of amino acids to make a peptide or protein.

[00951] In one embodiment, after administration of the RNA described herein, e.g., formulated as RNA lipid particles, at least a portion of the RNA is delivered to a target cell. In one embodiment, at least a portion of the RNA is delivered to the cytosol of the target cell. In one embodiment, the RNA is translated by the target cell to produce the peptide or protein it encodes. In one embodiment, the target cell is a spleen cell. In one embodiment, the target cell is an antigen presenting cell such as a professional antigen presenting cell in the spleen. In one embodiment, the target cell is a dendritic cell or macrophage. RNA particles such as RNA lipid particles described herein may be used for delivering RNA to such target cell. Accordingly, the present disclosure also relates to a method for delivering RNA to a target cell in a subject comprising the administration of the RNA particles described herein to the subject. In one embodiment, the RNA is delivered to the cytosol of the target cell. In one embodiment, the RNA is translated by the target cell to produce the peptide or protein encoded by the RNA.

[00952] "Encoding" refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.

[00953] In one embodiment, the RNA encoding vaccine antigen to be administered according to the present disclosure is non-immunogenic. RNA encoding immunostimulant may be administered according to the present disclosure to provide an adjuvant effect. The RNA encoding immunostimulant may be standard RNA or non- immunogenic RNA.

[00954] The term "non-immunogenic RNA" as used herein refers to RNA that does not induce a response by the immune system upon administration, e.g., to a mammal, or induces a weaker response than would have been induced by the same RNA that differs only in that it has not been subjected to the modifications and treatments that render the non-immunogenic RNA non-immunogenic, i.e., than would have been induced by standard RNA (stdRNA). In one preferred embodiment, non-immunogenic RNA, which is also termed modified RNA (modRNA) herein, is rendered non-immunogenic by incorporating modified nucleosides suppressing RNA-mediated activation of innate immune receptors into the RNA and removing double-stranded RNA (dsRNA).

[00955] For rendering the non-immunogenic RNA non-immunogenic by the incorporation of modified nucleosides, any modified nucleoside may be used as long as it lowers or suppresses immunogenicity of the RNA. Particularly preferred are modified nucleosides that suppress RNA-mediated activation of innate immune receptors. In one embodiment, the modified nucleosides comprises a replacement of one or more uridines with a nucleoside comprising a modified nucleobase. In one embodiment, the modified nucleobase is a modified uracil. In one embodiment, the nucleoside comprising a modified nucleobase is selected from the group consisting of 3- methyl-uridine (m3U), 5-methoxy-uridine (mo5U), 5-aza-uridine, 6-aza-uridine, 2-thio-5-aza-uridine, 2-thio- uridine (s2U), 4-thio-uridine (s4U), 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxy-uridine (ho5U), 5- aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridine or 5-bromo-uridine), uridine 5-oxyacetic acid (cmo5U), uridine 5-oxyacetic acid methyl ester (mcmo5U), 5-carboxymethyl-uridine (cm5U), 1-carboxymethyl- pseudouridine, 5-carboxyhydroxymethyl-uridine (chm5U), 5-carboxyhydroxymethyl-uridine methyl ester (mchm5U), 5-methoxycarbonylmethyl-uridine (mcm5U), 5-methoxycarbonylmethyl-2-thio-uridine (mcm5s2U), 5- aminomethyl-2-thio-uridine (nm5s2U), 5-methylaminomethyl-uridine (mnm5U), 1-ethyl-pseudouridine, 5- methylaminomethyl-2-thio-uridine (mnm5s2U), 5-methylaminomethyl-2-seleno-uridine (mnm5se2U), 5- carbamoylmethyl-uridine (ncm5U), 5-carboxymethylaminomethyl-uridine (cmnm5U), 5- carboxymethylaminomethyl-2-thio-uridine (cmnm5s2U), 5-propynyl-uridine, 1-propynyl-pseudouridine, 5- taurinomethyl-uridine (Tm5U), 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine(Tm5s2U), 1- taurinomethyl-4-thio-pseudouridine), 5-methyl-2-thio-uridine (m5s2U), l-methyl-4-thio-pseudouridine (mls4qi), 4-thio-l-methyl-pseudouridine, 3-methyl-pseudouridine (m3qi), 2-thio-l-methyl-pseudouridine, 1-methyl-l-deaza- pseudouridine, 2-thio-l-methyl-l-deaza-pseudouridine, dihydrouridine (D), dihydropseudouridine, 5,6- dihydrouridine, 5-methyl-dihydrouridine (m5D), 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxy- uridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, Nl-methyl- pseudouridine, 3-(3-amino-3-carboxypropyl)uridine (acp3U), l-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp3 ip), 5-(isopentenylaminomethyl)uridine (inm5U), 5-(isopentenylaminomethyl)-2-thio-uridine (inm5s2U), o- thio-uridine, 2'-0-methyl-uridine (Um), 5,2'-O-dimethyl-uridine (m5Um), 2'-O-methyl-pseudouridine (ipm), 2-thio- 2'-0-methyl-uridine (s2Um), 5-methoxycarbonylmethyl-2'-O-methyl-uridine (mcm5Um), 5-carbamoylmethyl-2'-O- methyl-uridine (ncm5Um), 5-carboxymethylaminomethyl-2'-O-methyl-uridine (cmnm5Um), 3,2'-O-dimethyl- uridine (m3Um), 5-(isopentenylaminomethyl)-2'-O-methyl-uridine (inmSUm), 1-thio-uridine, deoxythymidine, 2'- F-ara-uridine, 2'-F-uridine, 2'-0H-ara-uridine, 5-(2-carbomethoxyvinyl) uridine, and 5-[3-(l-E- propenylamino)uridine. In one particularly preferred embodiment, the nucleoside comprising a modified nucleobase is pseudouridine (ip), Nl-methyl-pseudouridine (mlip) or 5-methyl-uridine (m5U), in particular Nl- methyl-pseudouridine.

[00956] In one embodiment, the replacement of one or more uridines with a nucleoside comprising a modified nucleobase comprises a replacement of at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 25%, at least 50%, at least 75%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% of the uridines.

[00957] During synthesis of RNA (e.g., mRNA) by in vitro transcription (IVT) using T7 RNA polymerase significant amounts of aberrant products, including double-stranded RNA (dsRNA) are produced due to unconventional activity of the enzyme. dsRNA induces inflammatory cytokines and activates effector enzymes leading to protein synthesis inhibition. dsRNA can be removed from RNA such as IVT RNA, for example, by ionpair reversed phase HPLC using a non-porous or porous C-18 polystyrene-divinylbenzene (PS-DVB) matrix. Alternatively, an enzymatic based method using E. coli RNaselll that specifically hydrolyzes dsRNA but not ssRNA, thereby eliminating dsRNA contaminants from IVT RNA preparations can be used. Furthermore, dsRNA can be separated from ssRNA by using a cellulose material. In one embodiment, an RNA preparation is contacted with a cellulose material and the ssRNA is separated from the cellulose material under conditions which allow binding of dsRNA to the cellulose material and do not allow binding of ssRNA to the cellulose material.

[00958] As the term is used herein, "remove" or "removal" refers to the characteristic of a population of first substances, such as non-immunogenic RNA, being separated from the proximity of a population of second substances, such as dsRNA, wherein the population of first substances is not necessarily devoid of the second substance, and the population of second substances is not necessarily devoid of the first substance. However, a population of first substances characterized by the removal of a population of second substances has a measurably lower content of second substances as compared to the non-separated mixture of first and second substances.

[00959] In one embodiment, the removal of dsRNA from non-immunogenic RNA comprises a removal of dsRNA such that less than 10%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, less than 0.3%, or less than 0.1% of the RNA in the non-immunogenic RNA composition is dsRNA. In one embodiment, the non-immunogenic RNA is free or essentially free of dsRNA. In some embodiments, the non- immunogenic RNA composition comprises a purified preparation of single-stranded nucleoside modified RNA. For example, in some embodiments, the purified preparation of single-stranded nucleoside modified RNA is substantially free of double stranded RNA (dsRNA). In some embodiments, the purified preparation is at least 90%, at least 91%, at least 92%, at least 93 %, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or at least 99.9% single stranded nucleoside modified RNA, relative to all other nucleic acid molecules (DNA, dsRNA, etc.).

[00960] In one embodiment, the non-immunogenic RNA is translated in a cell more efficiently than standard RNA with the same sequence. In one embodiment, translation is enhanced by a factor of 2-fold relative to its unmodified counterpart. In one embodiment, translation is enhanced by a 3-fold factor. In one embodiment, translation is enhanced by a 4-fold factor. In one embodiment, translation is enhanced by a 5-fold factor. In one embodiment, translation is enhanced by a 6-fold factor. In one embodiment, translation is enhanced by a 7-fold factor. In one embodiment, translation is enhanced by an 8-fold factor. In one embodiment, translation is enhanced by a 9-fold factor. In one embodiment, translation is enhanced by a 10-fold factor. In one embodiment, translation is enhanced by a 15-fold factor. In one embodiment, translation is enhanced by a 20-fold factor. In one embodiment, translation is enhanced by a 50-fold factor. In one embodiment, translation is enhanced by a 100-fold factor. In one embodiment, translation is enhanced by a 200-fold factor. In one embodiment, translation is enhanced by a 500-fold factor. In one embodiment, translation is enhanced by a 1000-fold factor. In one embodiment, translation is enhanced by a 2000-fold factor. In one embodiment, the factor is 10-1000-fold. In one embodiment, the factor is 10-100-fold. In one embodiment, the factor is 10-200-fold. In one embodiment, the factor is 10-300-fold. In one embodiment, the factor is 10-500-fold. In one embodiment, the factor is 20- 1000-fold. In one embodiment, the factor is 30-1000-fold. In one embodiment, the factor is 50-1000-fold. In one embodiment, the factor is 100-1000-fold. In one embodiment, the factor is 200-1000-fold. In one embodiment, translation is enhanced by any other significant amount or range of amounts.

[00961] In one embodiment, the non-immunogenic RNA exhibits significantly less innate immunogenicity than standard RNA with the same sequence. In one embodiment, the non-immunogenic RNA exhibits an innate immune response that is 2-fold less than its unmodified counterpart. In one embodiment, innate immunogenicity is reduced by a 3-fold factor. In one embodiment, innate immunogenicity is reduced by a 4-fold factor. In one embodiment, innate immunogenicity is reduced by a 5-fold factor. In one embodiment, innate immunogenicity is reduced by a 6-fold factor. In one embodiment, innate immunogenicity is reduced by a 7-fold factor. In one embodiment, innate immunogenicity is reduced by a 8-fold factor. In one embodiment, innate immunogenicity is reduced by a 9-fold factor. In one embodiment, innate immunogenicity is reduced by a 10-fold factor. In one embodiment, innate immunogenicity is reduced by a 15-fold factor. In one embodiment, innate immunogenicity is reduced by a 20-fold factor. In one embodiment, innate immunogenicity is reduced by a 50-fold factor. In one embodiment, innate immunogenicity is reduced by a 100-fold factor. In one embodiment, innate immunogenicity is reduced by a 200-fold factor. In one embodiment, innate immunogenicity is reduced by a 500-fold factor. In one embodiment, innate immunogenicity is reduced by a 1000-fold factor. In one embodiment, innate immunogenicity is reduced by a 2000-fold factor.

[00962] The term "exhibits significantly less innate immunogenicity" refers to a detectable decrease in innate immunogenicity. In one embodiment, the term refers to a decrease such that an effective amount of the non- immunogenic RNA can be administered without triggering a detectable innate immune response. In one embodiment, the term refers to a decrease such that the non-immunogenic RNA can be repeatedly administered without eliciting an innate immune response sufficient to detectably reduce production of the protein encoded by the non-immunogenic RNA. In one embodiment, the decrease is such that the non-immunogenic RNA can be repeatedly administered without eliciting an innate immune response sufficient to eliminate detectable production of the protein encoded by the non-immunogenic RNA.

[00963] "Immunogenicity" is the ability of a foreign substance, such as RNA, to provoke an immune response in the body of a human or other animal. The innate immune system is the component of the immune system that is relatively unspecific and immediate. It is one of two main components of the vertebrate immune system, along with the adaptive immune system.

[00964] As used herein "endogenous" refers to any material from or produced inside an organism, cell, tissue or system.

[00965] As used herein, the term "exogenous" refers to any material introduced from or produced outside an organism, cell, tissue or system.

[00966] The term "expression" as used herein is defined as the transcription and/or translation of a particular nucleotide sequence.

[00967] As used herein, the terms "linked," "fused", or "fusion" are used interchangeably. These terms refer to the joining together of two or more elements or components or domains.

Codon-optimization / Increase in G/C content

[00968] In some embodiment, the amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof described herein is encoded by a coding sequence which is codon-optimized and/or the G/C content of which is increased compared to wild type coding sequence. This also includes embodiments, wherein one or more sequence regions of the coding sequence are codon-optimized and/or increased in the G/C content compared to the corresponding sequence regions of the wild type coding sequence. In one embodiment, the codon-optimization and/or the increase in the G/C content preferably does not change the sequence of the encoded amino acid sequence.

[00969] The term "codon-optimized" refers to the alteration of codons in the coding region of a nucleic acid molecule to reflect the typical codon usage of a host organism without preferably altering the amino acid sequence encoded by the nucleic acid molecule. Within the context of the present disclosure, coding regions are preferably codon-optimized for optimal expression in a subject to be treated using the RNA molecules described herein. Codon-optimization is based on the finding that the translation efficiency is also determined by a different frequency in the occurrence of tRNAs in cells. Thus, the sequence of RNA may be modified such that codons for which frequently occurring tRNAs are available are inserted in place of "rare codons".

[00970] In some embodiments of the present disclosure, the guanosine/cytosine (G/C) content of the coding region of the RNA described herein is increased compared to the G/C content of the corresponding coding sequence of the wild type RNA, wherein the amino acid sequence encoded by the RNA is preferably not modified compared to the amino acid sequence encoded by the wild type RNA. This modification of the RNA sequence is based on the fact that the sequence of any RNA region to be translated is important for efficient translation of that mRNA. Sequences having an increased G (guanosine)/C (cytosine) content are more stable than sequences having an increased A (adenosine)/U (uracil) content. In respect to the fact that several codons code for one and the same amino acid (so-called degeneration of the genetic code), the most favourable codons for the stability can be determined (so-called alternative codon usage). Depending on the amino acid to be encoded by the RNA, there are various possibilities for modification of the RNA sequence, compared to its wild type sequence. In particular, codons which contain A and/or U nucleotides can be modified by substituting these codons by other codons, which code for the same amino acids but contain no A and/or U or contain a lower content of A and/or U nucleotides.

[00971] In various embodiments, the G/C content of the coding region of the RNA described herein is increased by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 55%, or even more compared to the G/C content of the coding region of the wild type RNA. In some embodiments, G/C content of a coding region is increased by about 10% to about 60% (e.g., by about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, or by about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, or about 60%) compared to the G/C content of the coding region of the wild type RNA.

[00972] In some embodiments, RNA disclosed herein comprises a sequence disclosed herein (e.g., SEQ ID NO: 9), that has been modified to encode one or more mutations characteristic of a SARS-CoV-2 variant (e.g., ones described herein including but not limited to a BA.2, JN.l, KP.2, XEC, or a BA.4/5 Omicron variant). In some embodiments, RNA can be modified to encode one or more mutations characteristic of a SARS-CoV-2 variant by making as few nucleotide changes as possible. In some embodiments, RNA can be modified to encode one or more mutations that are characteristic of a SARS-CoV-2 variant by introducing mutations that result in high codon-optimization and/or increased G/C content.

[00973] In some embodiments, one or more mutations characteristic of a SARS-CoV-2 variant are introduced onto a full-length S protein (e.g., an S protein comprising SEQ ID NO: 1). In some embodiments one or more mutations characteristic of a SARS-CoV-2 variant are introduced onto a full-length S protein having one or more proline mutations that increase stability of a prefusion confirmation. For example, in some embodiments, proline substitutions are made at positions corresponding to positions 986 and 987 of SEQ ID NO: 1. In some embodiments, at least 4 proline substitutions are made. In some embodiments, at least four of such proline mutations include mutations at positions corresponding to residues 817, 892, 899, and 942 of SEQ ID NO: 1, e.g., as described in WO 2021243122 A2, the entire contents of which are incorporated herein by reference in its entirety. In some embodiments, such a SARS-CoV-2 S protein comprising proline substitutions at positions corresponding to residues 817, 892, 899, and 942 of SEQ ID NO: 1, may further comprise proline substitutions at positions corresponding to residues 986 and 987 of SEQ ID NO: 1. In some embodiments, one or more mutations characteristic of a SARS-CoV-2 variant are introduced onto an immunogenic fragment of an S protein (e.g., an RBD (e.g., the RBD region of SEQ ID NO: 1 or a corresponding region of an S protein of a SARS-CoV-2 variant), a truncated SI domain, and/or an S2 domain). Exemplary Embodiments of administered RNAs

[00974] In some embodiments, the present disclosure provides an RNA (e.g., mRNA) comprising an open reading frame encoding a polypeptide that comprises at least a portion of a SARS-CoV-2 S protein. The RNA is suitable for intracellular expression of the polypeptide. In some embodiments, such an encoded polypeptide comprises a sequence corresponding to the complete S protein. In some embodiments, such an encoded polypeptide does not comprise a sequence corresponding to the complete S protein. In some embodiments, the encoded polypeptide comprises a sequence that corresponds to the receptor binding domain (RBD). In some embodiments, the encoded polypeptide comprises a sequence that corresponds to the RBD, and further comprises a trimerization domain (e.g., a trimerization domain as disclosed herein, such as a fibritin domain). In some embodiments an RBD comprises a signaling domain (e.g., a signaling domain as disclosed herein). In some embodiments an RBD comprises a transmembrane domain (e.g., a transmembrane domain as disclosed herein). In some embodiments, an RBD comprises a signaling domain and a trimerization domain. In some embodiments, an RBD comprises a signaling domain, a trimerization domain, and transmembrane domain.

[00975] In some embodiments, the encoded polypeptide comprises a sequence that corresponds to two receptor binding domains. In some embodiments, the encoded polypeptide comprises a sequence that corresponds to two receptor binding domains in tandem in an amino acid chain, e.g., as disclosed in Dai, Lianpan, et al. "A universal design of betacoronavirus vaccines against COVID-19, MERS, and SARS," Cell 182.3 (2020): 722-733, the contents of which are incorporated by reference herein in their entirety.

[00976] In some embodiments, a SARS-CoV-2 S protein, or an immunogenic fragment thereof comprises one or more mutations to alter or remove a glycosylation site, e.g., as described in WO2022221835A2, US20220323574A1, or WO2022195351A1.

[00977] In some embodiments, compositions or medical preparations described herein comprise RNA encoding an amino acid sequence comprising SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof. Likewise, methods described herein comprise administration of such RNA.

[00978] The active platform for use herein is based on an antigen-coding RNA vaccine to induce robust neutralising antibodies and accompanying/concomitant T cell response to achieve protective immunization with preferably minimal vaccine doses. The RNA administered is preferably in-vitro transcribed RNA.

[00979] Three different RNA platforms are particularly preferred, namely non-modified uridine containing mRNA (uRNA), nucleoside modified mRNA (modRNA) and self-amplifying RNA (saRNA). In one particularly preferred embodiment, the RNA is in vitro transcribed RNA. In some embodiments, uRNA is mRNA. In some embodiments, modRNA is mRNA.

[00980] In the following, embodiments of these three different RNA platforms are described, wherein certain terms used when describing elements thereof have the following meanings:

[00981] S1S2 protein/SlS2 RBD: Sequences encoding the respective antigen of SARS-CoV-2.

[00982] nsPl, nsP2, nsP3, and nsP4: Wildtype sequences encoding the Venezuelan equine encephalitis virus (VEEV) RNA-dependent RNA polymerase replicase and a subgenomic promotor plus conserved sequence elements supporting replication and translation.

[00983] virUTR: Viral untranslated region encoding parts of the subgenomic promotor as well as replication and translation supporting sequence elements.

[00984] hAg-Kozak: 5'-UTR sequence of the human alpha-globin mRNA with an optimized 'Kozak sequence' to increase translational efficiency.

[00985] Sec: Sec corresponds to a secretory signal peptide (sec), which guides translocation of the nascent polypeptide chain into the endoplasmatic reticulum. In some embodiments, such a secretory signal peptide includes the intrinsic S1S2 secretory signal peptide. In some embodiments, such a secretory signal peptide is a secretory signal peptide from a non-SlS2 protein. For example, an immunoglobulin secretory signal peptide (aa 1-22), an HSV-1 gD signal peptide (MGGAAARLGAVILFWIVGLHGVRSKY), an HSV-2 gD signal peptide (MGRLTSGVGTAALLWAVGLRWCA); a human SPARC signal peptide, a human insulin isoform 1 signal peptide, a human albumin signal peptide, or any other signal peptide described herein.

[00986] Glycine-serine linker (GS): Sequences coding for short linker peptides predominantly consisting of the amino acids glycine (G) and serine (S), as commonly used for fusion proteins.

[00987] Fibritin: Partial sequence of T4 fibritin (foldon), used as artificial trimerization domain.

[00988] TM: TM sequence corresponds to the transmembrane part of a protein. A transmembrane domain can be N-terminal, C-terminal, or internal to an encoded polypeptide. A coding sequence of a transmembrane element is typically placed in frame (i.e., in the same reading frame), 5', 3', or internal to coding sequences of sequences (e.g., sequences encoding polypeptide(s)) with which it is to be linked. In some embodiments, a transmembrane domain comprises or is a transmembrane domain of Hemagglutinin (HA) of Influenza virus, Env of HIV-1, equine infectious anaemia virus (EIAV), murine leukaemia virus (MLV), mouse mammary tumor virus, G protein of vesicular stomatitis virus (VSV), Rabies virus, or a seven transmembrane domain receptor. In some embodiments, the transmembrane part of a protein is from the S1S2 protein.

[00989] FI element: The 3'-UTR is a combination of two sequence elements derived from the "amino terminal enhancer of split" (AES) mRNA (called F) and the mitochondrial encoded 12S ribosomal RNA (called I). These were identified by an ex vivo selection process for sequences that confer RNA stability and augment total protein expression.

[00990] A30L70: A poly(A)-tail measuring 110 nucleotides in length, consisting of a stretch of 30 adenosine residues, followed by a 10 nucleotide linker sequence and another 70 adenosine residues designed to enhance RNA stability and translational efficiency in dendritic cells.

[00991] In some embodiments, vaccine RNA described herein may comprise, from 5' to 3', one of the following structures:

[00992] Cap-5'-UTR-Vaccine Antigen-Encoding Sequence-3'-UTR-Poly(A), or

[00993] Cap- hAg -Kozak-Vaccine Antigen-Encoding Sequence-FI-A30L70.

[00994] In some embodiments, a vaccine antigen described herein may comprise a full-length S protein or an immunogenic fragment thereof (e.g., RBD). In some embodiments where a vaccine antigen comprises a full- length S protein, its secretory signal peptide and/or transmembrane domain may be replaced by a heterologous secretory signal peptide (e.g., as described herein) and/or a heterologous transmembrane domain (e.g., as described herein).

[00995] In some embodiments, a vaccine antigen described herein may comprise, from N-terminus to C- terminus, one of the following structures:

[00996] Signal Sequence-RBD-Trimerization Domain, or

[00997] Signal Sequence-RBD-Trimerization Domain-Transmembrane Domain.

[00998] RBD and Trimerization Domain may be separated by a linker, in particular a GS linker such as a linker having the amino acid sequence GSPGSGSGS. Trimerization Domain and Transmembrane Domain may be separated by a linker, in particular a GS linker such as a linker having the amino acid sequence GSGSGS.

[00999] Signal Sequence may be a signal sequence as described herein. RBD may be a RBD domain as described herein. Trimerization Domain may be a trimerization domain as described herein. Transmembrane Domain may be a transmembrane domain as described herein.

[001000] In one embodiment, a signal sequence comprises the amino acid sequence of amino acids 1 to 16 or 1 to 19 of SEQ ID NO: 1 or the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to this amino acid sequence,

[OO1OO1] In some embodiments, an RBD comprises the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 1, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to this amino acid sequence,

[001002] In some embodiments, a trimerization domain comprises the amino acid sequence of amino acids 3 to 29 of SEQ ID NO: 10 or the amino acid sequence of SEQ ID NO: 10, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to this amino acid sequence; and

[001003] In one embodiment, a transmembrane domain comprises the amino acid sequence of amino acids 1207 to 1254 of SEQ ID NO: 1, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to this amino acid sequence.

[001004] In one embodiment, Signal sequence comprises the amino acid sequence of amino acids 1 to 16 or 1 to 19 of SEQ ID NO: 1 or the amino acid sequence of amino acids 1 to 22 of SEQ ID NO: 31,

[001005] In some embodiments, an RNA polynucleotide comprising a sequence encoding a vaccine antigen (e.g., a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof) or comprising an open reading frame encoding a vaccine antigen (e.g., a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof) such as the nucleotide sequence of SEQ ID NO: 50 or the nucleotide sequence of SEQ ID NO: 53, a variant or fragment thereof, further comprises a 5' cap, e.g., a 5' cap comprising a Capl structure, a 5' UTR sequence, e.g., a 5' UTR sequence comprising the nucleotide sequence of SEQ ID NO: 12, a 3' UTR sequence, e.g., a 3' UTR sequence comprising the nucleotide sequence of SEQ ID NO:

13, 601, or 302, and polyA sequence, e.g., a polyA sequence comprising the nucleotide sequence of SEQ ID NO:

14. In some embodiments, RNA is formulated in a composition comprising ((4-hydroxybutyl)azanediyl)bis(hexane- 6,l-diyl)bis(2-hexyldecanoate), cholesterol, distearoylphosphatidylcholine, and (2-[(polyethylene glycol)-2000]- N,N-ditetradecylacetamide).

[001006] RNA described herein or RNA encoding the vaccine antigen described herein may be non-modified uridine containing RNA (uRNA), nucleoside modified RNA (modRNA) or self-amplifying RNA (saRNA). In some embodiments, uRNA is mRNA. In some embodiments, modRNA is mRNA. In one embodiment, RNA described herein or RNA encoding the vaccine antigen described herein is nucleoside modified RNA (modRNA).

Variant Specific Vaccines

[001007] In some embodiments, an RNA described herein encodes an S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations that are characteristic of a SARS-CoV-2 variant. In some embodiments, an RNA described herein encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an Alpha variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of a Beta variant. In some embodiments, RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of a Delta variant. In some embodiments, RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an Omicron variant (e.g., an S protein comprising one or more mutations characteristic of a BA.l, BA.2, BA.4/5 Omicron variant). In some embodiments, RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an Omicron XBB variant (e.g., an S protein comprising one or more mutations characteristic of an XBB.1.5, XBB.1.16, XBB.2.3, or XBB.2.3.2 variant). In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an BA.l Omicron variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an BA.2 Omicron variant. In some embodiments, an RNA encodes a SARS- CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an BA.2.12.1 Omicron variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of a BA.3 Omicron variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of a BA.4 or BA.5 Omicron variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an XBB variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.1.5 variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.1.16 variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.2.3 variant. In some embodiments, an RNA encodes a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing comprising one or more mutations characteristic of an XBB.2.3.2 variant. In some embodiments, RNA encoding a SARS-CoV-2 S protein, a variant thereof, or a fragment of either of the foregoing

Non-modified uridine RNA (uRNA)

[001008] In some embodiments, a non-modified uridine RNA is a messenger RNA. In some embodiments, the active principle of non-modified messenger RNA drug substance is a single-stranded mRNA that is translated upon entering a cell. In addition to the sequence encoding the coronavirus vaccine antigen (i.e. open reading frame), each uRNA preferably contains common structural elements optimized for maximal efficacy of the RNA with respect to stability and translational efficiency (including, e.g., 5'-cap, 5'-UTR, 3'-UTR, poly(A)-tail as described herein). The preferred 5' cap structure is beta-S-ARCA(Dl) (m27,2'-OGppSpG). The preferred 5'-UTR and 3'-UTR comprise the nucleotide sequence of SEQ ID NO: 12 and the nucleotide sequence of SEQ ID NO: 13, respectively. The preferred poly(A)-tail comprises the sequence of SEQ ID NO: 14.

Nucleoside modified RNA (modRNA)

[001009] In some embodiments, nucleoside modified RNA is mRNA. In some embodiments, the active principle of nucleoside modified RNA (modRNA) drug substance is a single-stranded RNA (e.g., mRNA) that can be translated upon entering a cell. In addition to a sequence encoding a coronavirus vaccine antigen (i.e., open reading frame), each modRNA contains common structural elements optimized for maximal efficacy of the RNA as the uRNA (5'-cap, 5'-UTR, 3'-UTR, poly(A)-tail). Compared to uRNA, modRNA comprises at least one nucleotide modification (e.g., as described herein). In some embodiments, modRNA contains 1-methyl-pseudouridine instead of uridine. The preferred 5' cap structure is m27,3'-OGppp(ml2'-O)ApG. The preferred 5'-UTR and 3'-UTR comprise the nucleotide sequence of SEQ ID NO: 12 and the nucleotide sequence of SEQ ID NO: 13, respectively. The preferred poly(A)-tail comprises the sequence of SEQ ID NO: 14. An additional purification step is applied for modRNA to reduce dsRNA contaminants generated during the in vitro transcription reaction. Self-amplifying RNA (saRNA)

[001010] The active principle of a self-amplifying RNA (saRNA) drug substance is a single-stranded RNA, which self-amplifies upon entering a cell, and a coronavirus vaccine antigen is translated thereafter. In contrast to uRNA and modRNA that preferably code for a single protein, the coding region of saRNA contains two open reading frames (ORFs). The 5 -ORF encodes an RNA-dependent RNA polymerase such as Venezuelan equine encephalitis virus (VEEV) RNA-dependent RNA polymerase (replicase). The replicase ORF is followed 3' by a subgenomic promoter and a second ORF encoding an antigen. Furthermore, saRNA UTRs contain 5' and 3' conserved sequence elements (CSEs) required for self-amplification. The saRNA contains common structural elements optimized for maximal efficacy of the RNA as the uRNA (including, e.g., 5'-cap, 5'-UTR, 3'-UTR, poly(A)- tail). In some embodiments, the saRNA preferably contains uridine. In some embodiments, the saRNA comprises one or more nucleoside modifications as described herein. The preferred 5' cap structure is beta-S-ARCA(Dl) (m27,2'-OGppSpG).

[OO1O11] Cytoplasmic delivery of saRNA initiates an alphavirus-like life cycle. However, saRNA does not encode for alphaviral structural proteins required for genome packaging or cell entry, therefore generation of replication competent viral particles is very unlikely or not possible. Replication does not involve any intermediate steps that generate DNA. The use/uptake of saRNA therefore poses no risk of genomic integration or other permanent genetic modification within the target cell. Furthermore, the saRNA itself prevents its persistent replication by effectively activating innate immune response via recognition of dsRNA intermediates.

[001012] Different embodiments of this platform are as follows:

[001013] RBS004.1 (SEQ ID NO: 24; SEQ ID NO: 7)

[001014] Structure beta-S-ARCA(Dl)-replicase-SlS2-PP-FI-A30L70

[001015] Encoded antigen Viral spike protein (S protein) of the SARS-CoV-2 (S1S2 full-length protein, sequence variant)

[001016] RBS004.2 (SEQ ID NO: 25; SEQ ID NO: 7)

[001017] Structure beta-S-ARCA(Dl)-replicase-SlS2-PP-FI-A30L70

[001018] Encoded antigen Viral spike protein (S protein) of the SARS-CoV-2 (S1S2 full-length protein, sequence variant)

[001019] BNT162C1; RBS004.3 (SEQ ID NO: 26; SEQ ID NO: 5)

[001020] Structure beta-S-ARCA(Dl)-replicase-RBD-GS-Fibritin-FI-A30L70

[001021] Encoded antigen Viral spike protein (S protein) of the SARS-CoV-2 (partial sequence, Receptor

Binding Domain (RBD) of S1S2 protein)

[001022] RBS004.4 (SEQ ID NO: 27; SEQ ID NO: 28)

[001023] Structure beta-S-ARCA(Dl)-replicase-RBD-GS-Fibritin-TM-FI-A30L70

[001024] Encoded antigen Viral spike protein (S protein) of the SARS-CoV-2 (partial sequence, Receptor

Binding Domain (RBD) of S1S2 protein)

Particles

[001025] In some embodiments, an agent to be delivered to a subject, e.g., a nucleic acid, a polypeptide, a small molecule, and the like, is encapsulated in a particle. In some embodiments, an agent of the present disclosure is formulated in (e.g., encapsulated in) a particle, as further described herein. In some embodiments, a particle is a nucleic acid particle wherein the nucleic acid particle comprises a nucleic acid (e.g., DNA and/or RNA), and a cationic lipid, a cationically ionizable lipid, or a cationic polymer. [001026] A "nucleic acid particle," as used herein, refers to a particle that encompasses or contains a nucleic acid, and, is part of a composition (e.g., a pharmaceutical composition) comprising multiple nucleic acid particles, that is useful for (I) enhancing nucleic acid stability, e.g., during storage, (ii) improving biodistribution of the nucleic acid or delivering a nucleic acid to a target site of interest (e.g., cell, tissue, organ, and the like), and/or (iii) facilitating cell uptake of the nucleic acid. As described herein, a nucleic acid particle may be formed from i) at least one cationic or cationically ionizable lipid or lipid-like material; ii) at least one cationic polymer such as polyethyleneimine, protamine, or a mixture thereof (i.e., a mixture of i) and ii)), and iii) a nucleic acid. Nucleic acid particles described herein include lipid nanoparticles (LNP), lipoplexes (LPX), liposomes, and polyplexes (PLX).

[001027] Electrostatic interactions between positively charged molecules such as cationic polymers and cationic lipids and negatively charged nucleic acids are involved in particle formation. This results in complexation and spontaneous formation of nucleic acid particles. The characteristics of a particle (e.g., nanoparticle) are determined, at least in part, from the components used to form the particle and the process used to prepare the particle. A description of the different types of particles and their structures is provided in ACS Nano 2021, 15, 11, 16982-17015.

[001028] In some embodiments, a nucleic acid particle described herein is a nanoparticle. As used in the present disclosure, "nanoparticle" refers to a particle having an average diameter suitable for parenteral administration and is less than 1000 nm in diameter. In some embodiments, a composition comprising nanoparticles can have an average nanoparticle size (e.g., mean diameter) of about 30 nm to about 150 nm, about 40 nm to about 120 nm, about 50 nm to about 100 nm, or about 60 nm to about 90 nm. In some embodiments, a composition comprising nanoparticles can have an average nanoparticle size (e.g., mean diameter) of about 40 nm to about 120 nm. The term "average diameter" or "mean diameter" refers to the mean hydrodynamic diameter of particles as measured by dynamic laser light scattering (DLS) with data analysis using an appropriate algorithm (e.g., the so-called cumulant algorithm for monodisperse samples), which provides as results the so-called Z-average with the dimension of a length, and the polydispersity index (PDI), which is dimensionless (Koppel, D., J. Chem. Phys. 57, 1972, pp 4814-4820, ISO 13321). Here "average diameter," "mean diameter," "diameter," or "size" for particles is used synonymously with this value of the Z-average.

[001029] A composition comprising nucleic acid particles can be characterized by its polydispersity index, that is, the relative uniformity of particles within a given composition. For example, compositions described herein may exhibit a polydispersity index (PDI) less than about 0.5, less than about 0.4, less than about 0.3, or about 0.2 or less of said nanoparticles. In some embodiments, a composition comprising nucleic acid particles, as described herein, may exhibit a PDI less than about 0.3. By way of example, a composition comprising nucleic acid particles described herein can exhibit a PDI in a range of about 0.1 to about 0.3, or about 0.2 to about 0.3. The polydispersity index of a given composition can be calculated based on dynamic light scattering measurements by the so-called cumulant analysis as mentioned in the definition of the "average diameter." Under certain prerequisites, it can be taken as a measure of the size distribution of an ensemble of ribonucleic acid nanoparticles.

[001030] Nucleic acid particles described herein can be characterized by an "N/P ratio," which is the molar ratio of cationic (nitrogen) groups (the "N" in N/P) in the cationic lipid or polymer to the anionic (phosphate) groups (the "P" in N/P) in RNA. It is understood that a cationic group is one that is either in permanently cationic form (e.g., N+), or one that is ionizable to become cationic (e.g., under certain pH conditions). Use of a single number in an N/P ratio (e.g., an N/P ratio of about 5) is intended to refer to that number over 1, e.g., an N/P ratio of about 4 is intended to mean about 4:1. In some embodiments, a nucleic acid particle (e.g., an RNA LNP) described herein has an N/P ratio greater than or equal to 1, greater than or equal to 2, or greater than or equal to 4. In some embodiments, a nucleic acid particle (e.g., an RNA LNP) described herein has an N/P ratio that is less than 24, less than 18, or less than 12. In some embodiments, a nucleic acid particle (e.g., an RNA LNP) described herein has an N/P ratio that is from about 2 to about 24, about 4 to about 18, about 4 to about 12, or about 4 to about 8. In some embodiments, a nucleic acid particle (e.g., a ribonucleic acid particle) described herein has an N/P ratio that is about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. In some embodiments, an N/P ratio for a nucleic acid particle (e.g., an RNA LNP) described herein is about 6.

[001031] Nucleic acid particles described herein can be prepared using a wide range of methods that may involve obtaining a colloid from at least one cationic or cationically ionizable lipid or lipid-like material and/or at least one cationic polymer and mixing the colloid with nucleic acid to obtain nucleic acid particles. As used herein, an "ionizable" lipid, e.g., a "cationically ionizable" lipid or "ionizable" polymer, e.g., a "cationically ionizable" polymer is a lipid or polymer that may be, in some embodiments, neutral at physiological pH, but is capable of becoming cationic (i.e., becoming positively charged) at acidic pH.

[001032] The present disclosure describes particles comprising nucleic acid, at least one cationic or cationically ionizable lipid or lipid-like material, and/or at least one cationic polymer which associate with the nucleic acid to form nucleic acid particles (e.g., RNA nanoparticles) and compositions comprising such particles. The nucleic acid particles (e.g., RNA nanoparticles) may comprise nucleic acid which is complexed by different non-covalent interactions (e.g., electrostatic, hydrogen bonding, pi-stacking, van der Waals, etc.) to the particle. In some embodiments, the particles described herein are not viral particles, in particular, they are not infectious viral particles, i.e., they are not able to virally infect cells.

[001033] In a nucleic acid particle (e.g., RNA nanoparticle) composition, it is possible that each nucleic acid species is separately formulated as an individual nucleic acid particle formulation. In that case, each individual nucleic acid particle formulation will comprise one nucleic acid species. In some embodiments, a composition comprises more than one individual nucleic acid particle (e.g., RNA nanoparticle) formulation. Respective pharmaceutical compositions are referred to as "mixed particulate formulations." Such mixed particulate formulations may be obtainable by forming, separately, individual nucleic acid particle formulations, and mixing these to produce a formulation comprising a mixed population of nucleic acid-containing particles. Alternatively, different nucleic acid species may be formulated together as a "combined particulate formulation." Such formulations may be obtainable by mixing a combined formulation of different nucleic acid species with a particleforming agent, to produce particles that comprise more than one nucleic acid species.

[001034] Lipid Nanoparticles (LNPs)

[001035] In some embodiments, a particle described herein is a lipid nanoparticle (LNP). LNPs have emerged as particularly useful vehicles for delivery of nucleic acids, for example as described in Theranostics, 2022 Oct 24;12(17):7509-7531. It is understood that a LNP is structurally distinct from other nanoparticles previously used for nucleic acid delivery, such as a liposome, or a lipoplex. LNPs, as described herein, typically do not comprise a bilayer (uni-lamellar), or a concentric series of multiple bilayers (multi-lamellar) separated by aqueous compartments, enclosing a central aqueous compartment. Moreover, LNPs, as described herein, typically do not comprise a central aqueous core or compartment. LNPs as described herein typically comprise nucleic acids (e.g., DNA or RNA such as mRNA) and lipids forming a disordered, non-lamellar phase. LNPs as described herein may be considered as oil-in-water emulsions in which the LNP core materials are preferably in liquid state and hence have a melting point below body temperature. See, e.g., ACS Nano 2021, 15, 11, 16982-17015; Aldosari, et al., Pharmaceutics, 2021, 13, 206.

[001036] LNPs described herein generally comprise four categories of lipids in addition to a nucleic acid agent (e.g., DNA or RNA such as mRNA): a cationic or cationically ionizable lipid (typically a cationically ionizable lipid), a polymer-conjugated lipid, a helper lipid, and a steroid. A person of skill in the art will understand that various combinations of these four categories of lipids can be used to prepare lipid nanoparticles for use in delivering nucleic acid agents.

(i) Cationic or cationically ionizable lipids [001037] As described generally herein, a nucleic acid particle comprises a nucleic acid and a cationic or a cationically ionizable lipid. In some embodiments, a cationic or cationically ionizable lipid useful for incorporation into a nucleic acid particle are those lipids having a polar head group and an aliphatic tail. In some embodiments, a cationic lipid is one where the polar head group has a permanently positive charge (for example, comprising a quaternary ammonium group). In some embodiments, a cationically ionizable lipid is a lipid wherein, at a given pH and in the context of an LNP, the lipid becomes positively charged, such as at below physiological pH (e.g., below pH about 7.4) or neutral pH (e.g., a pH around 7 to 7.5), or in some embodiments, at a pH of less than 7 (e.g., less than 6). In some embodiments, a cationically ionizable lipid is one comprising polar head group that comprises one or more a tertiary amine groups (or secondary or primary amine group) that can become positively charged. LNPs typically comprise cationically ionizable lipids.

[001038] In some embodiments, a lipid nanoparticle comprises about 30 mol% to about 60 mol% of a cationic or cationically ionizable lipid. In some embodiments, a lipid nanoparticle comprises about 35 mol% to about 55 mol% of a cationic or cationically ionizable lipid. In some embodiments, a lipid nanoparticle comprises about 40 mol% to about 50 mol% of a cationic or cationically ionizable lipid. In some embodiments, a lipid nanoparticle comprises about 50 mol% of a cationic or cationically ionizable lipid. In some embodiments, a lipid nanoparticle comprises about 47.0, 47.1, 47.2, 47.3, 47.4, 47.5, 47.6, 47.7, 47.8, 47.9, or 48.0 mol% of a cationic or cationically ionizable lipid. In some embodiments, a lipid nanoparticle comprises 47.5 mol% of a cationic or cationically ionizable lipid.

[001039] Suitable cationic or cationically ionizable lipids are readily identified by those of skill in the art. In some embodiments, a cationic lipid or cationically ionizable lipid is one provided in WO 2010/144740 or WO 2012/016184, which are incorporated herein by reference in their entirety. For example, in some embodiments, a cationic lipid is selected from N-(2,3-dioleyloxypropyl)-N,N,N-trimethylammonium chloride (DOTMA); N,N- distearyl-N,N-dimethylammonium bromide (DDAB), N-(2,3-dioleoyloxypropyl)-N,N,N-trimethylammonium chloride (DOTAP), N,N-dioleyl-N,N-dimethylammonium chloride (DODAC); 3-(N-(N',N'dimethylaminoethane)- carbamoyl)cholesterol (DC-Chol), and N-(l,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethyl ammonium bromide (DMRIE). In some embodiments, a cationically ionizable lipid is selected from l,2-dioleoyl-3- dimethylammonium propane (DODAP); N,N-dimethyl-(2,3-dioleoyloxypropyl)amine (DODMA); and 4- (dimethylamino)-butanoic acid, (10Z,13Z)-l-(9Z,12Z)-9,12-octadecadien-l-yl-10,13-nonadecadien-l-yl ester (DLin-MC3-DMA).

[001040] In some embodiments, a cationically ionizable lipid is a lipid described in WO 2017/075531 or WO 2018/081480, each of which is incorporated by reference herein in its entirety. In some embodiments, a cationically ionizable lipid is a lipid represented by formula CL-I:

[001041] CL-I

[001042] or a pharmaceutically acceptable salt thereof, wherein, as applied to formula CL-I: one of LI or L2 is -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -S(O)x-, -S-S-, -C(=O)S-, -SC(=O)-, -NRaC(=O)-, -C(=O)NRa-, - NRaC(=O)NRa-, -OC(=O)NRa- or -NRaC(=O)O-, and the other of LI or L2 is -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, - S(O)x-, -S-S-, -C(=O)S-, -SC(=O)-, -NRaC(=O)-, -C(=O)NRa-, -NRaC(=O)NRa-, -OC(=O)NRa- or -NRaC(=O)O- or a direct bond; G1 and G2 are each independently unsubstituted C1-C12 alkylene or C1-C12 alkenylene; G3 is Cl- C24 alkylene, C1-C24 alkenylene, C3-C8 cycloalkylene, or C3-C8 cycloalkenylene; Ra is H or C1-C12 alkyl; R1 and_{R2 are each independently C6-C24 alkyl or C6-C24 alkenyl; R3 is H, OR5, CN, - - -} -C12 alkyl; R5 is H or C1-C6 alkyl; and x is 0, 1 or 2. [001043] In some embodiments, a cationically ionizable lipid is ((4-hydroxybutyl)azanediyl)bis(hexane-6,1- diyl) bis(2-hexyldecanoate) (ALC-0315) or ((3-hydroxypropyl)azanediyl)bis(nonane-9,1-diyl) bis(2-butyloctanoate) (ALC-366): ALC-0315 ALC-0366 [001044] In some embodiments, a lipid nanoparticle comprises about 40 mol% to about 50 mol% of a cationically ionizable lipid. In some embodiments, a lipid nanoparticle comprises about 47.0, 47.1, 47.2, 47.3, 47.4, 47.5, 47.6, 47.7, 47.8, 47.9, or 48.0 mol% of a cationically ionizable lipid. In some embodiments, a lipid nanoparticle comprises 47.5 mol% of a cationically ionizable lipid. [001045] In some embodiments, a cationic lipid is one described in WO 2017/049245, which is incorporated by reference in its entirety. In some embodiments, a cationic lipid is represented by formula CL-II [001046] CL-II [001047] or a pharmaceutically acceptable salt thereof, wherein, as applied to formula CL-II: R1 is selected_{from the group consisting of C5-30 alkyl, C5-20 alkenyl, - - and -selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, - - -} together with the atom to which they are attached, form a heterocycle or carbocycle; R4 is selected from the group consisting of a C3-6 carbocycle, -(CH2)nQ, -(CH2)nCHQR, -CHQR, -CQR2, and unsubstituted C1-6 alkyl, where Q is selected from a carbocycle, heterocycle, -OR, -O(CH2)nNR2, -C(O)OR, OC(O)R, -CX3, -CX2H, -CXH2, -_{CN, -NR2, -C(O)NR2, -NRC(O)R, -NRS(O)2R, -NRC(O)NR2, -NRC(S)NR2, -NRR8, -O(CH2)nOR, - -} -OC(O)NR2, -NRC(O)OR, -N(OR)C(O)R, -N(OR)S(O)2R, -N(OR)C(O)OR, -N(OR)C(O)NR2, - - _{- - -C(O)NROR, and -} CRNR2C(O)OR, and each n is independently selected from 1, 2, 3, 4, and 5; each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; -C(O)O-, -OC(O)-, - -_{, - -, -C(O)-, -C(S)-, -C(S)S-, -SC(S)-, -CH(OH)-, - -, -S(O)2-, -S-S-, an aryl group,} and a heteroaryl group; R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H; R8 is selected from the group consisting of C3-6 carbocycle and heterocycle; R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, -OR, -S(O)2R, -S(O)2NR2, C2-6 alkenyl, C3-6 carbocycle and heterocycle; each R is independently selected from the group consisting of C1-3 alkyl, C2-3_{selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, - -} selected from the group consisting of C3-14 alkyl and C3-14 alkenyl; each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl; each Y is independently a C3-6 carbocycle; each X is independently selected from the group consisting of F, Cl, Br, and I; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.

[001048] In some embodiments, a cationically ionizable lipid is heptadecan-9-yl 8-{(2-hydroxyethyl)[6-oxo-6- (undecyloxy)hexyl]amino}octanoate) (SM-102):

[001049] SM-102

[001050] In some embodiments, a cationically ionizable lipid is a lipid described in WO 2015/095340, which is incorporated by reference herein in its entirety. In some embodiments, a cationic lipid is represented by formula CL-III

[001051] CL-III

[001052] or a pharmaceutically acceptable salt thereof, wherein, as related to formula CL-III: n and p are each, independently, 0, 1 or 2; LI is -0C(0)-, -C(0)0- or a bond; R1 is heterocyclyl, heterocyclyl-Cl-8-alkyl or heterocyclyl-Cl-8-alkoxyl, each of which may be optionally substituted with 1, 2, 3, 4 or 5 groups, independently selected from halogen, formidamidine, Cl-8-alkyl, C3-7-cycloalkyl, C3-7-cydoalkyl-Cl-8-alkyl, heterocyclyl, -[(Cl- C4)alkylene]v-N(R')R", -O-[(C1-C4)alkylene]v-N(R')R" or -N(H)-[(C1-C4)alkylene]v-N(R')R", where said (Cl- C4)alkylene is optionally substituted with one or more R groups; v is 0, 1, 2, 3 or 4; R is hydrogen or -Cl-8-alkyl or when v is 0 R is absent; R' and R", are each, independently, hydrogen, -Cl-8-alkyl; or R' and R" combine with the nitrogen to which they are bound, and optionally including another heteroatom selected from N, O and S, to form a 5-8 membered heterocycle or heteroaryl, optionally substituted with an -Cl-8-alkyl, hydroxy or cycloalkyl- C1-8-;

[001053] R2 and R3 are each, independently, C7-22 alkyl, C12-22 alkenyl, C3-8 cycloalkyl optionally substituted with 1, 2, or 3 Cl-8 alkyl groups,

[001054] R4 is selected from hydrogen, Cl-14 alkyl,

[001056] In some embodiments, a cationically ionizable lipid is represented by

[001057] In some embodiments, a cationic lipid is one described in WO 2018/087753, which is incorporated herein by reference in its entirety.

[001] In some embodiments, a cationic lipid is represented by formula CL-IV:

[001058] or a pharmaceutically acceptable salt thereof, wherein, as applied for formula CL-IV: Y is O or NH; T is C or S; W is a bond, O, NH or S; R1 is selected from the group consisting of: (a) NR4R5, wherein R4 and R5 are each independently a C1-C4 alkyl; or R4 and R5 together with the nitrogen to which they are attached form a 5 or 6 membered heterocyclic or heteroaromatic ring, optionally containing one or more additional heteroatoms selected from the group consisting of O, N and S; or NR4R5 represent a guanidine group (-NHC(=NH)NH2); (b) the side chain of a natural or unnatural amino acid; and (c) a 5 or 6 membered heterocyclic or heteroaromatic ring containing one or more heteroatoms selected from the group consisting of O, N and S; R2 and R3 are selected from the group consisting of: (a) C10-C22 alkyl; (b) C10-C22 alkenyl; (c) C10-C22 alkynyl; (d) C4- C10 alkylene-Z-C4-C22 alkyl; and (e) C4-C10 alkylene-Z-C4-C22 alkenyl; Z is -0-C(=0)-, -C(=0)-0- or -0-; n is 0, 1, 2, 3, 4, 5 or 6; m is 0 or 1; p is 0 or 1; and z is 0 or 2.

[001] In some embodiments, a cationically ionizable lipid is selected from:

^001059] In some embodiments, a cationically ionizable lipid is one described in WO 2022/081750, which is incorporated herein by reference in its entirety.

In some embodiments, a cationically ionizable lipid is represented by formula CL-V-1 :

[001060] or a pharmaceutically acceptable salt thereof, wherein, as applied to formula CL-V-l:

[001061] each R1 and each R2 is independently selected from the group consisting of H, an optionally substituted C1-C22 alkyl, optionally substituted C2-C22 alkenyl, optionally substituted C2-C22 alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C4-C6 heterocycloalkyl, optionally substituted C4-

C6 alkylcycloalkyl, optionally substituted C4-C6 aryl, optionally substituted C3-C6 heteroaryl, optionally substituted C4-C8 aryloxy, optionally substituted C7-C10 arylalkyl, optionally substituted C5-C10 heteroaryl alkyl group, optionally substituted amine; or Rl and R2 can together form a 3-7 membered heterocycloalkyl or heteroaryl ring; each R3, R4, R13 and R14 is independently selected from the group consisting of an optionally substituted C1-C22 alkyl, optionally substituted C2-C22 alkenyl, optionally substituted C2-C22 alkynyl; each R5, R6, R7, R8, R9, RIO, R15, and R16 is independently selected from the group consisting of H, OH, halo, phenyl, benzyl, optionally substituted C1-C22 alkyl, optionally substituted C2-C22 alkenyl, optionally substituted C2-C22 alkynyl; each of w, x, y, and z is independently an integer from 0-10; each Q is independently an atom selected from O, NH, NR1, and S; each of m is an integer from 0 to 8, preferably 0, 1, or 2; and each of LI and L2 is independently selected from the group consisting of -C(=O)-; -OC(=O)-; -OC(=O)O-; -C(=O)O-; - C(=O)O(CR5R6R7)-; -NH-C(=O)-; -C(=O)NH-; -SO-; - SO2-; -SO3-; -NS02-; -S02N-; -NH((C1-C8)alkyl)-; -N((C1-

C8)alkyl)2-; -NH((C6)aryl)-; -N((C6)aryl)2-; -NHC(=O)NH-; -NHC(=O)O-; -OC(=O)NH-; -NHC(=O)NR1-; -

NHC(=O)O-; -OC(=O)NR1-; -C(=O)R1-; -CO((Cl-C8)alkyl)-; -CO((C6)aryl)-; -CO2((Cl-C8)alkyl)-; - CO2((C6)aryl)- ; -SO2((Cl-C8)alkyl)-; and -SO2((C6)aryl)-.

[001062] In some embodiments, a cationically ionizable lipid is represented by formula CL-V-2:

[001064] or a pharmaceutically acceptable salt thereof, wherein, as applied to CL-V-2:

[001065] each Rl', Rl, R2, Rll, and R12 is independently selected from the group consisting of H, an optionally substituted C1-C22 alkyl, optionally substituted C2-C22 alkenyl, optionally substituted C2-C22 alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C4-C6 heterocycloalkyl, optionally substituted C4- C6 alkylcycloalkyl, optionally substituted C4-C6 aryl, optionally substituted C3-C6 heteroaryl, optionally substituted C4-C8 aryloxy, optionally substituted C7-C10 arylalkyl, optionally substituted C5-C10 heteroarylalkyl group, optionally substituted amine; or Rl and R2 can together form cycloalkyl or heterocycloalkyl ring; if Q is S or 0 the R1 attached to the S or O is an electron pair; each R3 and R4 is independently selected from the group consisting of an optionally substituted C1-C22 alkyl, optionally substituted C2-C22 alkenyl, optionally substituted C2-C22 alkynyl; each R5, R6, R7, R8, R9, and RIO is independently selected from the group consisting of H, OH, halo, phenyl, benzyl, optionally substituted C1-C22 alkyl, optionally substituted C2-C22 alkenyl, optionally substituted C2-C22 alkynyl; each of x, y, and z is independently an integer from 0-10; G and Q are each independently an atom selected from CH, O, N, and S; each of m and n is an integer from 0-8; and each of LI and L2 is independently selected from the group consisting of -C(=O)-; -OC(=O)-; -OC(=O)O-; -C(=O)O-; - C(=O)O(CR1R2R3)-; -NH-C(=O)-; -C(=O)NH-; -SO-; -SO2-; -SO3-; -NS02-; -S02N-; -NH((C1-C8)alkyl)-; -N((C1- C8)alkyl)2-; -NH((C6)aryl)-; -N((C6)aryl)2-; -NHC(=O)NH-; -NHC(=O)O-; -OC(=O)NH-; -NHC(=O)NR1-; - NHC(=O)O-; -OC(=O)NR1-; -C(=O)R1-; -CO((Cl-C8)alkyl)-; -CO((C6)aryl)-; -CO2((Cl-C8)alkyl)-; -CO2((C6)aryl)- ; -SO2((Cl-C8)alkyl)-; and -SO2((C6)aryl)-.

[002] In some embodiments, a cationically ionizable lipid is selected from: di(heptadecan-9-yl) 3,3'-((2-(4- methylpiperazin-l-yl)ethyl)azanediyl)dipropionate (BHD-C2C2-PipZ); bis(2-octyldodecyl) 3,3'-((2-(l- methylpyrrolidin-2-yl)ethyl)azanediyl)dipropionate (BODD-C2C2-lMe-Pyr); bis(2-octyldodecyl) 3,3'-((2-(pyrrolidin- l-yl)ethyl)azanediyl)dipropionate (BODD-C2C2-Pyr); bis(2-octyldodecyl) 3,3'-(((l-methylpiperidin-3- yl)methyl)azanediyl)dipropionate (BODD-C2C2-lMe-3PipD); bis(2-octyldodecyl) 3,3'-((2-

(dimethylamino)ethyl)azanediyl)dipropionate (BODD-C2C2-DMA); bis(2-octyldodecyl) 3,3'-((4-(4-methylpiperazin- l-yl)butyl)azanediyl)dipropionate (BODD-C2C4-PipZ); bis(2-octyldodecyl) 3,3'-((4-(pyrrolidin-l- yl)butyl)azanediyl)dipropionate (BODD-C2C4-Pyr); and bis(2-hexyldecyl) 3,3'-((4-(4-methylpiperazin-l- yl)butyl)azanediyl)dipropionate (BHD-C2C4-PipZ).

[001066] In some embodiments, a lipid nanoparticle (LNP) comprises a cationic or cationically ionizable lipid selected from the group consisting of: BHD-C2C2-PipZ, BODD-C2C2-lMe-Pyr, ALC-0315, ALC-366, SM-102, HY- 501, EA-405, HY-405, DODMA, and Dlin-MC3-DMA. In some embodiments, a LNP comprises a cationic or cationically ionizable lipid selected from the group consisting of: BHD-C2C2-PipZ, BODD-C2C2-lMe-Pyr, ALC-0315, SM-102, HY-501, and DODMA. In some embodiments, a LNP comprises about 40 mol% to about 50 mol% (e.g., about 47.5 mol%) (relative to the total amount of lipids in a LNP) of a cationic or cationically ionizable lipid selected from the group consisting of: BHD-C2C2-PipZ; BODD-C2C2-lMe-Pyr; ALC-0315; ALC-0366; SM-102; HY- 501; EA-405; HY-405; DODMA; and Dlin-MC3-DMA. In some embodiments, a LNP comprises about 40 mol% to about 50 mol% (e.g., about 47.5 mol%) (relative to the total amount of lipids in a LNP) of a cationic or cationically ionizable lipid selected from the group consisting of: BHD-C2C2-PipZ; BODD-C2C2-lMe-Pyr; ALC-315, SM-102; HY-501; and DODMA.

(ii) Helper lipids

[001067] As described herein, lipid nanoparticles of the present disclosure comprise a helper lipid. In some embodiments, a helper lipid is or comprises phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phosphatidic acids, phosphatidylserines or sphingomyelin. In some embodiments, a helper lipid is a phospholipid. In some embodiments, a helper lipid is or comprises l,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), l,2-dimyristoyl-sn-glycero-3- phosphocholine (DM PC), l-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), l,2-dioleoyl-sn-glycero-3- phosphocholine (DOPC), phosphatidylethanolamines such as l,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), distearoyl-phosphatidylethanolamine (DSPE), sphingomyelins, N-palmitoyl-D-erythro- sphingosylphosphorylcholine (SM), l,2-diacylglyceryl-3-O-4'-(N,N,N-trimethyl)-homoserine (DGTS), ceramides, and their derivatives. In some embodiments, a helper lipid is selected from the group consisting of DSPC, DOPC, DMPC, DPPC, POPC, DOPE, DSPE, and SM. In some embodiments, the helper lipid is selected from the group consisting of DSPC, DPPC, DMPC, DOPC, POPC, DOPE and SM. In some embodiments, the helper lipid is DSPC. [001068] Helper lipids may be synthetic or naturally derived. Other helper lipids suitable for use in a lipid nanoparticle are described in WO 2021/026358, WO 2017/075531, and WO 2018/081480, the entire contents of each of which are incorporated herein by reference.

[001069] In some embodiments, a lipid nanoparticle comprises about 5 to about 15 mol% of a helper lipid. In some embodiments, a lipid nanoparticle comprises about 5 to about 15 mol% of a phospholipid. In some embodiments, a lipid nanoparticle comprises about 8 to about 12 mol% of a phospholipid. In some embodiments, a lipid nanoparticle comprises about 10 mol% of a phospholipid. In some embodiments, a lipid nanoparticle comprises about 5 to about 15 mol% of DSPC. In some embodiments, a lipid nanoparticle comprises about 8 to about 12 mol% of DSPC. In some embodiments, a lipid nanoparticle comprises about 10 mol% of DSPC. a. Polymer-conjugated lipids

[001070] As described herein, LNPs of the present disclosure comprise a polymer-conjugated lipid. In some embodiments, a polymer-conjugated lipid is a lipid conjugated to polyethylene glycol (a "PEG-lipid"). In some embodiments, a PEG-lipid is selected from pegylated diacylglycerol (PEG-DAG) such as l-(monomethoxy- polyethylene glycol)-2,3-dimyristoylglycerol (PEG-DMG) (e.g., l,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DMG)), a pegylated phosphatidylethanolamine (PEG-PE), a PEG succinate diacylglycerol (PEG-S-DAG) such as 4-0-(2',3'-di(tetradecanoyloxy)propyl-l-0-(cjo-methoxy(polyethoxy)ethyl)butanedioate (PEG- S-DMG), l,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000 amine), a pegylated ceramide (PEG-cer), or a PEG dialkoxypropylcarbamate such as co-methoxy(polyethoxy)ethyl- N-(2,3-di(tetradecanoxy)propyl)carbamate, and 2,3-di(tetradecanoxy)propyl-N-(co- methoxy(polyethoxy)ethyl)carbamate. In some embodiments, a PEG group that is part of a PEG-lipid has, on average in a composition comprising one or more PEG-lipid molecules, a number average molecular weight (Mn) of about 2000 g/mol.

[001071] In some embodiments, a PEG-lipid is DMG-PEG. In some embodiments, a PEG-lipid is PEG2000- DMG:

[001073] In some embodiments, a PEG-lipid is provided in WO 2021/026358, WO 2017/075531, or WO 2018/081480, each of which is incorporated by reference in its entirety.

[001074] In some embodiments, a PEG-lipid is a compound of Formula PCL-I:

[001076] or a pharmaceutically acceptable salt thereof, wherein, as applied to formula PGL-I, R8 and R9 are each independently C10-C30 aliphatic, optionally interrupted by one or more ester bonds, and w is an integer from 30 to 60. In some embodiments, a compound of Formula PCL-I is 2-[(polyethylene glycol)-2000]-N,N- ditetradecylacetamide (ALC-0159). In some embodiments, a compound of Formula PCL-I is:

[001077]

[001078] or a pharmaceutically acceptable salt thereof, where n' is an integer from about 45 to about 50.

[001079] In some embodiments, the PEG-lipid is represented by:

[001080]

[001081] wherein n has a mean value ranging from 30 to 60. In some embodiments, n is 50. In one embodiment, the PEG-conjugated lipid (pegylated lipid) is PEG2000-C-DMA which preferably refers to 3-N-[(w- methoxy polyethylene glycol)2000)carbamoyl]-l,2-dimyristyloxy-propylamine (MPEG-(2 kDa)-C-DMA) or methoxy-polyethylene glycol-2,3-bis(tetradecyloxy) propylcarbamate (2000).

[001082] In some embodiments, a PEG-lipid is selected from PEG-DAG, PEG-PE, PEG-S-DAG, PEG2000-DMG, ALC-159, PEG2000-C-DMA PEG-S-DMG, PEG-cer, and combinations thereof. In some embodiments, a PEG-lipid is

ALC-0159 or PEG2000-DMG. In some embodiments, a PEG-lipid is ALC-0159. In some embodiments, a PEG-lipid is PEG2000-DMG.

[001083] In some embodiments, a polymer-conjugated lipid is a polysarcosine-conjugated lipid, also referred to herein as sarcosinylated lipid or pSar-lipid. The term "sarcosinylated lipid" refers to a molecule comprising both a lipid portion and a polysarcosine (poly(N-methylglycine)) portion. [001084] In some embodiments, a polymer-conjugated lipid is one described in WO 2024/028325, which is incorporated herein by reference in its entirety. In some embodiments, a polymer-conjugated lipid is represented by formula PCL-II: -II of, wherein, as applied to formula PCL-II: X2 and X1

y substituted thioamide, ester, or thioester; Y is -CH2-, - (CH2)2-, or –(CH2)3-; z is 2 to 24; and n is 1 to 100. In some embodiments of formula PCL-II: (i) when X1 is - C(O)- then X2 is -NR1-; (ii) when X1 is -NR1- then X2 is -C(O)-; (iii) when X1 is -C(S)- then X2 is -NR1-; (iv) when X1 is -NR1- then X2 is -C(S)-; (v) when X1 is -C(O)- then X2 is -O-; (vi) when X1 is -O- then X2 is -C(O)-; (vii) when X1 is -C(S)- then X2 is -O-; (viii) when X1 is -O- then X2 is -C(S)-; (ix) when X1 is -C(O)- then X2 is -S-; or (x) when X1 is -S- then X2 is -C(O)-; wherein R1 is hydrogen or C1-8 alkyl. In some embodiments of formula PCL-II: (i) when X1 is -C(O)- then X2 is -NR1-; (ii) when X1 is -NR1- then X2 is -C(O)-; (iii) when X1 is -C(S)- then X2 is -NR1-; (iv) when X1 is -NR1- then X2 is -C(S)-; (v) when X1 is -C(O)- then X2 is -O-; or (vi) when X1 is -O- then X2 is -C(O)-; wherein R1 is hydrogen or C1-8 alkyl. [001] In some embodiments, a polymer-conjugated lipid comprises monomers of 2-(2-(2- aminoethoxy)ethoxy)acetic acid. In some embodiments, the polymer of the polymer-conjugated lipid is or comprises poly-2-(2-(2-aminoethoxy)ethoxy)acetic acid (pAEEA) or poly-2-(2-(2-methylaminoethoxy)ethoxy)acetic acid (pMAEEA), or a derivative thereof. In some embodiments, a polymer-conjugated lipid comprises monomers of unit PCL-II-1: -1 [002] ed lipid comprises, 5 to 50, 5 to 25 or 10 to 25 monomers of

PCL-II-1. In some embodiments, a polymer-conjugated lipid comprises 14 to 17 monomers of PCL-II-1. In some embodiments, a polymer-conjugated lipid comprises 8 to 14 monomers of PCL-II-1. In some embodiments, a polymer-conjugated lipid is selected from the table below: DSPE- AEEA14 A

[001087] In some embodiments, an LNP comprises an polysarcosine-conjugated or a pAEEA/pMAEEA- conjugated lipid, as described herein. In some embodiments, nucleic acid particles (e.g., DNA or RNA particles) described herein comprise a polysarcosine-conjugated or a pAEEA/pMAEEA-conjugated lipid and are substantially free of a pegylated lipid (or do not contain a pegylated lipid).

[001088] In some embodiments, a lipid nanoparticle comprises about 0.5 to about 5.0 mol% of a polymer- conjugated lipid. In some embodiments, a lipid nanoparticle comprises about 1.0 to about 2.5 mol% of a polymer-conjugated lipid. In some embodiments, a lipid nanoparticle comprises about 1.5 to about 2.0 mol% of a polymer-conjugated lipid. In some embodiments, a lipid nanoparticle comprises about 1.5 to about 1.8 mol% of a polymer-conjugated lipid. In some embodiments, a lipid nanoparticle comprises about 1.5 mol% to about 1.8 mol% (relative to the total amount of lipids in a lipid nanoparticle) of a polymer-conjugated lipid selected from the group consisting of: DSPE-AEEA14-AC; VE-AEEA14-AC; ALC-0159 and PEG2000-DMG. In some embodiments, a lipid nanoparticle comprises about 1.5 mol% to about 1.8 mol% (relative to the total amount of lipids in a lipid nanoparticle) of a polymer-conjugated lipid selected from the group consisting of: DSPE-AEEA14-AC, VE-AEEA14- AC, and PEG2000-DMG. In some embodiments, a molar ratio of a cationic or cationically ionizable lipid to a polymer-conjugated lipid is from about 2:1 to about 8:1. b. Steroids

[001089] As described generally herein, lipid nanoparticles further comprise a steroid. In some embodiments, a steroid is a sterol. In some embodiments, a sterol is p-sitosterol, stigmasterol, cholesterol, cholecalciferol, ergocalciferol, calcipotriol, botulin, lupeol, ursolic acid, oleanolic acid, cycloartenol, lanosterol, or o-tocopherol. In some embodiments, a sterol is cholesterol. In some embodiments, a lipid nanoparticle comprises about 39 to about 49 mol% of a steroid. In some embodiments, a lipid nanoparticle comprises about 40 to about 46 mol% of a steroid. In some embodiments, a lipid nanoparticle comprises about 40 to about 44 mol% of a steroid.

[001090] In some embodiments, a lipid nanoparticle comprises: about 30 to about 60 mol% of a cationically ionizable lipid; about 18.5 to about 48.5 mol% of a steroid (e.g., cholesterol); about 0 to about 30 mol% of a helper lipid (e.g., DSPC); and about 0 to about 10 mol% of a polymer-conjugated lipid. In some embodiments, a lipid nanoparticle comprises: about 35 to about 55 mol% of a cationically ionizable lipid; about 30 to about 40 mol% of a steroid (e.g., cholesterol); about 5 to about 25 mol% of a helper lipid (e.g., DSPC); and about 0 to about 10 mol% of a polymer-conjugated lipid. In some embodiments, a lipid nanoparticle comprises: about 40 to about 50 mol% of a cationically ionizable lipid; about 30 to about 45 mol% of a steroid (e.g., cholesterol); about 5 to about 15 mol% of a helper lipid (e.g., DSPC); and about 1 to about 2.5 mol% of a polymer-conjugated lipid. [001091] In some embodiments, a lipid nanoparticle comprises: 47.5 mol% di(heptadecan-9-yl) 3,3'-((2-(4- methylpiperazin-l-yl)ethyl)azanediyl)dipropionate (BHD-C2C2-PipZ); 10 mol% DSPC; 40.7 mol% cholesterol; and 1.8 mol% VE-AEEA14-AC. In some embodiments, a lipid nanoparticle comprises: 47.5 mol% di(heptadecan-9-yl) 3,3'-((2-(4-methylpiperazin-l-yl)ethyl)azanediyl)dipropionate (BHD-C2C2-PipZ); 10 mol% DSPC; 40.7 mol% cholesterol; and 1.8 mol% PEG2000-DMG. In some embodiments, a lipid nanoparticle comprises: about 47.5 mol% of ALC-0315; about 10 mol% of DSPC; about 40.7 mol% of cholesterol; and about 1.8 mol% of ALC-159. In some embodiments, a lipid nanoparticle comprises: about 47.5 mol% of ALC-366; about 10 mol% of DSPC; about 40.7 mol% of cholesterol; and about 1.8 mol% of ALC-159. In some embodiments, a lipid nanoparticle comprises about 50 mol% of SM-102; about 1.5 mol% of PEG2000-DMG; about 10 mol% of DSPC; and about 38.5 mol% of cholesterol. In some embodiments, a lipid nanoparticle comprises: 47.5 mol% bis(2-octyldodecyl) 3,3'-((2-(l-methylpyrrolidin-2-yl)ethyl)azanediyl)dipropionate (BODD-C2C2-lMe-Pyr); 10 mol% DSPC; 40.7 mol% cholesterol; and 1.8 mol% VE-AEEA14-AC. In some embodiments, a lipid nanoparticle comprises: 47.5 mol% bis(2-octyldodecyl) 3,3'-((2-(l-methylpyrrolidin-2-yl)ethyl)azanediyl)dipropionate (BODD-C2C2-lMe-Pyr); 10 mol% DSPC; 40.7 mol% cholesterol; and 1.8 mol% PEG2000-DMG. f v) Manufacturing

[001092] Lipids and lipid nanoparticles comprising nucleic acids and their method of preparation are known in the art, including, e.g., as described in U.S. Patent Publication Nos. 2016/0009637, 2015/0273068, 2014/0200257, 2013/0338210, 2013/0245107, 2013/0123338, 2013/0017223, 2012/0183581, 2012/0027803, 2011/0311583, 2011/0216622, 2011/0117125, 2007/0042031, 2006/0083780, 2005/017054, 2004/0142025, 2007/0042031, 1999/009076 and PCT Pub. Nos. WO 99/39741, WO 2018/081480, WO 2017/004143, WO 2017/075531, WO 2015/199952, WO 2013/086322, WO 2013/016058, WO 2013/086373, WO 2011/141705, WO 2022/016089, WO 2022/081752, the full disclosures of which are herein incorporated by reference in their entirety for the purposes described herein.

[001093] For example, in some embodiments, cationically ionizable lipids, helper lipids, and steroids are solubilized in an organic solvent such as ethanol, at a predetermined weight or molar ratios/percentages (e.g., ones described herein). In some embodiments, lipid nanoparticles are prepared at a total lipid to nucleic acid (e.g., RNA) weight ratio of approximately 10:1 to 50:1. In some embodiments, such nucleic acid (e.g., RNA) can be diluted to 0.1 to 1.0 mg/mL (e.g., 0.4 mg/mL) in an acidic buffer, such as citrate or acetate having a pH of between about 4 to about 6.

[001094] In some embodiments, using an ethanol injection technique, a colloidal lipid dispersion comprising nucleic acids (e.g., RNAs) can be formed as follows: an ethanol solution comprising lipids, such as cationic lipids, helper lipids, steroids, and polymer-conjugated lipids, is combined with, e.g., injected into or continuously mixed with, an aqueous solution comprising nucleic acids.

[001095] In some embodiments, lipid and nucleic acid (e.g., RNA) solutions can be mixed at room temperature by pumping each solution (e.g., a lipid solution comprising a cationic lipid, a helper lipid, cholesterol, a conjugated lipid, and any other additives) at controlled flow rates into a mixing unit, for example, using piston pumps. In some embodiments, the flow rates of a lipid solution and a nucleic acid (e.g., RNA) solution into a mixing unit are maintained at a ratio of 1:3. Upon mixing, nucleic acid-lipid particles are formed as the ethanolic lipid solution is diluted with aqueous nucleic acids (e.g., RNAs). The lipid solubility is decreased, while cationic lipids bearing a positive charge interact with the negatively charged nucleic acid (e.g., RNA).

[001096] In some embodiments, a solution comprising nucleic acid (e.g., RNA)-encapsulated lipid nanoparticles can be processed by one or more of concentration adjustment, buffer exchange, formulation, and/or filtration. Liposomes

[001097] In some embodiments, a nucleic acid particle is a liposome, wherein the liposome comprises a cationic lipid and a nucleic acid. Liposomes are lipid-based particles that comprise a bilayer (uni-lamellar) or a concentric series of multiple bilayers (multi-lamellar) separated by aqueous compartments, enclosing a central aqueous core that encapsulates the agent for delivery (e.g., a nucleic acid such as RNA). Different types of liposomes are described, including e.g., small and large unilamellar vesicles, multilamellar vesicles, multivesicular liposomes. Many suitable methods are known for manufacturing liposomes (see e.g., Shah S, et al., Adv Drug Deliv Rev. 2020;154-155:102-122), including e.g., solvent evaporation or lipid film hydration, solvent dispersion or reverse phase evaporation, optionally followed by processes to manipulate the size of the liposomes, such as e.g., sonication, homogenization and extrusion. Examples of liposomes that may be suitable for nucleic acid (e.g., RNA) delivery are described in PCT App. Pub. No. WO 2012/005378, WO 2013/005825, WO 2019/077053 and WO 2022/069632, each of which is incorporated herein by reference in its entirety.

[001098] In some embodiments, liposomes may be formed from one or more lipids selected from neutral lipids, phospholipids, cholesterol, and/or cationic lipids. In some embodiments, liposomes may comprise one or more phospholipids and optionally cholesterol. Suitable phospholipids for forming liposomes include DSPC, DPPC, DMPC, DOPC, DOPE, and DSPE. In some embodiments, a cationic lipid for use in a liposome is selected from 1,2- dioleoyl-3-dimethylammonium propane (DODAP), N,N-dimethyl-(2,3-dioleoyloxypropyl)amine (DODMA), N-(2,3- dioleyloxypropyl)-N,N,N-trimethylammonium chloride (DOTMA); N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(2,3-dioleoyloxypropyl)-N,N,N-trimethylammonium chloride (DOTAP), 4-(dimethylamino)butanoic acid, and (10Z,13Z)-l-(9Z,12Z)-9,12-octadecadien-l-yl-10,13-nonadecadien-l-yl ester (Dlin-MC3-DMA). In some embodiments a cationic lipid for use in a liposome is selected from DOTMA and DOTAP. In some embodiments a cationic lipid is DOTMA.

[001099] In some embodiments, a liposome may further comprise an additional lipid. In some embodiments, an additional lipid is a neutral lipid. As used herein, a "neutral lipid" refers to a lipid having a net charge of zero. Examples of suitable neutral lipids include, but are not limited to, l,2-di-(9Z-octadecenoyl)-glycero-3- phosphoethanolamine (DOPE), l,2-dioleoyl-glycero-3-phosphocholine (DOPC), diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide, sphingomyelin, cephalin, cholesterol, and cerebroside. In specific embodiments, the second lipid is DOPE, cholesterol and/or DOPC.

Lipoplexes (LPX)

[001100] In some embodiments, a nucleic acid particle is a lipoplex, wherein the lipoplex comprises a cationic lipid and a nucleic acid. Lipoplex particles (LPX) may be prepared by mixing liposomes with nucleic acid (e.g., RNA, where lipoplex particles comprising RNA are referred to as "RNA lipoplex particles"). RNA LPX particles typically form spontaneously from electrostatic interactions between positively charged liposomes and negatively charged RNA, and typically have a multilamellar structure. LPX (e.g., RNA LPX) typically comprise one or more cationic lipids and optionally one or more additional lipids. Examples of lipoplexes that are suitable for nucleic acid (e.g., RNA) delivery, as well as methods of manufacture, are described in PCT App. Pub. No. WO 2019/077053 and WO 2022/069632, each of which is incorporated herein by reference in its entirety.

[001101] In some embodiments, a cationic lipid for use in a LPX is selected from DODAP, DODMA, DOTMA, DDAB, DOTAP, and Dlin-MC3-DMA. In some embodiments a cationic lipid for use in a LPX is selected from DOTMA and DOTAP. In some embodiments a cationic lipid for use in a LPX is DOTMA. In some embodiments, a LPX further comprises an additional lipid. In some embodiments, an additional lipid is a neutral lipid. As used herein, a "neutral lipid" refers to a lipid having a net charge of zero. Examples of suitable neutral lipids include, but are not limited to, DOPE, DOPC, diacylphosphatidyl choline, diacylphosphatidyl ethanol amine, ceramide, sphingomyelin, cephalin, cholesterol, and cerebroside. In specific embodiments, the second lipid is DOPE, cholesterol and/or DOPC.

[001102] In some embodiments, LPX may be manufactured by first preparing liposomes by injecting a solution of the lipids (e.g., DOTMA and DOPE) in ethanol into water or a suitable aqueous phase to form a liposome colloid. LPX may then be prepared by mixing the liposome colloid with a solution comprising nucleic acid (e.g., RNA). In one embodiment, RNA LPX particles comprise DOTMA and DOPE in a molar ratio of from about 10:0 to 1:9, from about 4:1 to 1:2, from about 3:1 to about 1:1, or about 2:1. In one embodiment, the ratio of positive charges (e.g., in DOTMA) to negative charges (e.g., in the RNA), in the RNA LPX particles, is from about 1:2 to 1.9:2, or about 1.3:2.0. RNA LPX particles may have an average diameter that ranges from about 200 to about 800 nm, such as from about 300 nm to about 500 nm.

Polymer-based partides (Polyplexes) and other delivery systems

[001103] In some embodiments, a nucleic acid particle described herein is a polymer-based particle (i.e., a polyplex, PLX). In some embodiments, a nucleic acid particle is a polyplex particle, and comprises a cationic polymer and a nucleic acid. Examples of polyplex particles that are suitable for nucleic acid (e.g., RNA) delivery are described in PCT App. Pub. No. WO 2021/001417, which is incorporated herein by reference in its entirety. Nucleic acid polyplex particles typically form spontaneously from electrostatic interactions between positively charged cationic polymer (e.g., PEI) and negatively charged nucleic acid (e.g., RNA). In some embodiments a polyplex particle may further comprise one or more lipids, in which case it may be referred to as a lipopolyplex (LPLX). In some embodiments, a cationic polymer is a polycationic polymer, e.g., a polymer having one or more cationic or cationically ionizable groups. In some embodiments, one or more cationic or ionizable groups comprise a nitrogen atom. Cationic polymers useful for preparing complexes described herein can be homopolymers, heteropolymers, or block-co-polymers.

[001104] In some embodiments, a cationic polymer is poly(ethylenimine), poly(propylenimine), polybrene, polyallylamine, polyvinylamine, polyamidoamine, poly-L-lysine, poly-L-arginine, poly-L-histidine, poly(2-aminoethyl methacrylate), or a pharmaceutically acceptable salt thereof. In some embodiments, a cationic polymer is a homopolymer. It is understood that a cationic polymer described herein can be linear or branched. In some embodiments, a cationic polymer is linear. In some embodiments, a cationic polymer is poly(ethylenimine).

[001105] In some embodiments, a cationic polymer is a heteropolymer (e.g., a linear heteropolymer) comprising copolymers of one or more of poly(ethylenimine), poly(propylenimine), polybrene, polyallylamine, polyvinylamine, polyamidoamine, poly-L-lysine, poly-L-arginine, poly-L-histidine, and poly(2-aminoethyl methacrylate), or a pharmaceutically acceptable salt thereof. In some embodiments, a cationic polymer is a heteropolymer comprising poly(ethylenimine) and poly(propylenimine).

[001106] In some embodiments, a cationic polymer has between 250 and 2000 repeating monomer units (such as between 1500 and 2000 repeating monomer units). In some embodiments, a cationic polymer is a polymer described herein, having a number average molecular weight (Mn) of about 600 Daltons (Da) to about 400,000 Da (such as about 20,000 to about 120,000 Da).

[001107] In some embodiments, a complex comprises a cationic polymer and a nucleic acid, wherein the cationic polymer is or comprises a polyamine derivative (e.g., a carboxylated polyamine derivative). Suitable polyamine derivatives for delivery of nucleic acids, such as RNA, are described in WO 2014/053245 and WO 2014/056590, both of which are incorporated herein by reference in their entirety. [001108] In some embodiments, a polyamine derivative comprises: a polyamine moiety comprising a plurality of amino groups; a plurality of carboxylated substituents comprising a carboxyl group bonded via a hydrophobic linker to amino groups of said polyamine moiety, wherein each of said carboxylated substituents comprises from 6 to 40 carbon atoms, preferably from 6 to 20 carbon atoms, and more preferably from 8 to 16 carbon atoms, and each of said hydrophobic linker may comprise from 1 to 3 heteroatoms selected from O, N, and S; and a plurality of hydrophobic substituents bonded to amino groups of said polyamine moiety, wherein each of said hydrophobic substituents comprises at least 2 carbon atoms, preferably from 6 to 40 carbon atoms, and may comprise from 1 to 3 heteroatoms selected from O, N, and S provided said hydrophobic substituent has at least 6 carbon atoms.

[001109] In some embodiments, a polyamine derivative which is useful herein as delivery vehicle for polyanions is a polyalkylenimine (e.g., polyethylenimine) derivative having one or more carboxyalkyl substituents comprising from 6 to 40 carbon atoms, and one or more hydrophobic substituents selected from hydrocarbon substituents having at least 2 carbon atoms, preferably from 6 to 40 carbon atoms, wherein each of said hydrophobic substituents may be or may comprise an alkyl group and/or each of said hydrophobic substituents may be or may comprise an aryl group.

[001110] In some embodiments, the polyamine derivative has (i) a linear polyethylenimine moiety of from 2 to 500 kDa (in terms of number average molecular weight), or (ii) a branched polyethylenimine moiety of from 0.5 to 200 kDa (in terms of number average molecular weight); and the carboxylated substituents have from 10 to 16 carbon atoms and are n-alkylcarboxylic acids and the hydrophobic substituents have from 1 to 12 carbon atoms and are alkyls, preferably n-alkyls, and/or alkylarylalkyls. Other suitable polymers include, for example, Viromer® and jetPEI® (Polyplus). Other suitable polymers or lipidoids useful for delivery of nucleic acids, such as RNA, are described in WO 2014/207231, WO 2016/097377 and WO 2024/042236, all of which are incorporated herein by reference in their entirety. Other delivery systems suitable for nucleic acid (e.g., RNA) delivery, which are based on oligosaccharide compounds, are described in WO 2023/067121, WO 2023/067123, WO 2023/067124, WO 2023/067125, and WO 2023/067126, all of which are incorporated herein by reference in their entirety.

RNA Targeting

[OOllll] Some aspects of the present disclosure involve the targeted delivery of the RNA disclosed herein (e.g., RNA encoding vaccine antigens and/or immunostimulants).

[001112] In one embodiment, the present disclosure involves targeting lung. Targeting lung is in particular preferred if the RNA administered is RNA encoding vaccine antigen. RNA may be delivered to lung, for example, by administering the RNA which may be formulated as particles as described herein, e.g., lipid particles, by inhalation.

[001113] In one embodiment, the present disclosure involves targeting the lymphatic system, in particular secondary lymphoid organs, more specifically spleen. Targeting the lymphatic system, in particular secondary lymphoid organs, more specifically spleen is in particular preferred if the RNA administered is RNA encoding vaccine antigen.

[001114] In one embodiment, the target cell is a spleen cell. In one embodiment, the target cell is an antigen presenting cell such as a professional antigen presenting cell in the spleen. In one embodiment, the target cell is a dendritic cell in the spleen.

[001115] The "lymphatic system" is part of the circulatory system and an important part of the immune system, comprising a network of lymphatic vessels that carry lymph. The lymphatic system consists of lymphatic organs, a conducting network of lymphatic vessels, and the circulating lymph. The primary or central lymphoid organs generate lymphocytes from immature progenitor cells. The thymus and the bone marrow constitute the primary lymphoid organs. Secondary or peripheral lymphoid organs, which include lymph nodes and the spleen, maintain mature naive lymphocytes and initiate an adaptive immune response.

[001116] RNA may be delivered to spleen by so-called lipoplex formulations, in which the RNA is bound to liposomes comprising a cationic lipid and optionally an additional or helper lipid to form injectable nanoparticle formulations. The liposomes may be obtained by injecting a solution of the lipids in ethanol into water or a suitable aqueous phase. RNA lipoplex particles may be prepared by mixing the liposomes with RNA. Spleen targeting RNA lipoplex particles are described in WO 2013/143683, herein incorporated by reference. It has been found that RNA lipoplex particles having a net negative charge may be used to preferentially target spleen tissue or spleen cells such as antigen-presenting cells, in particular dendritic cells. Accordingly, following administration of the RNA lipoplex particles, RNA accumulation and/or RNA expression in the spleen occurs. Thus, RNA lipoplex particles of the present disclosure may be used for expressing RNA in the spleen. In an embodiment, after administration of the RNA lipoplex particles, no or essentially no RNA accumulation and/or RNA expression in the lung and/or liver occurs. In one embodiment, after administration of the RNA lipoplex particles, RNA accumulation and/or RNA expression in antigen presenting cells, such as professional antigen presenting cells in the spleen occurs. Thus, RNA lipoplex particles of the present disclosure may be used for expressing RNA in such antigen presenting cells. In one embodiment, the antigen presenting cells are dendritic cells and/or macrophages.

[001117] The electric charge of the RNA lipoplex particles of the present disclosure is the sum of the electric charges present in the at least one cationic lipid and the electric charges present in the RNA. The charge ratio is the ratio of the positive charges present in the at least one cationic lipid to the negative charges present in the RNA. The charge ratio of the positive charges present in the at least one cationic lipid to the negative charges present in the RNA is calculated by the following equation: charge ratio= [(cationic lipid concentration (mol)) * (the total number of positive charges in the cationic lipid)] / [(RNA concentration (mol)) * (the total number of negative charges in RNA)].

[001118] The spleen targeting RNA lipoplex particles described herein at physiological pH preferably have a net negative charge such as a charge ratio of positive charges to negative charges from about 1.9:2 to about 1:2, or about 1.6:2 to about 1:2, or about 1.6:2 to about 1.1:2. In specific embodiments, the charge ratio of positive charges to negative charges in the RNA lipoplex particles at physiological pH is about 1.9:2.0, about 1.8:2.0, about 1.7:2.0, about 1.6:2.0, about 1.5:2.0, about 1.4:2.0, about 1.3:2.0, about 1.2:2.0, about 1.1:2.0, or about 1:2.0.

[001119] Immunostimulants may be provided to a subject by administering to the subject RNA encoding an immunostimulant in a formulation for preferential delivery of RNA to liver or liver tissue. The delivery of RNA to such target organ or tissue is preferred, in particular, if it is desired to express large amounts of the immunostimulant and/or if systemic presence of the immunostimulant, in particular in significant amounts, is desired or required.

[001120] RNA delivery systems have an inherent preference to the liver. This pertains to lipid-based particles, cationic and neutral nanoparticles, in particular lipid nanoparticles such as liposomes, nanomicelles and lipophilic ligands in bioconjugates. Liver accumulation is caused by the discontinuous nature of the hepatic vasculature or the lipid metabolism (liposomes and lipid or cholesterol conjugates).

[001121] For in vivo delivery of RNA to the liver, a drug delivery system may be used to transport the RNA into the liver by preventing its degradation. For example, polyplex nanomicelles consisting of a polyethylene glycol) (PEG)-coated surface and an RNA (e.g., mRNA)-containing core is a useful system because the nanomicelles provide excellent in vivo stability of the RNA, under physiological conditions. Furthermore, the stealth property provided by the polyplex nanomicelle surface, composed of dense PEG palisades, effectively evades host immune defenses.

[001122] Examples of suitable immunostimulants for targeting liver are cytokines involved in T cell proliferation and/or maintenance. Examples of suitable cytokines include IL2 or IL7, fragments and variants thereof, and fusion proteins of these cytokines, fragments and variants, such as extended-PK cytokines. [001123] In another embodiment, RNA encoding an immunostimulant may be administered in a formulation for preferential delivery of RNA to the lymphatic system, in particular secondary lymphoid organs, more specifically spleen. The delivery of an immunostimulant to such target tissue is preferred, in particular, if presence of the immunostimulant in this organ or tissue is desired (e.g., for inducing an immune response, in particular in case immunostimulants such as cytokines are required during T-cell priming or for activation of resident immune cells), while it is not desired that the immunostimulant is present systemically, in particular in significant amounts (e.g., because the immunostimulant has systemic toxicity).

[001124] Examples of suitable immunostimulants are cytokines involved in T cell priming. Examples of suitable cytokines include IL12, IL15, IFN-a, or IFN-(3, fragments and variants thereof, and fusion proteins of these cytokines, fragments and variants, such as extended-PK cytokines.

Multivalent Vaccines

[001125] In some embodiments, compositions described herein are multivalent compositions, comprising two or more antigens from different coronaviruses (e.g., different betacoronaviruses, different sarbecovi ruses, or different SARS-CoV-2 variants). Without wishing to be bound by theory, the present disclosure provides an insight that administering to a subject a composition that delivers a plurality of antigens, each from a different infectious agent (e.g., coronavirus species or SARS-CoV-2 variant), can induce an immune response directed to epitopes that are shared by each of the delivered antigens, thus inducing a neutralization response that is more broadly neutralizing as compared to a composition that delivers fewer antigens. In some embodiments, a more broadly cross-neutralizing response is observed for two or more mRNAs encapsulated in the same delivery vehicle as compared to the same two or more mRNAs delivered in separate delivery vehicles. In some embodiments, the different coronavirus strains are selected so that the shared epitopes comprise neutralizing epitopes. In some embodiments, the shared neutralizing epitopes are present in a number of coronavirus antigens and/or SARS- CoV-2 species. In some embodiments, the different coronavirus strains are selected so as to have minimal overlapping non-neutralizing epitopes. In some embodiments, the different coronavirus strains are selected so as to be evolutionary distinct from one another. In some embodiments, a multivalent composition comprises one or more antigens (e.g., Spike protein, or a fragment thereof, including, e.g., a truncated SI subdomain or RBD) from SARS-CoV-2 Omicron BA.l or a descendent thereof and one or more antigens (e.g., Spike protein, or a fragment thereof, including, e.g., a truncated SI subdomain or RBD) from SARS-CoV-2 Omicron BA.4/5 or a descendent thereof.

[001126] In some embodiments, compositions described herein deliver 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more antigens, each from a different coronavirus (e.g., SARS-CoV-2) strain or variant.

Immunostimulants

[001127] In one embodiment, the RNA encoding vaccine antigen may be non-immunogenic. In this and other embodiments, the RNA encoding vaccine antigen may be co-administered with an immunostimulant or RNA encoding an immunostimulant. The methods and agents described herein are particularly effective if the immunostimulant is attached to a pharmacokinetic modifying group (hereafter referred to as "extended- pharmacokinetic (PK)" immunostimulant). The methods and agents described herein are particularly effective if the immunostimulant is administered in the form of RNA encoding an immunostimulant. In one embodiment, said RNA is targeted to the liver for systemic availability. Liver cells can be efficiently transfected and are able to produce large amounts of protein.

[001128] An "immunostimulant" is any substance that stimulates the immune system by inducing activation or increasing activity of any of the immune system's components, in particular immune effector cells. The immunostimulant may be pro-inflammatory.

[001129] According to one aspect, the immunostimulant is a cytokine or a variant thereof. Examples of cytokines include interferons, such as interferon-alpha (IFN-o) or interferon-gamma (IFN-y), interleukins, such as IL2, IL7, IL12, IL15 and IL23, colony stimulating factors, such as M-CSF and GM-CSF, and tumor necrosis factor. According to another aspect, the immunostimulant includes an adjuvant-type immunostimulatory agent such as APC Toll-like Receptor agonists or costimulatory/cell adhesion membrane proteins. Examples of Toll-like Receptor agonists include costimulatory/adhesion proteins such as CD80, CD86, and ICAM-1.

[001130] Cytokines are a category of small proteins (~5-20 kDa) that are important in cell signaling. Their release has an effect on the behavior of cells around them. Cytokines are involved in autocrine signaling, paracrine signaling and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors but generally not hormones or growth factors (despite some overlap in the terminology). Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells. A given cytokine may be produced by more than one type of cell. Cytokines act through receptors, and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines in complex ways.

[001131] According to the present disclosure, a cytokine may be a naturally occurring cytokine or a functional fragment or variant thereof. A cytokine may be human cytokine and may be derived from any vertebrate, especially any mammal. One particularly preferred cytokine is interferon-a.

Interferons

[001132] Interferons (IFNs) are a group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

[001133] Based on the type of receptor through which they signal, interferons are typically divided among three classes: type I interferon, type II interferon, and type III interferon.

[001134] All type I interferons bind to a specific cell surface receptor complex known as the IFN-a/|3 receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains.

[001135] The type I interferons present in humans are IFNa, IFNfJ, IFNE, IFNK and IFNco. In general, type I interferons are produced when the body recognizes a virus that has invaded it. They are produced by fibroblasts and monocytes. Once released, type I interferons bind to specific receptors on target cells, which leads to expression of proteins that will prevent the virus from producing and replicating its RNA and DNA.

[001136] The IFNa proteins are produced mainly by plasmacytoid dendritic cells (pDCs). They are mainly involved in innate immunity against viral infection. The genes responsible for their synthesis come in 13 subtypes that are called IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21. These genes are found together in a cluster on chromosome 9. [001137] The IFN[3 proteins are produced in large quantities by fibroblasts. They have antiviral activity that is involved mainly in innate immune response. Two types of IFN(3 have been described, IFN(31 and IFN03. The natural and recombinant forms of IFNpi have antiviral, antibacterial, and anticancer properties.

[001138] Type II interferon (IFNy in humans) is also known as immune interferon and is activated by IL12. Furthermore, type II interferons are released by cytotoxic T cells and T helper cells.

[001139] Type III interferons signal through a receptor complex consisting of IL10R2 (also called CRF2-4) and IFNLR1 (also called CRF2-12). Although discovered more recently than type I and type II IFNs, recent information demonstrates the importance of type III IFNs in some types of virus or fungal infections.

[001140] In general, type I and II interferons are responsible for regulating and activating the immune response.

[001141] According to the present disclosure, a type I interferon is preferably IFNa or IFN[3, more preferably IFNa.

[001142] According to the present disclosure, an interferon may be a naturally occurring interferon or a functional fragment or variant thereof. An interferon may be human interferon and may be derived from any vertebrate, especially any mammal.

Interleukins

[001143] Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that can be divided into four major groups based on distinguishing structural features. However, their amino acid sequence similarity is rather weak (typically 15-25% identity). The human genome encodes more than 50 interleukins and related proteins.

[001144] According to the present disclosure, an interleukin may be a naturally occurring interleukin or a functional fragment or variant thereof. An interleukin may be human interleukin and may be derived from any vertebrate, especially any mammal.

Extended-PK group

[001145] Immunostimulant polypeptides described herein can be prepared as fusion or chimeric polypeptides that include an immunostimulant portion and a heterologous polypeptide (i.e., a polypeptide that is not an immunostimulant). The immunostimulant may be fused to an extended-PK group, which increases circulation half-life. Non-limiting examples of extended-PK groups are described infra. It should be understood that other PK groups that increase the circulation half-life of immunostimulants such as cytokines, or variants thereof, are also applicable to the present disclosure. In certain embodiments, the extended-PK group is a serum albumin domain (e.g., mouse serum albumin, human serum albumin).

[001146] As used herein, the term "PK" is an acronym for "pharmacokinetic" and encompasses properties of a compound including, by way of example, absorption, distribution, metabolism, and elimination by a subject. As used herein, an "extended-PK group" refers to a protein, peptide, or moiety that increases the circulation half-life of a biologically active molecule when fused to or administered together with the biologically active molecule. Examples of an extended-PK group include serum albumin (e.g., HSA), Immunoglobulin Fc or Fc fragments and variants thereof, transferrin and variants thereof, and human serum albumin (HSA) binders (as disclosed in U.S. Publication Nos. 2005/0287153 and 2007/0003549). Other exemplary extended-PK groups are disclosed in Kontermann, Expert Opin Biol Ther, 2016 Jul; 16(7):903-15 which is herein incorporated by reference in its entirety. As used herein, an "extended-PK" immunostimulant refers to an immunostimulant moiety in combination with an extended-PK group. In one embodiment, the extended-PK immunostimulant is a fusion protein in which an immunostimulant moiety is linked or fused to an extended-PK group. [001147] In certain embodiments, the serum half-life of an extended-PK immunostimulant is increased relative to the immunostimulant alone (i.e., the immunostimulant not fused to an extended-PK group). In certain embodiments, the serum half-life of the extended-PK immunostimulant is at least 20, 40, 60, 80, 100, 120, 150, 180, 200, 400, 600, 800, or 1000% longer relative to the serum half-life of the immunostimulant alone. In certain embodiments, the serum half-life of the extended-PK immunostimulant is at least 1.5-fold, 2-fold, 2.5-fold, 3-fold, 3.5 fold, 4-fold, 4.5-fold, 5-fold, 6-fold, 7-fold, 8-fold, 10- fold, 12-fold, 13-fold, 15-fold, 17-fold, 20-fold, 22- fold, 25-fold, 27-fold, 30-fold, 35-fold, 40-fold, or 50-fold greater than the serum half-life of the immunostimulant alone. In certain embodiments, the serum half-life of the extended-PK immunostimulant is at least 10 hours, 15 hours, 20 hours, 25 hours, 30 hours, 35 hours, 40 hours, 50 hours, 60 hours, 70 hours, 80 hours, 90 hours, 100 hours, 110 hours, 120 hours, 130 hours, 135 hours, 140 hours, 150 hours, 160 hours, or 200 hours.

[001148] As used herein, "half-life" refers to the time taken for the serum or plasma concentration of a compound such as a peptide or protein to reduce by 50%, in vivo, for example due to degradation and/or clearance or sequestration by natural mechanisms. An extended-PK immunostimulant suitable for use herein is stabilized in vivo and its half-life increased by, e.g., fusion to serum albumin (e.g., HSA or MSA), which resist degradation and/or clearance or sequestration. The half-life can be determined in any manner known per se, such as by pharmacokinetic analysis. Suitable techniques will be clear to the person skilled in the art, and may for example generally involve the steps of suitably administering a suitable dose of the amino acid sequence or compound to a subject; collecting blood samples or other samples from said subject at regular intervals; determining the level or concentration of the amino acid sequence or compound in said blood sample; and calculating, from (a plot of) the data thus obtained, the time until the level or concentration of the amino acid sequence or compound has been reduced by 50% compared to the initial level upon dosing. Further details are provided in, e.g., standard handbooks, such as Kenneth, A. et al., Chemical Stability of Pharmaceuticals: A Handbook for Pharmacists and in Peters et al., Pharmacokinetic Analysis: A Practical Approach (1996). Reference is also made to Gibaldi, M. et al., Pharmacokinetics, 2nd Rev. Edition, Marcel Dekker (1982).

[001149] In certain embodiments, the extended-PK group includes serum albumin, or fragments thereof or variants of the serum albumin or fragments thereof (all of which for the purpose of the present disclosure are comprised by the term "albumin"). Polypeptides described herein may be fused to albumin (or a fragment or variant thereof) to form albumin fusion proteins. Such albumin fusion proteins are described in U.S. Publication No. 20070048282.

[001150] As used herein, "albumin fusion protein" refers to a protein formed by the fusion of at least one molecule of albumin (or a fragment or variant thereof) to at least one molecule of a protein such as a therapeutic protein, in particular an immunostimulant. The albumin fusion protein may be generated by translation of a nucleic acid in which a polynucleotide encoding a therapeutic protein is joined in-frame with a polynucleotide encoding an albumin. The therapeutic protein and albumin, once part of the albumin fusion protein, may each be referred to as a "portion", "region" or "moiety" of the albumin fusion protein (e.g., a "therapeutic protein portion" or an "albumin protein portion"). In a highly preferred embodiment, an albumin fusion protein comprises at least one molecule of a therapeutic protein (including, but not limited to a mature form of the therapeutic protein) and at least one molecule of albumin (including but not limited to a mature form of albumin). In one embodiment, an albumin fusion protein is processed by a host cell such as a cell of the target organ for administered RNA, e.g. a liver cell, and secreted into the circulation. Processing of the nascent albumin fusion protein that occurs in the secretory pathways of the host cell used for expression of the RNA may include, but is not limited to signal peptide cleavage; formation of disulfide bonds; proper folding; addition and processing of carbohydrates (such as for example, N- and O-linked glycosylation); specific proteolytic cleavages; and/or assembly into multimeric proteins. An albumin fusion protein is preferably encoded by RNA in a non-processed form which in particular has a signal peptide at its N-terminus and following secretion by a cell is preferably present in the processed form wherein in particular the signal peptide has been cleaved off. In a most preferred embodiment, the "processed form of an albumin fusion protein" refers to an albumin fusion protein product which has undergone N-terminal signal peptide cleavage, herein also referred to as a "mature albumin fusion protein".

[001151] In preferred embodiments, albumin fusion proteins comprising a therapeutic protein have a higher plasma stability compared to the plasma stability of the same therapeutic protein when not fused to albumin. Plasma stability typically refers to the time period between when the therapeutic protein is administered in vivo and carried into the bloodstream and when the therapeutic protein is degraded and cleared from the bloodstream, into an organ, such as the kidney or liver, that ultimately clears the therapeutic protein from the body. Plasma stability is calculated in terms of the half-life of the therapeutic protein in the bloodstream. The half-life of the therapeutic protein in the bloodstream can be readily determined by common assays known in the art.

[001152] As used herein, "albumin" refers collectively to albumin protein or amino acid sequence, or an albumin fragment or variant, having one or more functional activities (e.g., biological activities) of albumin. In particular, "albumin" refers to human albumin or fragments or variants thereof especially the mature form of human albumin, or albumin from other vertebrates or fragments thereof, or variants of these molecules. The albumin may be derived from any vertebrate, especially any mammal, for example human, cow, sheep, or pig. Non-mammalian albumins include, but are not limited to, hen and salmon. The albumin portion of the albumin fusion protein may be from a different animal than the therapeutic protein portion.

[001153] In certain embodiments, the albumin is human serum albumin (HSA), or fragments or variants thereof, such as those disclosed in US 5,876,969, WO 2011/124718, WO 2013/075066, and WO 2011/0514789. [001154] The terms, human serum albumin (HSA) and human albumin (HA) are used interchangeably herein. The terms, "albumin and "serum albumin" are broader, and encompass human serum albumin (and fragments and variants thereof) as well as albumin from other species (and fragments and variants thereof).

[001155] As used herein, a fragment of albumin sufficient to prolong the therapeutic activity or plasma stability of the therapeutic protein refers to a fragment of albumin sufficient in length or structure to stabilize or prolong the therapeutic activity or plasma stability of the protein so that the plasma stability of the therapeutic protein portion of the albumin fusion protein is prolonged or extended compared to the plasma stability in the non-fusion state.

[001156] The albumin portion of the albumin fusion proteins may comprise the full length of the albumin sequence, or may include one or more fragments thereof that are capable of stabilizing or prolonging the therapeutic activity or plasma stability. Such fragments may be of 10 or more amino acids in length or may include about 15, 20, 25, 30, 50, or more contiguous amino acids from the albumin sequence or may include part or all of specific domains of albumin. For instance, one or more fragments of HSA spanning the first two immunoglobulin-like domains may be used. In a preferred embodiment, the HSA fragment is the mature form of HSA.

[001157] Generally speaking, an albumin fragment or variant will be at least 100 amino acids long, preferably at least 150 amino acids long.

[001158] According to the present disclosure, albumin may be naturally occurring albumin or a fragment or variant thereof. Albumin may be human albumin and may be derived from any vertebrate, especially any mammal.

[001159] Preferably, the albumin fusion protein comprises albumin as the N-terminal portion, and a therapeutic protein as the C-terminal portion. Alternatively, an albumin fusion protein comprising albumin as the C-terminal portion, and a therapeutic protein as the N-terminal portion may also be used. In other embodiments, the albumin fusion protein has a therapeutic protein fused to both the N-terminus and the C-terminus of albumin. In a preferred embodiment, the therapeutic proteins fused at the N- and C-termini are the same therapeutic proteins. In another preferred embodiment, the therapeutic proteins fused at the N- and C-termini are different therapeutic proteins. In one embodiment, the different therapeutic proteins are both cytokines.

[001160] In one embodiment, the therapeutic protein(s) is (are) joined to the albumin through (a) peptide linker(s). A linker peptide between the fused portions may provide greater physical separation between the moieties and thus maximize the accessibility of the therapeutic protein portion, for instance, for binding to its cognate receptor. The linker peptide may consist of amino acids such that it is flexible or more rigid. The linker sequence may be cleavable by a protease or chemically.

[001161] As used herein, the term "Fc region" refers to the portion of a native immunoglobulin formed by the respective Fc domains (or Fc moieties) of its two heavy chains. As used herein, the term "Fc domain" refers to a portion or fragment of a single immunoglobulin (Ig) heavy chain wherein the Fc domain does not comprise an Fv domain. In certain embodiments, an Fc domain begins in the hinge region just upstream of the papain cleavage site and ends at the C-terminus of the antibody. Accordingly, a complete Fc domain comprises at least a hinge domain, a CH2 domain, and a CH3 domain. In certain embodiments, an Fc domain comprises at least one of: a hinge (e.g., upper, middle, and/or lower hinge region) domain, a CH2 domain, a CH3 domain, a CHA domain, or a variant, portion, or fragment thereof. In certain embodiments, an Fc domain comprises a complete Fc domain (i.e., a hinge domain, a CH2 domain, and a CH3 domain). In certain embodiments, an Fc domain comprises a hinge domain (or portion thereof) fused to a CH3 domain (or portion thereof). In certain embodiments, an Fc domain comprises a CH2 domain (or portion thereof) fused to a CH3 domain (or portion thereof). In certain embodiments, an Fc domain consists of a CH3 domain or portion thereof. In certain embodiments, an Fc domain consists of a hinge domain (or portion thereof) and a CH3 domain (or portion thereof). In certain embodiments, an Fc domain consists of a CH2 domain (or portion thereof) and a CH3 domain. In certain embodiments, an Fc domain consists of a hinge domain (or portion thereof) and a CH2 domain (or portion thereof). In certain embodiments, an Fc domain lacks at least a portion of a CH2 domain (e.g., all or part of a CH2 domain). An Fc domain herein generally refers to a polypeptide comprising all or part of the Fc domain of an immunoglobulin heavy-chain. This includes, but is not limited to, polypeptides comprising the entire CHI, hinge, CH2, and/or CH3 domains as well as fragments of such peptides comprising only, e.g., the hinge, CH2, and CH3 domain. The Fc domain may be derived from an immunoglobulin of any species and/or any subtype, including, but not limited to, a human IgGl, IgG2, IgG3, IgGA, IgD, IgA, IgE, or IgM antibody. The Fc domain encompasses native Fc and Fc variant molecules. As set forth herein, it will be understood by one of ordinary skill in the art that any Fc domain may be modified such that it varies in amino acid sequence from the native Fc domain of a naturally occurring immunoglobulin molecule. In certain embodiments, the Fc domain has reduced effector function (e.g., FcyR binding).

[001162] The Fc domains of a polypeptide described herein may be derived from different immunoglobulin molecules. For example, an Fc domain of a polypeptide may comprise a CH2 and/or CH3 domain derived from an IgGl molecule and a hinge region derived from an IgG3 molecule. In another example, an Fc domain can comprise a chimeric hinge region derived, in part, from an IgGl molecule and, in part, from an IgG3 molecule. In another example, an Fc domain can comprise a chimeric hinge derived, in part, from an IgGl molecule and, in part, from an IgGA molecule.

[001163] In certain embodiments, an extended-PK group includes an Fc domain or fragments thereof or variants of the Fc domain or fragments thereof (all of which for the purpose of the present disclosure are comprised by the term "Fc domain"). The Fc domain does not contain a variable region that binds to antigen. Fc domains suitable for use in the present disclosure may be obtained from a number of different sources. In certain embodiments, an Fc domain is derived from a human immunoglobulin. In certain embodiments, the Fc domain is from a human IgGl constant region. It is understood, however, that the Fc domain may be derived from an immunoglobulin of another mammalian species, including for example, a rodent (e.g. a mouse, rat, rabbit, guinea pig) or non- human primate (e.g. chimpanzee, macaque) species.

[001164] Moreover, the Fc domain (or a fragment or variant thereof) may be derived from any immunoglobulin class, including IgM, IgG, IgD, IgA, and IgE, and any immunoglobulin isotype, including IgGl, IgG2, IgG3, and IgG4.

[001165] A variety of Fc domain gene sequences (e.g., mouse and human constant region gene sequences) are available in the form of publicly accessible deposits. Constant region domains comprising an Fc domain sequence can be selected lacking a particular effector function and/or with a particular modification to reduce immunogenicity. Many sequences of antibodies and antibody-encoding genes have been published and suitable Fc domain sequences (e.g. hinge, CH2, and/or CH3 sequences, or fragments or variants thereof) can be derived from these sequences using art recognized techniques.

[001166] In certain embodiments, the extended-PK group is a serum albumin binding protein such as those described in US2005/0287153, US2007/0003549, US2007/0178082, US2007/0269422, US2010/0113339, W02009/083804, and W02009/133208, which are herein incorporated by reference in their entirety. In certain embodiments, the extended-PK group is transferrin, as disclosed in US 7,176,278 and US 8,158,579, which are herein incorporated by reference in their entirety. In certain embodiments, the extended-PK group is a serum immunoglobulin binding protein such as those disclosed in US2007/0178082, US2014/0220017, and US2017/0145062, which are herein incorporated by reference in their entirety. In certain embodiments, the extended-PK group is a fibronectin (Fn)-based scaffold domain protein that binds to serum albumin, such as those disclosed in US2012/0094909, which is herein incorporated by reference in its entirety. Methods of making fibronectin-based scaffold domain proteins are also disclosed in US2012/0094909. A non-limiting example of a Fn3-based extended-PK group is Fn3(HSA), i.e., a Fn3 protein that binds to human serum albumin.

[001167] In certain aspects, the extended-PK immunostimulant, suitable for use according to the present disclosure, can employ one or more peptide linkers. As used herein, the term "peptide linker" refers to a peptide or polypeptide sequence which connects two or more domains (e.g., the extended-PK moiety and an immunostimulant moiety) in a linear amino acid sequence of a polypeptide chain. For example, peptide linkers may be used to connect an immunostimulant moiety to a HSA domain.

[001168] Linkers suitable for fusing the extended-PK group to e.g. an immunostimulant are well known in the art. Exemplary linkers include glycine-serine-polypeptide linkers, glycine-proline-polypeptide linkers, and prolinealanine polypeptide linkers. In certain embodiments, the linker is a glycine-serine-polypeptide linker, i.e., a peptide that consists of glycine and serine residues.

[001169] In addition to, or in place of, the heterologous polypeptides described above, an immunostimulant polypeptide described herein can contain sequences encoding a "marker" or "reporter". Examples of marker or reporter genes include p-lactamase, chloramphenicol acetyltransferase (CAT), adenosine deaminase (ADA), aminoglycoside phosphotransferase, dihydrofolate reductase (DHFR), hygromycin-B-hosphotransferase (HPH), thymidine kinase (TK), |3-galactosidase, and xanthine guanine phosphoribosyltransferase (XGPRT).

Pharmaceutical compositions

[001170] The agents described herein may be administered in pharmaceutical compositions or medicaments and may be administered in the form of any suitable pharmaceutical composition. [001171] In one embodiment, the pharmaceutical composition described herein is an immunogenic composition for inducing an immune response against coronavirus in a subject. For example, in one embodiment, the immunogenic composition is a vaccine.

[001172] In one embodiment of all aspects of the present disclosure, the components described herein such as RNA encoding a vaccine antigen may be administered in a pharmaceutical composition which may comprise a pharmaceutically acceptable carrier and may optionally comprise one or more adjuvants, stabilizers etc. In one embodiment, the pharmaceutical composition is for therapeutic or prophylactic treatments, e.g., for use in treating or preventing a coronavirus infection.

[001173] The term "pharmaceutical composition" relates to a formulation comprising a therapeutically effective agent, preferably together with pharmaceutically acceptable carriers, diluents and/or excipients. Said pharmaceutical composition is useful for treating, preventing, or reducing the severity of a disease or disorder by administration of said pharmaceutical composition to a subject. A pharmaceutical composition is also known in the art as a pharmaceutical formulation.

[001174] The pharmaceutical compositions of the present disclosure may comprise one or more adjuvants or may be administered with one or more adjuvants. The term "adjuvant" relates to a compound which prolongs, enhances or accelerates an immune response. Adjuvants comprise a heterogeneous group of compounds such as oil emulsions (e.g., Freund's adjuvants), mineral compounds (such as alum), bacterial products (such as Bordetella pertussis toxin), or immune-stimulating complexes. Examples of adjuvants include, without limitation, LPS, GP96, CpG oligodeoxynucleotides, growth factors, and cytokines, such as monokines, lymphokines, interleukins, chemokines. The cytokines may be IL1, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9, IL10, IL12, IFNa, IFNy, GM-CSF, LT-a. Further known adjuvants are aluminium hydroxide, Freund's adjuvant or oil such as Montanide® ISA51. Other suitable adjuvants for use in the present disclosure include lipopeptides, such as Pam3Cys.

[001175] The pharmaceutical compositions according to the present disclosure are generally applied in a "pharmaceutically effective amount" and in "a pharmaceutically acceptable preparation".

[001176] The term "pharmaceutically acceptable" refers to the non-toxicity of a material which does not interact with the action of the active component of the pharmaceutical composition.

[001177] The term "pharmaceutically effective amount" or "therapeutically effective amount" refers to the amount which achieves a desired reaction or a desired effect alone or together with further doses. In the case of the treatment of a particular disease, the desired reaction preferably relates to inhibition of the course of the disease. This comprises slowing down the progress of the disease and, in particular, interrupting or reversing the progress of the disease. The desired reaction in a treatment of a disease may also be delay of the onset or a prevention of the onset of said disease or said condition. An effective amount of the compositions described herein will depend on the condition to be treated, the severeness of the disease, the individual parameters of the patient, including age, physiological condition, size and weight, the duration of treatment, the type of an accompanying therapy (if present), the specific route of administration and similar factors. Accordingly, the doses administered of the compositions described herein may depend on various of such parameters. In the case that a reaction in a patient is insufficient with an initial dose, higher doses (or effectively higher doses achieved by a different, more localized route of administration) may be used.

[001178] The pharmaceutical compositions of the present disclosure may contain salts, buffers, preservatives, and optionally other therapeutic agents. In one embodiment, the pharmaceutical compositions of the present disclosure comprise one or more pharmaceutically acceptable carriers, diluents and/or excipients.

[001179] Suitable preservatives for use in the pharmaceutical compositions of the present disclosure include, without limitation, benzalkonium chloride, chlorobutanol, paraben and thimerosal. [001180] The term "excipient" as used herein refers to a substance which may be present in a pharmaceutical composition of the present disclosure but is not an active ingredient. Examples of excipients, include without limitation, carriers, binders, diluents, lubricants, thickeners, surface active agents, preservatives, stabilizers, emulsifiers, buffers, flavoring agents, or colorants.

[001181] The term "diluent" relates a diluting and/or thinning agent. Moreover, the term "diluent" includes any one or more of fluid, liquid or solid suspension and/or mixing media. Examples of suitable diluents include ethanol, glycerol and water.

[001182] The term "carrier" refers to a component which may be natural, synthetic, organic, inorganic in which the active component is combined in order to facilitate, enhance or enable administration of the pharmaceutical composition. A carrier as used herein may be one or more compatible solid or liquid fillers, diluents or encapsulating substances, which are suitable for administration to subject. Suitable carrier include, without limitation, sterile water, Ringer, Ringer lactate, sterile sodium chloride solution, isotonic saline, polyalkylene glycols, hydrogenated naphthalenes and, in particular, biocompatible lactide polymers, lactide/glycolide copolymers or polyoxyethylene/polyoxy-propylene copolymers. In one embodiment, the pharmaceutical composition of the present disclosure includes isotonic saline.

[001183] Pharmaceutically acceptable carriers, excipients or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R Gennaro edit. 1985).

[001184] Pharmaceutical carriers, excipients or diluents can be selected with regard to the intended route of administration and standard pharmaceutical practice.

[001185] In one embodiment, pharmaceutical compositions described herein may be administered intravenously, intraarterially, subcutaneously, intradermally or intramuscularly. In certain embodiments, the pharmaceutical composition is formulated for local administration or systemic administration. Systemic administration may include enteral administration, which involves absorption through the gastrointestinal tract, or parenteral administration. As used herein, "parenteral administration" refers to the administration in any manner other than through the gastrointestinal tract, such as by intravenous injection. In a preferred embodiment, the pharmaceutical composition is formulated for intramuscular administration. In another embodiment, the pharmaceutical composition is formulated for systemic administration, e.g., for intravenous administration. [001186] The term "co-administering" as used herein means a process whereby different compounds or compositions (e.g., RNA encoding an antigen and RNA encoding an immunostimulant) are administered to the same patient. The different compounds or compositions may be administered simultaneously, at essentially the same time, or sequentially.

[001187] The pharmaceutical compositions and products described herein may be provided as a frozen concentrate for solution for injection, e.g., at a concentration of 0.50 mg/mL. In one embodiment, for preparation of solution for injection, a drug product is thawed and diluted with isotonic sodium chloride solution (e.g., 0.9% NaCI, saline), e.g., by a one-step dilution process. In some embodiments, bacteriostatic sodium chloride solution (e.g., 0.9% NaCI, saline) cannot be used as a diluent. In some embodiments, a diluted drug product is an off- white suspension. The concentration of the final solution for injection varies depending on the respective dose level to be administered.

[001188] In one embodiment, administration is performed within 6 h after begin of preparation due to the risk of microbial contamination and considering the multiple-dose approach of the preparation process. In one embodiment, in this period of 6 h, two conditions are allowed: room temperature for preparation, handling and transfer as well as 2 to 8°C for storage. [001189] Compositions described herein may be shipped and/or stored under temperature-controlled conditions, e.g., temperature conditions of about 4-5oC or below, about -20oC or below, - 70°C±10°C (e.g., - 80°C to -60°C), e.g., utilizing a cooling system (e.g., that may be or include dry ice) to maintain the desired temperature. In one embodiment, compositions described herein are shipped in temperature-controlled thermal shippers. Such shippers may contain a GPS-enabled thermal sensor to track the location and temperature of each shipment. The compositions can be stored by refilling with, e.g., dry ice.

Treatments

[001190] The present disclosure provides methods and agents for inducing an adaptive immune response against coronavirus in a subject comprising administering an effective amount of a composition comprising RNA encoding a coronavirus vaccine antigen described herein.

[001191] In one embodiment, the methods and agents described herein provide immunity in a subject to coronavirus, coronavirus infection, or to a disease or disorder associated with coronavirus. The present disclosure thus provides methods and agents for treating or preventing the infection, disease, or disorder associated with coronavirus.

[001192] In one embodiment, the methods and agents described herein are administered to a subject having an infection, disease, or disorder associated with coronavirus. In one embodiment, the methods and agents described herein are administered to a subject at risk for developing the infection, disease, or disorder associated with coronavirus. For example, the methods and agents described herein may be administered to a subject who is at risk for being in contact with coronavirus. In one embodiment, the methods and agents described herein are administered to a subject who lives in, traveled to, or is expected to travel to a geographic region in which coronavirus is prevalent. In one embodiment, the methods and agents described herein are administered to a subject who is in contact with or expected to be in contact with another person who lives in, traveled to, or is expected to travel to a geographic region in which coronavirus is prevalent. In one embodiment, the methods and agents described herein are administered to a subject who has knowingly been exposed to coronavirus through their occupation, or other contact. In one embodiment, a coronavirus is SARS-CoV-2. In some embodiments, methods and agents described herein are administered to a subject with evidence of prior exposure to and/or infection with SARS-CoV-2 and/or an antigen or epitope thereof or cross-reactive therewith. For example, in some embodiments, methods and agents described herein are administered to a subject in whom antibodies, B cells, and/or T cells reactive with one or more epitopes of a SARS-CoV-2 spike protein are detectable and/or have been detected.

[001193] For a composition to be useful as a vaccine, the composition must induce an immune response against the coronavirus antigen in a cell, tissue or subject (e.g., a human). In some embodiments, the composition induces an immune response against the coronavirus antigen in a cell, tissue or subject (e.g., a human). In some instances, the vaccine induces a protective immune response in a mammal. The therapeutic compounds or compositions of the present disclosure may be administered prophylactically (i.e., to prevent a disease or disorder) or therapeutically (i.e., to treat a disease or disorder) to subjects suffering from, or at risk of (or susceptible to) developing a disease or disorder. Such subjects may be identified using standard clinical methods. In the context of the present disclosure, prophylactic administration occurs prior to the manifestation of overt clinical symptoms of disease, such that a disease or disorder is prevented or alternatively delayed in its progression. In the context of the field of medicine, the term "prevent" encompasses any activity, which reduces the burden of mortality or morbidity from disease. Prevention can occur at primary, secondary and tertiary prevention levels. While primary prevention avoids the development of a disease, secondary and tertiary levels of prevention encompass activities aimed at preventing the progression of a disease and the emergence of symptoms as well as reducing the negative impact of an already established disease by restoring function and reducing disease-related complications.

[001194] The term "dose" as used herein refers in general to a "dose amount" which relates to the amount of RNA administered per administration, i.e., per dosing.

[001195] In some embodiments, administration of an immunogenic composition or vaccine of the present disclosure may be performed by single administration or boosted by multiple administrations.

[001196] In some embodiments, a regimen described herein includes at least one dose. In some embodiments, a regimen includes a first dose and at least one subsequent dose. In some embodiments, the first dose is the same amount as at least one subsequent dose. In some embodiments, the first dose is the same amount as all subsequent doses. In some embodiments, the first dose is a different amount as at least one subsequent dose. In some embodiments, the first dose is a different amount than all subsequent doses. In some embodiments, a regimen comprises two doses. In some embodiments, a provided regimen consists of two doses. In some embodiments, a regimen comprises three doses.

[001197] In one embodiment, the present disclosure envisions administration of a single dose. In one embodiment, the present disclosure envisions administration of a priming dose followed by one or more booster doses. The booster dose or the first booster dose may be administered 7 to 28 days or 14 to 24 days following administration of the priming dose. In some embodiments, a first booster dose may be administered 1 week to 3 months (e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks) following administration of a priming dose. In some embodiments, a subsequent booster dose may be administered at least 1 week or longer, including, e.g., at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, or longer, following a preceding booster dose. In some embodiments, subsequent booster doses may be administered about 5-9 weeks or 6-8 weeks apart. In some embodiments, at least one subsequent booster dose (e.g., after a first booster dose) may be administered at least 3 months or longer, including, e.g., at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, or longer, following a preceding dose.

[001198] In some embodiments, a subsequent dose given to an individual (e.g., as part of a primary regimen or booster regimen) can have the same amount of RNA as previously given to the individual. In some embodiments, a subsequent dose given to an individual (e.g., as part of a primary regimen or booster regimen) can differ in the amount of RNA, as compared to the amount previously given to the individual. For example, in some embodiments, a subsequent dose can be higher or lower than the prior dose, for example, based on consideration of various factors, including, e.g., immunogenicity and/or reactogenicity induced by the prior dose, prevalence of the disease, etc. In some embodiments, a subsequent dose can be higher than a prior dose by at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or higher. In some embodiments, a subsequent dose can be higher than a prior dose by at least 1.5-fold, at least 2-fold, at least 2.5 fold, at least 3-fold, or higher. In some embodiments, a subsequent dose can be higher than a prior dose by at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or higher. In some embodiments, a subsequent dose can be lower than a prior dose by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70% or lower.In some embodiments, an amount the RNA described herein from 0.1 μg to 300 pg, 0.5 μg to 200 pg, or 1 μg to 100 pg, such as about 1 pg, about 2 pg, about 3 pg, about 10 pg, about 15 pg, about 20 pg, about 25 pg, about 30 pg, about 35 pg, about 40 pg, about 45 pg, about 50 pg, about 55 pg, about 60 pg, about 70 pg, about 80 pg, about 90 pg, or about 100 pg may be administered per dose (e.g., in a given dose). [001199] In some embodiments, an amount of the RNA described herein of 60 μg or lower, 55 μg or lower, 50 μg or lower, 45 μg or lower, 40 μg or lower, 35 μg or lower, 30 μg or lower, 25 μg or lower, 20 μg or lower, 15 μg or lower, 10 μg or lower, 5 μg or lower, 3 μg or lower, 2.5 μg or lower, or 1 μg or lower may be administered per dose (e.g., in a given dose).

[001200] In some embodiments, an amount of the RNA described herein of at least 0.25 pg, at least 0.5 pg, at least 1 pg, at least 2 pg, at least 3 pg, at least 4 pg, at least 5 pg, at least 10 pg, at least 15 pg, at least 20 pg, at least 25 pg, at least 30 pg, at least 40 pg, at least 50 pg, or at least 60 μg may be administered per dose (e.g., in a given dose). In some embodiments, an amount of the RNA described herein of at least 3 ug may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of at least 10 ug may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of at least 15 ug may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of at least 20 ug may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of at least 25 ug may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of at least 30 ug may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of at least 50 ug may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of at least 60 ug may be administered in at least one of given doses. In some embodiments, combinations of aforementioned amounts may be administered in a regimen comprising two or more doses (e.g., a prior dose and a subsequent dose can be of different amounts as described herein). In some embodiments, combinations of aforementioned amounts may be administered in a primary regimen and a booster regimen (e.g., different doses can be given in a primary regimen and a booster regimen).

[001201] In some embodiments, a dose (e.g., a dose administered as part of a primary dosing regimen or a booster regimen) comprises about 30 μg of an RNA described herein. In some embodiments, a dose comprising about 30 μg of RNA described herein is administered to a subject who is 12 years or older.

[001202] In some embodiments, a dose (e.g., a dose administered as part of a primary dosing regimen or a booster regimen) comprises about 10 μg of an RNA described herein. In some embodiments, a dose comprising about 10 μg of RNA described herein is administered to a subject who is 5 years to less than 12 years old. [001203] In some embodiments, a dose (e.g., a dose administered as part of a primary dosing regimen or a booster regimen) comprises about 3 μg of an RNA described herein. In some embodiments, a dose comprising about 3 μg of RNA described herein is administered to a subject who is 6 months to less than 5 years old. [001204] In some embodiments, an amount of the RNA described herein of 0.25 μg to 60 pg, 0.5 μg to 55 pg, 1 μg to 50 pg, 5 μg to 40 pg, or 10 μg to 30 μg may be administered per dose. In some embodiments, an amount of the RNA described herein of 3 μg to 30 μg may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of 3 μg to 20 μg may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of 3 μg to 15 μg may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of 3 μg to 10 μg may be administered in at least one of given doses. In some embodiments, an amount of the RNA described herein of 10 μg to 30 μg may be administered in at least one of given doses.

[001205] In some embodiments, a regimen administered to a subject may comprise a plurality of doses (e.g., at least two doses, at least three doses, or more). In some embodiments, a regimen administered to a subject may comprise a first dose and a second dose, which are given at least 2 weeks apart, at least 3 weeks apart, at least 4 weeks apart, or more. In some embodiments, such doses may be at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, or more apart. In some embodiments, doses may be administered days apart, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 or more days apart. In some embodiments, doses may be administered about 1 to about 3 weeks apart, or about 1 to about 4 weeks apart, or about 1 to about 5 weeks apart, or about 1 to about 6 weeks apart, or about 1 to more than 6 weeks apart. In some embodiments, doses may be separated by a period of about 7 to about 60 days, such as for example about 14 to about 48 days, etc. In some embodiments, a minimum number of days between doses may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or more. In some embodiments, a maximum number of days between doses may be about 60, 59, 58, 57, 56, 55, 54, 53, 52, 51, 50, 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, or fewer. In some embodiments, doses may be about 21 to about 28 days apart. In some embodiments, doses may be about 19 to about 42 days apart. In some embodiments, doses may be about 7 to about 28 days apart. In some embodiments, doses may be about 14 to about 24 days. In some embodiments, doses may be about 21 to about 42 days.

[001206] In some embodiments, a vaccination regimen comprises a first dose and a second dose. In some embodiments, a first dose and a second dose are administered by at least 21 days apart. In some embodiments, a first dose and a second dose are administered by at least 28 days apart.

[001207] In some embodiments, a vaccination regimen comprises a first dose and a second dose, wherein the amount of RNA administered in the first dose is the same as the amount of RNA administered in the second dose. In some embodiments, a vaccination regimen comprises a first dose and a second dose wherein the amount of RNA administered in the first dose differs from that administered in the second dose.

[001208] In some embodiments, a vaccination regimen comprises a first dose and a second dose, wherein the amount of RNA administered in the first dose is less than that administered in the second dose. In some embodiments, the amount of RNA administered in the first dose is 10%-90% of the second dose. In some embodiments, the amount of RNA administered in the first dose is 10°/o-50% of the second dose. In some embodiments, the amount of RNA administered in the first dose is 10%-20% of the second dose. In some embodiments, the first dose and the second dose are administered at least 2 weeks apart, including, at least 3 weeks apart, at least 4 weeks apart, at least 5 weeks apart, at least 6 weeks apart or longer. In some embodiments, the first dose and the second dose are administered at least 3 weeks apart.

[001209] In some embodiments, a first dose comprises less than about 30 ug of RNA and a second dose comprises at least about 30 ug of RNA. In some embodiments, a first dose comprises about 1 to less than about 30 ug of RNA (e.g., about 0.1, about 1, about 3, about 5, about 10, about 15, about 20, about 25, or less than about 30 ug of RNA) and a second dose comprises about 30 to about 100 ug of RNA (e.g., about 30, about 40, about 50, or about 60 ug of RNA). In some embodiments, a first dose comprises about 1 to about 20 ug of RNA, about 1 to about 10 ug of RNA, or about 1 to about 5 ug of RNA and a second dose comprises about 30 to about 60 ug of RNA.

[001210] In some embodiments, a first dose comprises about 1 to about 10 ug of RNA (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10 ug of RNA) and a second dose comprises about 30 to about 60 ug of RNA (e.g., about 30, about 35, about 40, about 45, about 50, about 55, or about 60 ug of RNA).

[001211] In some embodiments, a first dose comprises about 1 ug of RNA and a second dose comprises about 30 ug of RNA. In some embodiments, a first dose comprises about 3 ug of RNA and a second dose comprises about 30 ug of RNA. In some embodiments, a first dose comprises about 5 ug of RNA and a second dose comprises about 30 ug of RNA. In some embodiments, a first dose comprises about 10 ug of RNA and a second dose comprises about 30 ug of RNA. In some embodiments, a first dose comprises about 15 ug of RNA and a second dose comprises about 30 ug of RNA.

[001212] In some embodiments, a first dose comprises about 1 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 3 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 5 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 6 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 10 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 15 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 20 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 25 ug of RNA and a second dose comprises about 60 ug of RNA. In some embodiments, a first dose comprises about 30 ug of RNA and a second dose comprises about 60 ug of RNA.

[001213] In some embodiments, a first dose comprises less than about 10 ug of RNA and a second dose comprises at least about 10 ug of RNA. In some embodiments, a first dose comprises about 0.1 to less than about 10 ug of RNA (e.g., about 0.1, about 0.5, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, or less than about 10 ug of RNA) and a second dose comprises about 10 to about 30 ug of RNA (e.g., about 10, about 15, about 20, about 25, or about 30 ug of RNA). In some embodiments, a first dose comprises about 0.1 to about 10 ug of RNA, about 1 to about 5 ug of RNA, or about 0.1 to about 3 ug of RNA and a second dose comprises about 10 to about 30 ug of RNA.

[001214] In some embodiments, a first dose comprises about 0.1 to about 5 ug of RNA (e.g., about 0.1, about 0.5, about 1, about 2, about 3, about 4, about 5ug of RNA) and a second dose comprises about 10 to about 20 ug of RNA (e.g., about 10, about 12, about 14, about 16, about 18, about 20ug of RNA).

[001215] In some embodiments, a first dose comprises about 0.1 ug of RNA and a second dose comprises about 10 ug of RNA. In some embodiments, a first dose comprises about 0.3 ug of RNA and a second dose comprises about 10 ug of RNA. In some embodiments, a first dose comprises about 1 ug of RNA and a second dose comprises about 10 ug of RNA. In some embodiments, a first dose comprises about 3 ug of RNA and a second dose comprises about 10 ug of RNA.

[001216] In some embodiments, a first dose comprises less than about 3 ug of RNA and a second dose comprises at least about 3 ug of RNA. In some embodiments, a first dose comprises about 0.1 to less than about 3 ug of RNA (e.g., about 0.1, about 0.2, about 0.3, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.5, about 2.0, or about 2.5 ug of RNA) and a second dose comprises about 3 to about 10 ug of RNA (e.g., about 3, about 4, about 5, about 6, or about 7, about 8, about 9, or about 10 ug of RNA). In some embodiments, a first dose comprises about 0.1 to about 3 ug of RNA, about 0.1 to about 1 ug of RNA, or about 0.1 to about 0.5 ug of RNA and a second dose comprises about 3 to about 10 ug of RNA.

[001217] In some embodiments, a first dose comprises about 0.1 to about 1.0 ug of RNA (e.g., about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1.0 ug of RNA) and a second dose comprises about 1 to about 3 ug of RNA (e.g., about 1.0, about 1.5, about 2.0, about 2.5, or about 3.0 ug of RNA).

[001218] In some embodiments, a first dose comprises about 0.1 ug of RNA and a second dose comprises about 3 ug of RNA. In some embodiments, a first dose comprises about 0.3 ug of RNA and a second dose comprises about 3 ug of RNA. In some embodiments, a first dose comprises about 0.5 ug of RNA and a second dose comprises about 3 ug of RNA. In some embodiments, a first dose comprises about 1 ug of RNA and a second dose comprises about 3 ug of RNA. [001219] In some embodiments, a vaccination regimen comprises a first dose and a second dose, wherein the amount of RNA administered in the first dose is greater than that administered in the second dose. In some embodiments, the amount of RNA administered in the second dose is 10%-90% of the first dose. In some embodiments, the amount of RNA administered in the second dose is 10%-50% of the first dose. In some embodiments, the amount of RNA administered in the second dose is 10%-20% of the first dose. In some embodiments, the first dose and the second dose are administered at least 2 weeks apart, including, at least 3 weeks apart, at least 4 weeks apart, at least 5 weeks apart, at least 6 weeks apart or longer. In some embodiments, the first dose and the second dose are administered at least 3 weeks apart.

[001220] In some embodiments, a first dose comprises at least about 30 ug of RNA and a second dose comprises less than about 30 ug of RNA. In some embodiments, a first dose comprises about 30 to about 100 ug of RNA (e.g., about 30, about 40, about 50, or about 60 ug of RNA) and a second dose comprises about 1 to about 30 ug of RNA (e.g., about 0.1, about 1, about 3, about 5, about 10, about 15, about 20, about 25, or about 30 ug of RNA). In some embodiments, a second dose comprises about 1 to about 20 ug of RNA, about 1 to about 10 ug of RNA, or about 1 to 5 ug of RNA. In some embodiments, a first dose comprises about 30 to about 60 ug of RNA and a second dose comprises about 1 to about 20 ug of RNA, about 1 to about 10 ug of RNA, or about 0.1 to about 3 ug of RNA.

[001221] In some embodiments, a first dose comprises about 30 to about 60 ug of RNA (e.g., about 30, about 35, about 40, about 45, about 50, about 55, or about 60 ug of RNA) and a second dose comprises about 1 to about 10 ug of RNA (e.g., about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10 ug of RNA).

[001222] In some embodiments, a first dose comprises about 30 ug of RNA and a second dose comprises about 1 ug of RNA. In some embodiments, a first dose comprises about 30 ug of RNA and a second dose comprises about 3 ug of RNA. In some embodiments, a first dose comprises about 30 ug of RNA and a second dose comprises about 5 ug of RNA. In some embodiments, a first dose comprises about 30 ug of RNA and a second dose comprises about 10 ug of RNA. In some embodiments, a first dose comprises about 30 ug of RNA and a second dose comprises about 15 ug of RNA.

[001223] In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 1 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 3 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 5 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 6 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 10 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 15 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 20 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 25 ug of RNA. In some embodiments, a first dose comprises about 60 ug of RNA and a second dose comprises about 30 ug of RNA.

[001224] In some embodiments, a first dose comprises at least about 10 ug of RNA and a second dose comprises less than about 10 ug of RNA. In some embodiments, a first dose comprises about 10 to about 30 ug of RNA (e.g., about 10, about 15, about 20, about 25, or about 30 ug of RNA) and a second dose comprises about 0.1 to less than about 10 ug of RNA (e.g., about 0.1, about 0.5, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, or less than about 10 ug of RNA). In some embodiments, a first dose comprises about 10 to about 30 ug of RNA, or about 0.1 to about 3 ug of RNA and a second dose comprises about 1 to about 10 ug of RNA, or about 1 to about 5 ug of RNA. [001225] In some embodiments, a first dose comprises about 10 to about 20 ug of RNA (e.g., about 10, about 12, about 14, about 16, about 18, about 20 ug of RNA) and a second dose comprises about 0.1 to about 5 ug of RNA (e.g., about 0.1, about 0.5, about 1, about 2, about 3, about 4, or about 5 ug of RNA).

[001226] In some embodiments, a first dose comprises about 10 ug of RNA and a second dose comprises about 0.1 ug of RNA. In some embodiments, a first dose comprises about 10 ug of RNA and a second dose comprises about 0.3 ug of RNA. In some embodiments, a first dose comprises about 10 ug of RNA and a second dose comprises about 1 ug of RNA. In some embodiments, a first dose comprises about 10 ug of RNA and a second dose comprises about 3 ug of RNA.

[001227] In some embodiments, a first dose comprises at least about 3 ug of RNA and a second dose comprises less than about 3 ug of RNA. In some embodiments, a first dose comprises about 3 to about 10 ug of RNA (e.g., about 3, about 4, about 5, about 6, or about 7, about 8, about 9, or about 10 ug of RNA) and a second dose comprises 0.1 to less than about 3 ug of RNA (e.g., about 0.1, about 0.2, about 0.3, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.5 about 2.0, or about 2.5 ug of RNA). In some embodiments, a first dose comprises about 3 to about 10 ug of RNA and a second dose comprises about 0.1 to about 3 ug of RNA, about 0.1 to about 1 ug of RNA, or about 0.1 to about 0.5 ug of RNA.

[001228] In some embodiments, a first dose comprises about 1 to about 3 ug of RNA (e.g., about 1, about 1.5, about 2.0, about 2.5, or about 3.0 ug of RNA) and a second dose comprises about 0.1 to 0.3 ug of RNA (e.g., about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1.0 ug of RNA).

[001229] In some embodiments, a first dose comprises about 3 ug of RNA and a second dose comprises about 0.1 ug of RNA. In some embodiments, a first dose comprises about 3 ug of RNA and a second dose comprises about 0.3 ug of RNA. In some embodiments, a first dose comprises about 3 ug of RNA and a second dose comprises about 0.6 ug of RNA. In some embodiments, a first dose comprises about 3 ug of RNA and a second dose comprises about 1 ug of RNA.

[001230] In some embodiments, a vaccination regimen comprises at least two doses, including, e.g., at least three doses, at least four doses or more. In some embodiments, a vaccination regimen comprises three doses. In some embodiments, the time interval between the first dose and the second dose can be the same as the time interval between the second dose and the third dose. In some embodiments, the time interval between the first dose and the second dose can be longer than the time interval between the second dose and the third dose, e.g., by days or weeks (including, e.g., at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, or longer). In some embodiments, the time interval between the first dose and the second dose can be shorter than the time interval between the second dose and the third dose, e.g., by days or weeks (including, e.g., at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, or longer). In some embodiments, the time interval between the first dose and the second dose can be shorter than the time interval between the second dose and the third dose, e.g., by at least 1 month (including, e.g., at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, or longer).

[001231] In some embodiments, a last dose of a primary regimen and a first dose of a booster regimen are given at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, or more apart. In some embodiments, a primary regimen may comprises two doses. In some embodiments, a primary regimen may comprises three doses. [001232] In some embodiments, a first dose and a second dose (and/or other subsequent dose) may be administered by intramuscular injection. In some embodiments, a first dose and a second dose (and/or other subsequent dose) may be administered in the deltoid muscle. In some embodiments, a first dose and a second dose (and/or other subsequent dose) may be administered in the same arm.

[001233] In some embodiments, an RNA (e.g., mRNA) composition described herein is administered (e.g., by intramuscular injection) as a series of two doses (e.g., 0.3 mL each) 21 days apart. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered (e.g., by intramuscular injection) as a series of two doses (e.g., 0.2 mL each) 21 days apart. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered (e.g., by intramuscular injection) as a series of three doses (e.g., 0.3 mL or lower including, e.g., 0.2 mL), wherein doses are given at least 3 weeks apart. In some embodiments, the first and second doses may be administered 3 weeks apart, while the second and third doses may be administered at a longer time interval than that between the first and the second doses, e.g., at least 4 weeks apart or longer (including, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, or longer). In some embodiments, each dose is about 60 ug. In some embodiments, each dose is about 50 ug. In some embodiments, each dose is about 30 ug. In some embodiments, each dose is about 25 ug. In some embodiments, each dose is about 20 ug. In some embodiments, each dose is about 15 ug. In some embodiments, each dose is about 10 ug. In some embodiments, each dose is about 3 ug.

[001234] In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 60 ug. In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 50 ug. In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 30 ug. In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 25 ug. In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 20 ug. In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 15 ug. In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 10 ug. In some embodiments, at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 3 ug. [001235] In one embodiment, an amount of the RNA described herein of about 60 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 50 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 30 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 25 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 20 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 15 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 10 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 5 μg is administered per dose. In one embodiment, an amount of the RNA described herein of about 3 μg is administered per dose. In one embodiment, at least two of such doses are administered. For example, a second dose may be administered about 21 days following administration of the first dose.

[001236] In some embodiments, the efficacy of the RNA vaccine described herein (e.g., administered in two doses, wherein a second dose may be administered about 21 days following administration of the first dose, and administered, for example, in an amount of about 30 μg per dose) is at least 70%, at least 80%, at least 90, or at least 95% beginning 7 days after administration of the second dose (e.g., beginning 28 days after administration of the first dose if a second dose is administered 21 days following administration of the first dose). In some embodiments, such efficacy is observed in populations of age of at least 50, at least 55, at least 60, at least 65, at least 70, or older. In some embodiments, the efficacy of the RNA vaccine described herein (e.g., administered in two doses, wherein a second dose may be administered about 21 days following administration of the first dose, and administered, for example, in an amount of about 30 μg per dose) beginning 7 days after administration of the second dose (e.g., beginning 28 days after administration of the first dose if a second dose is administered 21 days following administration of the first dose) in populations of age of at least 65, such as 65 to 80, 65 to 75, or 65 to 70, is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, or at least 95%. Such efficacy may be observed over time periods of up to 1 month, 2 months, 3 months, 6 months or even longer.

[001237] In one embodiment, vaccine efficacy is defined as the percent reduction in the number of subjects with evidence of infection (vaccinated subjects vs. non-vaccinated subjects).

[001238] In one embodiment, efficacy is assessed through surveillance for potential cases of COVID-19. If, at any time, a patient develops acute respiratory illness, for the purposes herein, the patient can be considered to potentially have COVID-19 illness. The assessments can include a nasal (midturbinate) swab, which may be tested using a reverse transcription-polymerase chain reaction (RT-PCR) test to detect SARS-CoV-2. In addition, clinical information and results from local standard-of-care tests can be assessed.

[001239] In some embodiments, efficacy assessments may utilize a definition of SARS-CoV-2-related cases wherein:

• Confirmed COVID-19: presence of at least 1 of the following symptoms and SARS-CoV-2 NAAT (nucleic acid amplification-based test) positive during, or within 4 days before or after, the symptomatic period: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting.

[001240] Alternatively or additionally, in some embodiments, efficacy assessments may utilize a definition of SARS-CoV-2-related cases wherein one or more of the following additional symptoms defined by the CDC can be considered: fatigue; headache; nasal congestion or runny nose; nausea.

[001241] In some embodiments, efficacy assessments may utilize a definition of SARS-CoV-2-related severe cases

• Confirmed severe COVID-19: confirmed COVID-19 and presence of at least 1 of the following: clinical signs at rest indicative of severe systemic illness (e.g., RR >30 breaths per minute, HR >125 beats per minute, SpO2<93% on room air at sea level, or PaO2/FiO2< 300mm Hg); respiratory failure (which can be defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO); evidence of shock (e.g., SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors); significant acute renal, hepatic, or neurologic dysfunction; admission to an ICU; death.

[001242] Alternatively or additionally, in some embodiments a serological definition can be used for patients without clinical presentation of COVID-19: e.g., confirmed seroconversion to SARS-CoV-2 without confirmed COVID-19: e.g., positive N-binding antibody result in a patient with a prior negative N-binding antibody result. [001243] In some embodiments, any or all of the following assays can be performed on serum samples: SARS-CoV-2 neutralization assay; Sl-binding IgG level assay; RBD-binding IgG level assay; N-binding antibody assay.

[001244] In one embodiment, methods and agents described herein are administered to a paediatric population. In various embodiments, the paediatric population comprises or consists of subjects under 18 years, e.g., 5 to less than 18 years of age, 12 to less than 18 years of age, 16 to less than 18 years of age, 12 to less than 16 years of age, 5 to less than 12 years of age, or 6 months to less than 12 years of age. In various embodiments, the paediatric population comprises or consists of subjects under 5 years, e.g., 2 to less than 5 years of age, 12 to less than 24 months of age, 7 to less than 12 months of age, or less than 6 months of age. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of less than 2 years old, for example, 6 months to less than 2 years old. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of less than 6 months old, for example, 1 month to less than 4 months old. In some embodiments, a dosing regimen (e.g., doses and/or dosing schedule) for a paediatric population may vary for different age groups. For example, in some embodiments, a subject 6 months through 4 years of age may be administered according to a primary regimen comprising at least three doses, in which the initial two doses are administered at least 3 weeks (including, e.g., at least 4 weeks, at least 5 weeks, at least 6 weeks, or longer) apart followed by a third dose administered at least 8 weeks (including, e.g., at least

9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, or longer) after the second dose. In some such embodiments, at least one dose administered is 3 ug RNA described herein. In some embodiments, a subject 5 years of age and older may be administered according to a primary regimen comprising at least two doses, in which the two doses are administered at least 3 weeks (including, e.g., at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, or longer) apart. In some such embodiments, at least one dose administered is

10 ug RNA described herein. In some embodiments, a subject 5 years of age and older who are immunocompromised (e.g., in some embodiments subjects who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent of immunocompromise) may be administered according to a primary regimen comprising at least three doses, in which the initial two doses are administered at least 3 weeks (including, e.g., at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, or longer) apart, followed by a third dose administered at least 4 weeks (including, e.g., at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, or longer) after the second dose.

[001245] In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 12 or older and each dose is about 30 ug. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 12 or older (including, e.g., age 18 or older) and each dose is higher than 30 ug, including, e.g., 35 ug, 40 ug, 45 ug, 50 ug, 55 ug, 60 ug, 65 ug , 70 ug, or higher. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 12 or older and each dose is about 60 ug. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 12 or older and each dose is about 50 ug. In one embodiment, the paediatric population comprises or consists of subjects 12 to less than 18 years of age including subjects 16 to less than 18 years of age and/or subjects 12 to less than 16 years of age. In this embodiment, treatments may comprise 2 vaccinations 21 days apart, wherein, in one embodiment, the vaccine is administered in an amount of 30 μg RNA per dose, e.g., by intramuscular administration. In some embodiments, higher doses are administered to older pediatric patients and adults, e.g., to patients 12 years or older, compared to younger children or infants, e.g. 2 to less than 5 years old, 6 months to less than 2 years old, or less than 6 months old.

In some embodiments, higher doses are administered to children who are 2 to less than 5 years old, as compared to toddlers and/or infants, e.g., who are 6 months to less than 2 years old, or less than 6 months old.

[001246] In one embodiment, the paediatric population comprises or consists of subjects 5 to less than 18 years of age including subjects 12 to less than 18 years of age and/or subjects 5 to less than 12 years of age. In this embodiment, treatments may comprise 2 vaccinations 21 days apart, wherein, in various embodiments, the vaccine is administered in an amount of 10 pg, 20pg, or 30 μg RNA per dose, e.g., by intramuscular administration. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 5 to 11 and each dose is about 10 ug [001247] In some embodiments, each dose comprises about 5 ug of RNA encoding a SARS-CoV-2 S protein of a first variant and about 5 ug of RNA encoding a SARS-CoV-2 S protein of a second variant.

[001248] In one embodiment, the paediatric population comprises or consists of subjects less than 5 years of age including subjects 2 to less than 5 years of age, subjects 12 to less than 24 months of age, subjects 7 to less than 12 months of age, subjects 6 to less than 12 months of age and/or subjects less than 6 months of age. In this embodiment, treatments may comprise 2 vaccinations, e.g., 21 to 42 days apart, e.g., 21 days apart, wherein, in various embodiments, the vaccine is administered in an amount of 3 pg, 6 pg, 10 pg, 20 pg, or 30 pg RNA per dose, e.g., by intramuscular administration. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 2 to less than 5 and each dose is about 3 ug. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of about 6 months to less than about 5 years and each dose is about 3 ug. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 2 to less than 5 and each dose is about 6 ug. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of about 6 months to less than about 5 years and each dose is about 6 ug. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 2 to less than 5 and each dose is about 10 ug. In some such embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of about 6 months to less than about 5 years and each dose is about 10 ug.

[001249] In some embodiments, each dose comprises about 1.5 ug of RNA encoding a SARS-CoV-2 S protein of a first variant and about 1.5 ug of RNA encoding a SARS-CoV-2 S protein of a second variant. In some embodiments, each dose comprises about 1.5 ug of RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and about 1.5 ug of RNA encoding a SARS-CoV-2 S protein of an Omicron variant.

[001250] In some embodiments, each dose comprises about 3 ug of RNA encoding a SARS-CoV-2 S protein of a first variant and about 3 ug of RNA encoding a SARS-CoV-2 S protein of a second variant. In some embodiments, each dose comprises about 3 ug of RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and about 3 ug of RNA encoding a SARS-CoV-2 S protein of an Omicron variant.

[001251] In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 12 or older and at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 60 ug. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 12 or older and at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 30 ug. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 12 or older and at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 15 ug. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 5 to less than 12 years of age and at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 10 ug. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of age 2 to less than 5 and at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 3 ug. In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to subjects of 6 months to less than age 2 and at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 3 ug or lower, including, e.g., 2 ug, 1 ug, or lower). In some embodiments, an RNA (e.g., mRNA) composition described herein is administered to infants of less than 6 months and at least one dose given in a vaccination regimen (e.g., a primary vaccination regimen and/or a booster vaccination regimen) is about 3 ug or lower, including, e.g., 2 ug, 1 ug, 0.5 ug, or lower). [001252] In some embodiments, an RNA (e.g., mRNA) composition described herein is administered (e.g., by intramuscular injection) as a single dose. In some embodiments, a single dose comprise a single RNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof (e.g., an RBD domain, truncated SI domain, or S2 domain). In some embodiments, a single dose comprise at least two RNAs described herein, for example, each RNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof (e.g., an RBD domain) from different strains. In some embodiments, such at least two RNAs described herein can be administered as a single mixture. For example, in some such embodiments, two separate RNA compositions described herein can be mixed to generate a single mixture prior to injection. In some embodiments, such at least two RNAs described herein can be administered as two separate compositions, which, for example, can be administered at different injection sites (e.g., on different arms, or different sites on the same arm).

[001253] In some embodiments, a dose administered to subjects in need thereof may comprise administration of a single RNA (e.g., mRNA) composition described herein.

[001254] In some embodiments, a dose administered to subjects in need thereof may comprise administration of at least two or more (including, e.g., at least three or more) different drug products/formulations. For example, in some embodiments, at least two or more different drug products/formulations may comprise at least two different RNA (e.g., mRNA) compositions described herein (e.g., in some embodiments each comprising a different RNA construct).

[001255] In some embodiments, an RNA (e.g., mRNA) composition disclosed herein may be administered in conjunction with a vaccine targeting a different infectious agent. In some embodiments, the different infectious agent is one that increases the likelihood of a subject experiencing deleterious symptoms when coinfected with SARS-CoV-2 and the infectious agent. In some embodiments, the infectious agent is one that increases the infectivity of SARS-CoV-2 when a subject is coinfected with SARS-CoV-2 and the infectious agent. In some embodiments, at least one RNA (e.g., mRNA) composition described herein may be administered in combination with a vaccine that targets influenza. In some embodiments, at least two or more different drug products/formulations may comprise at least one RNA (e.g., mRNA) composition described herein and a vaccine targeting a different infectious agent (e.g., an influenza vaccine). In some embodiments, different drug products/ formulations are separately administered. In some embodiments, such different drug product/formulations are separately administered at the same time (e.g., at the same vaccination session) at different sites of a subject (e.g., at different arms of the subject).

[001256] In one embodiment, at least two doses are administered. For example, a second dose may be administered about 21 days following administration of the first dose.

[001257] In some embodiments, at least one single dose is administered. In some embodiments, such single dose is administered to subjects, for example, who may have previously received one or more doses of, or a complete regimen of, a SARS-CoV-2 vaccine (e.g., of a BNT162b2 vaccine [including, e.g., as described herein], an mRNA-1273 vaccine, an Ad26.CoV2.S vaccine, a ChAdxOxl vaccine, an NVX-CoV2373 vaccine, a CvnCoV vaccine, a GAM-COVIDOVac vaccine, a CoronaVac vaccine, a BBIBP-CorV vaccine, an Ad5-nCoV vaccine, a zf2001 vaccine, a SCB-2019 vaccine, or other approved RNA (e.g., mRNA) or adenovector vaccines, etc. Alternatively or additionally, in some embodiments, a single dose is administered to subjects who have been exposed to and/or infected by SARS-CoV-2. In some embodiments, at least one single dose is administered to subjects who have received one or more doses of, or a complete regimen of, a SARS-CoV-2 vaccine and have been exposed to and/or infected with SARS-CoV-2.

[001258] In some particular embodiments where at least one single dose is administered to subjects who have received one or more doses of a prior SARS-CoV-2 vaccine, such prior SARS-CoV-2 vaccine is a different vaccine, or a different form (e.g., formulation) and/or dose of a vaccine with the same active (e.g., BNT162b2); in some such embodiments, such subjects have not received a complete regimen of such prior vaccine and/or have experienced one or more undesirable reactions to or effects of one or more received doses of such prior vaccine. In some particular embodiments, such prior vaccine is or comprises higher dose(s) of the same active (e.g., BNT162b2). Alternatively or additionally, in some such embodiments, such subjects were exposed to and/or infected by SARS-CoV-2 prior to completion (but, in some embodiments, after initiation) of a full regimen of such prior vaccine.

[001259] In some embodiments, an RNA described herein is administered to a subject who has previously been administered at least two doses of BNT162b2 (e.g., two doses of BNT162b2 administered about 21 days apart).

[001260] In some embodiment, an RNA described herein is administered to a subject who has previously been administered a vaccine that delivers an antigen of a SARS-CoV-2 variant (e.g., an Omicron BA.4/5 variant (e.g., a vaccine described herein)).

[001261] In one embodiment, at least two doses are administered. For example, a second dose may be administered about 21 days following administration of the first dose.

[001262] In one embodiment, at least three doses are administered. In some embodiments, such third dose is administered a period of time after the second dose that is comparable to (e.g., the same as) the period of time between the first and second doses. For example, in some embodiments, a third dose may be administered about 21 days following administration of the second dose. In some embodiments, a third dose is administered after a longer period of time relative to the second dose than the second dose was relative to the first dose. In some embodiments, a three-dose regimen is administered to an immunocompromised patient, e.g., a cancer patient, an HIV patient, a patient who has received and/or is receiving immunosuppressant therapy (e.g., an organ transplant patient). In some embodiments, the length of time between the second and third dose (e.g., a second and third dose administered to an immunocompromised patient) is at least about 21 days (e.g., at least about 28 days).

[001263] In some embodiments, a vaccination regimen comprises administering the same amount of RNA in different doses (e.g., in first and/or second and/or third and/or subsequent doses). In some embodiments, a vaccination regimen comprises administering different amounts of RNA in different doses. In some embodiments, one or more later doses is larger than one or more earlier doses (e.g., in situations where waning of vaccine efficacy from one or more earlier doses is observed and/or immune escape by a variant (e.g., one described herein) that is prevalent or rapidly spreading is observed in a relevant jurisdiction at the time of administration is observed). In some embodiments, one or more later doses may be larger than one or more earlier doses by at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or higher, provided that safety and/or tolerability of such a dose is clinically acceptable. In some embodiments, one or more later doses may be larger than one or more earlier doses by at least 1.1-fold, at least 1.5-fold, at least 2- fold, at least 3-fold, at least 4-fold, or higher provided that safety and/or tolerability of such a dose is clinically acceptable. In some embodiments, one or more later doses is smaller than one or more earlier doses (e.g., in a negative reaction was experienced after one or more earlier doses and/or if exposure to and/or infection by SARS-CoV-2 between an earlier dose and a subsequent dose). In some embodiments, one or more later doses may be smaller than one or more earlier doses by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or higher. In some embodiments, where different doses are utilized, they are related to one another by identity with and/or dilution of a common stock as described herein.

[001264] In some embodiments, where at least two or more doses are administered (e.g., at least two doses administered in a primary regimen, at least two doses administered in a booster regimen, or at least one dose administered in a primary regimen and at least one dose in a booster regimen), the same RNA compositions described herein may be administered in such doses and each of such doses can be the same or different (as described herein). In some embodiments, where at least two or more doses are administered (e.g., at least two doses administered in a primary regimen, at least two doses administered in a booster regimen, or at least one dose administered in a primary regimen and at least one dose in a booster regimen), different RNA compositions described herein (e.g., different encoded viral polypeptides, e.g., from different coronavirus clades, or from different strains of the same coronavirus clade; different construct elements such as 5' cap, 3' UTR, 5' UTR, etc.; different formulations, e.g., different excipients and/or buffers (e.g., PBS vs. Tris); different LNP compositions; or combinations thereof) may be administered in such doses and each of such doses can be the same or different (e.g., as described herein).

[001265] In some embodiments, a subject is administered two or more RNAs (e.g., as part of either a primary regimen or a booster regimen), wherein the two or more RNAs are administered on the same day or same visit. In some embodiments, the two or more RNAs are administered in separate compositions, e.g., by administering each RNA to a separate part of the subject (e.g., by intramuscular administration to different arms of the subject or to different sites of the same arm of the subject). In some embodiments, the two or more RNAs are mixed prior to administration (e.g., mixed immediately prior to administration, e.g., by the administering practitioner). In some embodiments, the two or more RNAs are formulated together (e.g., by (a) mixing separate populations of LNPs, each population comprising a different RNA; or (b) by mixing two or more RNAs prior to LNP formulation, so that each LNP comprises two or more RNAs). In some embodiments, the two or more RNAs comprise an RNA that encode a coronavirus S protein or immunogenic fragment thereof (e.g., RBD or other relevant domains) from one strain (e.g., Wuhan strain) and a variant that is prevalent or rapidly spreading in a relevant jurisdiction at the time of administration (e.g., a variant described herein). In some embodiments, such a variant is an Omicron variant (e.g., a BA.l, BA.2, or BA.3 variant). In some embodiments, the two or more RNAs comprise a first RNA and a second RNA that have been shown to elicit a broad immune response in subject. In some embodiments the two or more RNAs comprise an RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and an RNA encoding a SARS-CoV-2 S protein from a BA.4 or BA.5 Omicron variant.

[001266] In some embodiments, synergistic categories of coronavirus strain and/or variant sequences (e.g., SARS-CoV-2 strain and/or variant sequences) can be defined, for example, based on shared amino acid alterations in S glycoprotein of coronavirus strain and/or variant sequences. For example, while many of the amino acid changes in the RBD of S protein are shared between Omicron variants (e.g., BA.l, BA.2, BA.2.12.1, and BA.4/5), alterations within the NTD of BA.2 and BA.2-derived sub-lineages including BA.4/5 are mostly distinct from those found in BA.l. Therefore, in some embodiments, synergistic categories of coronavirus strain and/or variant sequences (e.g., SARS-CoV-2 strain and/or variant sequences) can be defined based on the degree of shared amino acid mutations present with the NTD of a S protein. For example, in some embodiments where two SARS-CoV-2 strain and/or variant sequences share at least 50% (including, e.g., at least 60%, at least 70%, at least 80%, at least 90%, or more) of the amino acid mutations present in the NTD of a S protein, both SARS- CoV-2 strain and variant sequences can be grouped into the same category. In some embodiments where two SARS-CoV-2 strain and/or variant sequences share no more 50% (including, e.g., no more than 45%, no more than 40%, no more than 30%, or lower) of the amino acid mutations present in the NTD of a S protein, both SARS-CoV-2 strain and variant sequences can be grouped into different categories. Among other things, the present findings provide insights that exposing subjects (e.g., via infection and/or vaccination) to at least two antigens that are of different synergistic categories (e.g., as shown in the table below) can produce a more robust immune response (e.g., broadening the spectrum of cross-neutralization against different variants and/or producing an immune response that is less prone to immune escape). For example, in some embodiments, vaccine-naive subjects without prior infection may be administered a combination of vaccines, at least two of which are each adapted to a SARS-CoV-2 strain of different synergistic categories. In some embodiments, such vaccines in a combination may be administered at different times, for example, in some embodiments as a first dose and a second dose administered apart by a pre-determined period of time (e.g., according to certain dosing regimens as described herein). In some embodiments, such vaccines in a combination may be administered as a multivalent vaccine. In some embodiments, a subject infected or vaccinated with a SARS-CoV-2 strain of one category may be administered a vaccine adapted to a SARS-CoV-2 strain of a different category (e.g., as described herein). In some embodiments, such a vaccine may be a polypeptide-based or RNA-based vaccine. [001267] In some embodiments, a vaccine can comprise a polypeptide (e.g., a non-natural polypeptide, e.g., a chimeric polypeptide) comprising one or more mutations that are characteristic of one or more different SARS- CoV-2 variants, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide (e.g., a non-natural polypeptide, e.g., a chimeric polypeptide) comprising one or more mutations that are characteristic of a first SARS-CoV-2 variant and one or more mutations that are characteristic of a second SARS-CoV-2 variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide.

[001268] In some embodiments, a composition is administered as a booster dose to a subject previously administered:

(i) a first dose of an RNA vaccine that delivers a SARS-CoV-2 S protein of a Wuhan strain, and a second dose of a bivalent composition comprising a first RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and a second RNA encoding a SARS-CoV-2 S protein of an Omicron BA.4/5 variant, where the bivalent composition was administered about 21 days after the most recent dose of a composition that delivers a SARS-CoV-2 S protein of a Wuhan strain;

(ii) two doses (administered about 21 days apart) of an RNA vaccine that delivers a SARS-CoV-2 S protein of a Wuhan strain, and a dose of a bivalent composition comprising a first RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and a second RNA encoding a SARS-CoV-2 S protein of an Omicron BA.4/5 variant, where the bivalent composition was administered at least about two months after the most recent dose of a composition that delivers a SARS-CoV-2 S protein of a Wuhan strain;

(iii) three doses of an RNA vaccine that delivers a SARS-CoV-2 S protein of a Wuhan strain (where the first and the second dose were administered about 21 days apart and the third dose was administered about 28 days after the second dose) and at least one dose of a bivalent vaccine comprising a first RNA encoding a SARS- CoV-2 S protein of a Wuhan strain and a second RNA encoding a SARS-CoV-2 S protein of an Omicron BA.4/5 variant, where the bivalent composition was administered at least about 2 months after the most recent dose of a composition that delivers a SARS-CoV-2 S protein of a Wuhan strain;

(iv) three doses of an RNA vaccine that delivers a SARS-CoV-2 S protein of a Wuhan strain (where the first and the second dose were administered about 21 days apart and the third dose was administered at least about 2 months after the second dose) and at least one dose of a bivalent vaccine comprising a first RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and a second RNA encoding a SARS-CoV-2 S protein of an Omicron BA.4/5 variant, where the bivalent composition was administered at least about 2 months after the most recent dose of a composition that delivers a SARS-CoV-2 S protein of a Wuhan strain.

(v) four doses of an RNA vaccine that delivers a SARS-CoV-2 S protein of a Wuhan strain (where the first and the second dose are administered about 21 days apart, the third dose was administered about 28 days after the second dose, and the fourth dose was administered at least about 2 months after the third dose) and at least one dose of a bivalent vaccine comprising a first RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and a second RNA encoding a SARS-CoV-2 S protein of an Omicron BA.4/5 variant, where the bivalent composition was administered at least about 2 months after the most recent dose of a composition that delivers a SARS-CoV-2 S protein of a Wuhan strain; or four doses of an RNA vaccine that delivers a SARS-CoV-2 S protein of a Wuhan strain (where the first and the second dose were administered about 21 days apart, the third dose was administered at least about 2 months after the second dose, and the fourth dose was administered at least about 4 months after the third dose) and at least one dose of a bivalent vaccine comprising a first RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and a second RNA encoding a SARS-CoV-2 S protein of an Omicron BA.4/5 variant, where the bivalent composition was administered at least about 2 months after the most recent dose of a composition that delivers a SARS-CoV-2 S protein of a Wuhan strain

[001269] In some embodiments, a composition described herein is administered to a subject previously administered a dosing regimen as summarized in the below Table E.

Table E: Exemplary Dosing Regimens comprising 3 doses

[001270] In some embodiments, a composition described herein is administered to a subject previously administered a dosing regimen as summarized in the below Table F.

Table F: Exemplary Dosing Regimens comprising 4 doses

[001271] In some embodiments, a composition described herein is administered to a vaccine naive subject and/or a subject who has not previously received a vaccine. In some embodiments, a first dose and a second dose listed in Table E or F are administered about 21 days apart. In some embodiments, a third dose listed in Table E or F is administered at least about 2 months after a second dose. In some embodiments, a fourth dose listed in Table F is administered at least about two months after a third dose.

[001272] In some embodiments, a vaccine can comprise a polypeptide that comprises an RBD comprising one or more mutations characteristic of a BA.l Omicron variant and an NTD comprising one or more mutations characteristic of a second SARS-CoV-2 variant that is not a BA.l Omicron variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise or encode a polypeptide comprising an NTD comprising one or more mutations characteristic of a BA.l Omicron variant and an RBD comprising one or more mutations characteristic of a second SARS-CoV-2 variant that is not a BA.l Omicron variant. In some embodiments, a vaccine can comprise a polypeptide that comprises an RBD comprising one or more mutations characteristic of a BA.l Omicron variant and an NTD comprising one or more mutations characteristic of a BA.2 Omicron variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises an RBD comprising one or more mutations characteristic of a BA.l Omicron variant and an NTD comprising one or more mutations characteristic of a BA.4/5 Omicron variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide.

[001273] In some embodiments, a vaccine can comprise a polypeptide that comprises an NTD comprising one or more mutations characteristic of a BA.l Omicron variant and an RBD comprising one or more mutations characteristic of a second SARS-CoV-2 variant that is not a BA.l Omicron variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises an RBD comprising one or more mutations characteristic of a BA.l Omicron variant and an NTD comprising one or more mutations characteristic of a second SARS-CoV-2 variant that is not a BA.l Omicron variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises an NTD comprising one or more mutations characteristic of a BA.l Omicron variant and an RBD comprising one or more mutations characteristic of a BA.2 Omicron variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises one or more mutations characteristic of an NTD of a BA.l Omicron variant and an RBD comprising one or more mutations characteristic of a BA.4/5 Omicron variant, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide.

[001274] In some embodiments, a vaccine can comprise a polypeptide that comprises an RBD comprising one or more mutations characteristic of a BA.l Omicron variant and an NTD of a Wuhan S protein, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises an RBD comprising one or more mutations characteristic of a BA.2 Omicron variant and an NTD of a Wuhan S protein, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises an RBD comprising one or more mutations characteristic of a BA.4/5 Omicron variant and an NTD of a Wuhan S protein, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide.

[001275] In some embodiments, a vaccine can comprise a polypeptide that comprises an NTD comprising one or more mutations characteristic of a BA.l Omicron variant and an RBD of a Wuhan S protein, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises an NTD comprising one or more mutations characteristic of a BA.2 Omicron variant and an RBD of a Wuhan S protein, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide. In some embodiments, a vaccine can comprise a polypeptide that comprises an NTD comprising one or more mutations characteristic of a BA.4/5 Omicron variant and an RBD of a Wuhan S protein, or a nucleic acid (e.g., in some embodiments an RNA) encoding the polypeptide.

[001276] In some embodiments, a subject is administered a first RNA and a second RNA, each in the same amount (i.e., at a 1:1 ratio).

[001277] In some embodiments, a subject is administered a first RNA and a second RNA, each in a different amount. For example, in some embodiments, a subject is administered a first RNA in an amount that is 0.01 to 100 times that of a second RNA (e.g., wherein the amount of a first RNA is 0.01 to 50, 0.01 to 4, 0.01 to 30, 0.01 to 25, 0.01 to 20, 0.01 to 15, 0.01 to 10, 0.01 to 9, 0.01 to 8, 0.01 to 7, 0.01 to 6, 0.01 to 5, 0.01 to 4, 0.01 to 3, 0.01 to 2, 0.01 to 1.5, 1 to 50, 1 to 4, 1 to 30, 1 to 25, 1 to 20, 1 to 15, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 to 1.5 times that of a second RNA). In some embodiments, a subject is administered a first RNA and a second RNA, wherein the concentration of the first RNA is 1 to 10 times that of the second RNA. In some embodiments, a subject is administered a first RNA and a second RNA, wherein the amount of the first RNA is 1 to 5 times that of the second RNA. In some embodiments, a subject is administered a first RNA and a second RNA, wherein the concentration of the first RNA is 1 to 3 times that of the second RNA. In some embodiments, a subject is administered a first RNA and a second RNA, wherein the amount of the first RNA is 2 times that of the second RNA. In some embodiments, a subject is administered a first RNA and a second RNA, wherein the concentration of the first RNA is 3 times that of the second RNA.

[001278] In some embodiments, a subject is administered three RNAs, each encoding a SARS-CoV-2 S protein comprising one or more mutations characteristic of a different SARS-CoV-2 variant, and each in the same amount (i.e., at a 1:1:1 ratio).

[001279] In some embodiments, a subject is administered three RNAs, each encoding a SARS-CoV-2 S protein comprising one or more mutations characteristic of a different SARS-CoV-2 variant, wherein the amount of each RNA is not the same (e.g., one RNA is present in an amount that is different than the other two RNA, or all three RNAs are present in different amounts). For example, in some embodiments, the ratio of first RNA:second RNA:third RNA is 1: 0.01-100: 0.01-100 (e.g., 1: 0.01-50: 0.01-50; 1: 0.01-40: 0.01-40; 1: 0.01-30: 0.01-25; 1: 0.01-25: 0.01-25; 1: 0.01-20: 0.01-20; 1: 0.01-15: 0.01-15; 1: 0.01-10: 0.01-9; 1: 0.01-9: 0.01-9; 1: 0.01-8: 0.01-8; 1: 0.01-7: 0.01-7; 1: 0.01-6: 0.01-6; 1: 0.01-5: 0.01-5; 1: 0.01-4: 0.01-4; 1: 0.01-3: 0.01-3; 1: 0.01-2: 0.01-2; or 1: 0.01-1.5: 0.01-1.5). In some embodiments, a subject is administered three RNAs at a ratio of 1:1:3. In some embodiments, a subject is administered three RNAs at a ratio of 1:3:3.

[001280] In some embodiments, a vaccination regimen comprises a first vaccination regimen (e.g., a primary regimen) that includes at least two doses of an RNA composition as described herein, e.g., wherein the second dose may be administered about 21 days following administration of the first dose, and a second vaccination (e.g., a booster regimen) that comprises a single dose or multiple doses, e.g., two doses, of an RNA composition as described herein. In some embodiments, doses of a booster regimen are related to those of a primary regimen by identity with or dilution from a common stock as described herein. In various embodiments, a booster regimen is administered (e.g., is initiated) at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, or at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, or longer, after administration of a primary regimen, e.g., after completion of a primary regimen comprising at least two doses. In various embodiments, a booster regimen is administered (e.g., is initiated) 1-12 months, 2-12 months, 3-12 months, 4-12 months, 6-12 months, 1-6 months, 1-5 months, 1-4 months, 1-3 months, or 2-3 months after administration of a primary regimen, e.g., after completion of a primary regimen comprising at least two doses. In various embodiments, a booster regimen is administered (e.g., is initiated) 1 to 60 months, 2 to 48 months, 2 to 24 months, 3 to 24 months, 6 to 18 months, 6 to 12 months, or 5 to 7 months after administration of a primary regimen, e.g., after completion of a two-dose primary regimen. In some embodiments, each dose of a primary regimen is about 60 μg per dose. In some embodiments, each dose of a primary regimen is about 50 pg per dose. In some embodiments, each dose of a primary regimen is about 30 μg per dose. In some embodiments, each dose of a primary regimen is about 25 μg per dose. In some embodiments, each dose of a primary regimen is about 20 μg per dose. In some embodiments, each dose of a primary regimen is about 15 pg per dose. In some embodiments, each dose of a primary regimen is about 10 μg per dose. In some embodiments, each dose of a primary regimen is about 3 μg per dose. In some embodiments, each dose of a booster regimen is the same as that of the primary regimen. In some embodiments, each dose of a booster regimen comprises the same amount of RNA as a dose administered in a primary regimen. In some embodiments, at least one dose of a booster regimen is the same as that of the primary regimen. In some embodiments, at least one dose of a booster regimen comprises the same amount of RNA as at least one dose of a primary regimen. In some embodiments, at least one dose of a booster regimen is lower than that of the primary regimen. In some embodiments, at least one dose of a booster regimen comprises an amount of RNA that is lower than that of a primary regimen. In some embodiments, at least one dose of a booster regimen is higher than that of the primary regimen. In some embodiments, at least one dose of a booster regimen comprises an amount of RNA that is higher than that of a primary regimen.

[001281] In some embodiments, a booster regimen (e.g., as described herein) is administered to a pediatric patient (e.g., a patient aged 2 through 5 years old, a patient aged 5 through 11 years old, or a patient aged 12 through 15 years old). In some embodiments, a booster regimen is administered to a pediatric patient who is 6 months old to less than 2 years old. In some embodiments, a booster regimen is administered to a pediatric patient who is less than 6 months old. In some embodiments, a booster regimen is administered to a pediatric patient who is 6 months old to less than 5 years old. In some embodiments, a booster regimen is administered to a pediatric patient who is 2 years old to less than 5 years old. In some embodiments, a booster regimen is administered to a pediatric patient who is 5 years old to less than 12 years old. In some embodiments, a booster regimen is administered to a pediatric patient who is 12 years old to less than 16 years old. In some embodiments, each dose of a pediatric booster regimen comprises about 3 μg of RNA. In some embodiments, each dose of a pediatric booster regimen comprises about 10 μg of RNA. In some embodiments, each dose of a pediatric booster regimen comprises about 15 μg of RNA. In some embodiments, each dose of a pediatric booster regimen comprises about 20 μg of RNA. In some embodiments, each dose of a pediatric booster regimen comprises about 25 μg of RNA. In some embodiments, each dose of a pediatric booster regimen comprises about 30 μg of RNA. In some embodiments, a booster regimen is administered to a non-pediatric patient (e.g., a patient 16 years or older, a patient aged 18 through 64 years old, and/or a patient 65 years and older). In some embodiments, each dose of a non-pediatric booster regimen comprises about 3 ug of RNA, about 10 ug of RNA, about 25 μg or RNA, about 30 μg of RNA, about 40 μg of RNA, about 45 μg of RNA, about 50 μg of RNA, about 55 μg of RNA, or about 60 μg of RNA . In some embodiments, the same booster regimen may be administered to both pediatric and non-pediatric patients (e.g., to a patient 12 years or older). In some embodiments, a booster regimen that is administered to a non-pediatric patient is administered in a formulation and dose that is related to that of a primary regimen previously received by the patient by identity with or by dilution as described herein. In some embodiments, a non-pediatric patient who receives a booster regimen at a lower dose than a primary regimen may have experienced an adverse reaction to one or more doses of such primary regimen and/or may have been exposed to and/or infected by SARS-CoV-2 between such primary regimen and such booster regimen, or between doses of such primary regimen and/or of such booster regimen. In some embodiments, pediatric and non-pediatric patients may receive a booster regimen at a higher dose than a primary regimen when waning of vaccine efficacy at lower doses is observed, and/or when immune escape of a variant that is prevalent and/or spreading rapidly at a relevant jurisdiction at the time of administration is observed. [001282] In some embodiments one or more doses of a booster regimen differs from that of a primary regimen. For example, in some embodiments, an administered dose may correspond to a subject's age and a patient may age out of one treatment age group and into a next. Alternatively or additionally, in some embodiments, an administered dose may correspond to a patient's condition (e.g., immunocompromised state) and a different dose may be selected for one or more doses of a booster regimen than for a primary regimen (e.g., due to intervening cancer treatment, infection with HIV, receipt of immunosuppressive therapy, for example associated with an organ transplant. In some embodiments, at least one dose of a booster regimen may comprise an amount of RNA that is higher than at least one dose administered in a primary regimen (e.g., in situations where waning of vaccine efficacy from one or more earlier doses is observed and/or immune escape by a variant (e.g., one described herein) that is prevalent or rapidly spreading is observed in a relevant jurisdiction at the time of administration).

[001283] In some embodiments, a primary regimen may involve one or more 3 ug doses and a booster regimen may involve one or more 10 ug doses, and/or one or more 20 ug doses, or one or more 30 ug doses. In some embodiments, a primary regimen may involve one or more 3 ug doses and a booster regimen may involve one or more 3 ug doses. In some embodiments, a primary regimen may involve two or more 3 ug doses (e.g., at least two doses, each comprising 3 ug of RNA, and administered about 21 days after one another) and a booster regimen may involve one or more 3 ug doses. In some embodiments, a primary regimen may involve one or more 10 ug doses and a booster regimen may involve one or more 20 ug doses, and/or one or more 30 ug doses. In some embodiments, a primary regimen may involve one or more 10 ug doses and a booster regimen may involve one or more 10 ug doses. In some embodiments, a primary regimen may involve two or more 10 ug doses (e.g., two doses, each comprising 10 ug of RNA, administered about 21 days apart) and a booster regimen may involve one or more 10 ug doses. In some embodiments, a primary regimen may involve one or more 20 ug doses and a booster regimen may involve one or more 30 ug doses. In some embodiments, a primary regimen may involve one or more 20 ug doses and a booster regimen may involve one or more 20 ug doses. In some embodiments, a primary regimen may involve one or more 30 ug doses, and a booster regimen may also involve one or more 30 ug doses. In some embodiments, a primary regimen may involve two or more 30 ug doses (e.g., two doses, each comprising 30 ug of RNA, administered about 21 days apart), and a booster regimen may also involve one or more 30 ug doses. In some embodiments, a primary regimen may involve two or more 30 ug doses (e.g., two doses, each comprising 30 ug of RNA, administered about 21 days apart), and a booster regimen may involve one or more 50 ug doses. In some embodiments, a primary regimen may involve two or more 30 ug doses (e.g., two doses, each comprising 30 ug of RNA, administered about 21 days apart), and a booster regimen may involve one or more 60 ug doses.

[001284] In some embodiments, a subject is administered a booster regimen comprising at least one 30 ug dose of RNA. In some embodiments, a subject is administered a booster regimen comprising at least one 30 ug dose of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain of SARS-CoV-2 (e.g., BNT162b2). In some embodiments, a subject is administered a booster regimen comprising at least one dose of 30 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of a SARS-CoV-2 variant (e.g., a variant described herein). In some embodiments, a subject is administered a booster regimen comprising at least one dose of 30 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant (e.g., a BA.l, BA.2, BA.3, or BA.4 or BA.5 Omicron variant). In some embodiments, a subject is administered a booster regimen comprising at least one dose of 30 ug of RNA, wherein the 30 ug of RNA comprises RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and RNA encoding a SARS-CoV-2 S protein comprising mutations that are characteristic of a SARS-CoV-2 variant (e.g., in some embodiments, a subject is administered a booster regimen comprising at least one dose comprising 15 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 15 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant). In some embodiments, a subject is administered a booster regimen comprising at least one dose comprising 15 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 15 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of a BA.4 or BA.5 Omicron variant. In some embodiments, a subject is administered a booster regimen comprising at least one dose comprising 10 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 20 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of a BA.4 or BA.5 Omicron variant. In some embodiments, a subject is administered a booster regimen comprising at least one dose comprising 7.5 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 22.5 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of a BA.4 or BA.5 Omicron variant.

[001285] In some embodiments, a subject is administered a booster regimen comprising two or more doses of 30 ug of RNA, administered at least two months apart from each other. For example, in some embodiments, subjects are administered a booster regimen comprising two doses of 30 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant (e.g., a BA.l, BA.2, or BA.4 or BA.5 Omicron variant).

[001286] In some embodiments, a subject is administered (i) a primary regimen comprising at least two 30 ug doses of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein the two doses are administered at least approximately 21 days apart, and (ii) a booster regimen comprising a dose of 30 ug of RNA encoding a SARS-CoV-2 S protein having one or mutations that are characteristic of an Omicron variant of SARS-CoV-2 (e.g., a BA.l, BA.2, BA.3, BA.4, or BA.5 Omicron variant), wherein the booster regimen is administered at least two months (including, e.g., at least three months, at least four months, at least five months, at least six months, or more) after completion of the primary regimen. In some embodiments, a subject is administered (i) a primary regimen comprising at least two 30 ug doses of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein the two doses are administered at least approximately 21 days apart, and (ii) a booster regimen comprising a 30 ug dose of RNA comprising 15 ug RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 15 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant.

[001287] In some embodiments, a subject is administered (i) a primary regimen comprising two 30 ug doses of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein the two doses are administered at least approximately 21 days apart, and (ii) a booster regimen comprising at least two 30 ug doses of RNA encoding a SARS-CoV-2 S protein having one or more mutations characteristic of an Omicron variant, wherein the booster regimen is administered at least two months (including, e.g., at least three months, at least four months, at least five months, at least six months, or more) after completion of the primary regimen, and the two booster doses are administered at least two months apart from each other.

[001288] In some embodiments, a subject is administered a booster regimen comprising at least one 50 ug dose of RNA. In some embodiments, a subject is administered a booster regimen comprising at least one dose of 50 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of a SARS- CoV-2 variant (e.g., a variant described herein). In some embodiments, a subject is administered a booster regimen comprising at least one dose of 50 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant. In some embodiments, a subject is administered a booster regimen comprising at least one 50 ug dose of RNA, wherein the 50 ug of RNA comprises RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and RNA encoding a SARS-CoV-2 S protein comprising mutations that are characteristic of a SARS-CoV-2 variant (e.g., in some embodiments, a subject is administered a booster regimen comprising a 50 ug dose of RNA comprising 25 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 25 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant).

[001289] In some embodiments, a subject is administered (i) a primary regimen comprising two 30 ug doses of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein the two doses are administered approximately 21 days apart, and (ii) a booster regimen comprising at least one 50 ug dose of RNA encoding a SARS-CoV-2 S protein having one or mutations that are characteristic of an Omicron variant of SARS-CoV-2 (e.g., a BA.l, BA.2, BA.4 or BA.5 Omicron variant), wherein the booster regimen is administered at least two months (including, e.g., at least three months, at least four months, at least five months, at least six months, or more) after completion of the primary regimen. In some embodiments, a subject is administered (i) a primary regimen comprising two 30 ug doses of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein the two doses are administered approximately 21 days apart, and (ii) a booster regimen comprising at least one 50 ug dose of RNA, wherein the 50 ug of RNA comprises 25 ug of RNA encoding a SARS-CoV-2 S protein of a Wuhan strain and 25 ug of RNA encoding a SARS-CoV-2 S protein having one or mutations that are characteristic of an Omicron variant (e.g., a BA.l, BA.2, BA.4, or BA.5 variant), wherein the booster regimen is administered at least two months (including, e.g., at least three months, at least four months, at least five months, at least six months, or more) after completion of a first booster regimen.

[001290] In some embodiments, a subject is administered a booster regimen comprising at least one 60 ug dose of RNA. In some embodiments, a subject is administered 60 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of a SARS-CoV-2 variant (e.g., a variant described herein). In some embodiments, a subject is administered a booster regimen comprising 60 ug of RNA encoding a SARS- CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant (e.g., an XBB.1.5, XBB.1.16, XBB.2.3, or XBB.2.3.2 Omicron variant). In some embodiments, a subject is administered a booster regimen comprising 60 ug of RNA, wherein the RNA comprises a first RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, and at least one additional RNA encoding a SARS-CoV-2 S protein comprising mutations that are characteristic of a SARS-CoV-2 variant (e.g., in some embodiments, a subject is administered a booster regimen comprising 30 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 30 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant (e.g., an XBB.1.5, XBB.1.16, XBB.2.3, or XBB.2.3.2 variant).

[001291] In some embodiments, a subject is administered (i) a primary regimen comprising two 30 ug doses of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein the two doses are administered approximately 21 days apart, and (ii) a booster regimen comprising at least one 60 ug dose of RNA encoding a SARS-CoV-2 S protein having one or mutations that are characteristic of an Omicron variant of SARS-CoV-2 (e.g., an XBB.1.5, XBB.1.16, XBB.2.3, or XBB.2.3.2 Omicron variant), wherein the booster regimen is administered at least two months (including, e.g., at least three months, at least four months, at least five months, at least six months, or more) after completion of the primary regimen. In some embodiments, a subject is administered (i) a primary regimen comprising two 30 ug doses of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein the two doses are administered approximately 21 days apart, and (iii) a booster regimen comprising at least one 60 ug dose of RNA comprising 30 ug of RNA encoding a SARS-CoV-2 S protein having one or mutations that are characteristic of an Omicron variant of SARS-CoV-2 and 30 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, wherein a second booster regimen is administered at least two months (including, e.g., at least three months, at least four months, at least five months, at least six months, or more) after completion of a first booster regimen.

[001292] In some embodiments, a patient is administered a primary regimen comprising two 30 ug doses, administered approximately 21 days apart, and a booster regimen comprising at least one 60 ug dose of RNA (e.g., 60 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, 60 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant (e.g., an XBB.1.5, XBB.1.16, XBB.2.3, or XBB.2.3.2 Omicron variant), or 30 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 30 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant). In some embodiments, a patient is administered a primary regimen comprising two 30 ug doses, administered approximately 21 days apart, and a booster regimen comprising at least one 50 ug dose of RNA (e.g., 50 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, 50 ug of RNA encoding a SARS- CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant, or 25 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 25 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant). In some embodiments, a patient is administered a primary regimen comprising two 30 ug doses, administered approximately 21 days apart, and a booster regimen comprising at least one 30 ug dose of RNA (e.g., 30 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain, 30 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant, or 15 ug of RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and 15 ug of RNA encoding a SARS-CoV-2 S protein having one or more mutations that are characteristic of an Omicron variant).

[001293] In some embodiments, a primary regimen may involve one or more 30 ug doses and a booster regimen may involve one or more 20 ug doses, one or more 10 ug doses, and/or one or more 3 ug doses. In some embodiments, a primary regimen may involve one or more 20 ug doses and a booster regimen may involve one or more 10 ug doses, and/or one or more 3 ug doses. In some embodiments, a primary regimen may involve one or more 10 ug doses and a booster regimen may involve one or more 3 ug doses. In some embodiments, a primary regimen may involve one or more 3 ug doses, and a booster regimen may also involve one or more 3 ug doses.

[001294] In some embodiments, a booster regimen comprises a single dose, e.g., for patients who experienced an adverse reaction while receiving the primary regimen.

[001295] In some embodiments, the same RNA as used in a primary regimen is used in a booster regimen. In some embodiment, an RNA used in primary and booster regimens is BNT162b2.

[001296] In some embodiments, a different RNA is used in a booster regimen relative to that used in a primary regimen administered to the same subject. In some embodiments, BNT162b2 is used in a primary regimen but not in a booster regimen. In some embodiments, BNT162b2 is used in a booster regimen but not in a primary regimen. In some embodiments, a similar BNT162b2 construct can be used in a primary regimen and in a booster regimen, except that the RNA constructs used in the primary and booster regimens encode a SARS- CoV-2 S protein (or an immunogenic portion thereof) of different SARS-CoV-2 strains (e.g., as described herein). [001297] In some embodiments, where BNT162b2 is used for a primary regimen or a booster regimen but not both, and a different RNA is used in the other, such different RNA may be an RNA encoding the same SARS- CoV-2 S protein but with different codon optimization or other different RNA sequence. In some embodiments, such different RNA may encode a SARS-CoV-2 S protein (or an immunogenic portion thereof) of a different SARS- CoV-2 strain, e.g., of a variant strain discussed herein. In some such embodiments, such variant strain that is prevalent or rapidly spreading in a relevant jurisdiction. In some embodiments, such different RNA may be an RNA encoding a SARS-CoV-2 S protein or variant thereof (or immunogenic portion of either) comprising one or more mutations described herein for S protein variants such as SARS-CoV-2 S protein variants, in particular naturally occurring S protein variants; in some such embodiments, a SARS-CoV-2 variant may be selected from the group consisting of VOC-202012/01, 501. V2, Cluster 5 and B.1.1.248. In some embodiments, a SARS-CoV-2 variant may be selected from the group consisting of VOC-202012/01, 501. V2, Cluster 5 and B.l.1.248, B.l.1.7, B.1.617.2, and B.l.1.529. In some embodiments, a booster regimen comprises at least one dose of RNA that encodes a SARS-CoV-2 S protein (or an immunogenic fragment thereof) of a variant that is spreading rapidly in a relevant jurisdiction at the time of administration. In some such embodiments, a variant that is encoded by RNA administered in a booster regimen may be different from that encoded by RNA administered in a primary regimen.

[001298] In some embodiments, a booster regimen comprises administering (i) a dose of RNA encoding the same SARS-CoV-2 S protein (or an immunogenic fragment thereof) as the RNA administered in the primary regimen (e.g., an RNA encoding a SARS-CoV-2the S protein (or an immunogenic fragment thereof) from the SARS-CoV-2 Wuhan strain) and (ii) a dose of RNA encoding a SARS-CoV-2 S protein (or an immunogenic fragment thereof) of a variant that is spreading rapidly in a relevant jurisdiction at the time of administration (e.g., a SARS-CoV-2 S protein (or an immunogenic fragment thereof) from one of the SARS-CoV-2 variants discussed herein).

[001299] In some embodiments, a booster regimen comprises multiple doses (e.g., at least two doses, at least three doses, or more). For example, in some embodiments, a first dose of a booster regimen may comprise an RNA encoding the same SARS-CoV-2 S protein (or an immunogenic fragment thereof) administered in the primary regimen and a second dose of a booster regimen may comprise the RNA encoding a SARS-CoV-2 S protein of a variant that is spreading rapidly in a relevant jurisdiction at the time of administration. In some embodiments, a first dose of a booster regimen may comprise RNA encoding a SARS-CoV-2 S protein (or an immunogenic fragment thereof) of a variant that is spreading rapidly in a relevant jurisdiction at the time of administration and a second dose of a booster regimen may comprise RNA encoding the same SARS-CoV-2 S protein (or an immunogenic fragment thereof) administered in the primary regimen. In some embodiments, the booster regimen comprises multiple doses, and the RNA encoding the S protein of a variant that is spreading rapidly in a relevant jurisdiction is administered in a first dose and the RNA encoding the S protein administered in the primary regimen is administered in a second dose.

[001300] In some embodiments, doses (e.g., a first and a second dose or any two consecutive doses) in a booster regimen are administered at least 2 weeks apart, including, e.g., at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 week, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, at least 15 weeks, at least 16 weeks, or longer, apart. In some embodiments, doses (e.g., a first and a second dose or any two consecutive doses) in a booster regimen are administered approximately 2 to 168 weeks apart. In some embodiments, doses (e.g., a first and a second dose or any two consecutive doses) in a booster regimen are administered approximately 3 to 12 weeks apart. In some embodiments, doses (e.g., a first and a second dose or any two consecutive doses) in a booster regimen are administered approximately 4 to 10 weeks apart. In some embodiments, doses (e.g., a first and a second dose or any two consecutive doses) in a booster regimen are administered approximately 6 to 8 weeks apart, (e.g., about 21 days apart, or about 6 to 8 weeks apart). In some embodiments, the first and second dose are administered on the same day (e.g., by intramuscular injection at different sites on the subject).

[001301] In such embodiments, the booster regimen can optionally further comprise a third and fourth dose, administered approximately 2 to 8 weeks after the first and second dose (e.g., about 21 days after the first and second dose, or about 6 weeks to about 8 weeks after the first and second dose), where the third and fourth dose are also administered on the same day (e.g., by intramuscular injection at different sites on the subject), and comprise the same RNAs administered in the first and second doses of the booster regimen.

[001302] In some embodiments, multiple booster regimens may be administered. In some embodiments, a booster regimen is administered to a patient who has previously been administered a booster regimen.

[001303] In some embodiments, a second booster regimen is administered to a patient who has previously received a first booster regimen, and the amount of RNA administered in at least one dose of a second booster regimen is higher than the amount of RNA administered in at least one dose of a first booster regimen.

[001304] In some embodiments, a second booster regimen comprises administering at least one dose of 3 ug of RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 5 ug of RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 10 ug of

RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 15 ug of

RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 20 ug of

RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 25 ug of

RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 30 ug of

RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 50 ug of

RNA. In some embodiments, a second booster regimen comprises administering at least one dose of 60 ug of

RNA.

[001305] In some embodiments, a subject is administered a primary regimen that comprises two doses of 30 ug of RNA, administered approximately 21 days apart, and a booster regimen comprising at least one dose of approximately 30 ug of RNA. In some embodiments, a subject is administered a primary regimen that comprises two doses of 30 ug of RNA, administered approximately 21 days apart, and a booster regimen comprising at least one dose of approximately 50 ug of RNA. In some embodiments, a subject is administered a primary regimen that comprises two doses of 30 ug of RNA, administered approximately 21 days apart, and a booster regimen comprising at least one dose of approximately 60 ug of RNA.

[001306] In some embodiments, a subject is administered a primary regimen that comprises two doses of 30 ug of RNA, administered approximately 21 days apart, a first booster regimen comprising at least one dose of approximately 30 ug of RNA, and a second booster regimen comprising at least one dose of approximately 30 ug of RNA. In some embodiments, a subject is administered a primary regimen that comprises two doses of 30 ug of RNA, administered approximately 21 days apart, a first booster regimen comprising at least one dose of approximately 30 ug of RNA, and a second booster regimen comprising at least one dose of approximately 50 ug of RNA. In some embodiments, a subject is administered a primary regimen that comprises two doses of 30 ug of RNA, administered approximately 21 days apart, a first booster regimen comprising at least one dose of approximately 30 ug of RNA, and a second booster regimen comprising at least one dose of approximately 60 ug of RNA. In some embodiments, a first booster regimen comprises two doses of RNA, wherein each dose comprises an RNA encoding a Spike protein from a different SARS-CoV-2 variant. In some embodiments, a first booster regimen comprises two doses of RNA, wherein each dose comprises an RNA encoding a Spike protein from a different SARS-CoV-2 variant, and wherein the two doses of RNA are administered on the same day. In some embodiments, the two doses of RNA are administered in a single composition (e.g., by mixing a first composition comprising an RNA encoding a Spike protein from a first SARS-CoV-2 variant with a second composition comprising an RNA encoding a Spike protein from a second SARS-CoV-2 variant).

[001307] In some embodiments, a subject is administered a booster regimen comprising a first dose comprising an RNA that encodes a Spike protein from a Wuhan strain of SARS-CoV-2 and a second dose comprising an RNA that encodes a Spike protein comprising mutations from a variant that is prevalent and/or rapidly spreading in a relevant jurisdiction at the time of administering the booster regimen, wherein the first dose and the second dose of RNA may be administered on the same day. In some embodiments, a subject is administered a booster regimen comprising a first dose comprising an RNA that encodes a Spike protein from a Wuhan strain of SARS-CoV-2 and a second dose comprising an RNA that encodes a Spike protein comprising mutations from an alpha variant of SARS-CoV-2, wherein the first dose and the second dose may be administered on the same day. In some embodiments, a subject is administered a booster regimen comprising a first dose comprising an RNA that encodes a Spike protein from a Wuhan strain of SARS-CoV-2 and a second dose comprising an RNA that encodes a Spike protein comprising mutations from a beta variant of SARS-CoV-2, wherein the first dose and the second dose may be administered on the same day. In some embodiments, a subject is administered a booster regimen comprising a first dose comprising an RNA that encodes a Spike protein from a Wuhan strain of SARS-CoV-2 and a second dose comprising an RNA that encodes a Spike protein comprising mutations from a delta variant of SARS-CoV-2, wherein the first dose and the second dose may be administered on the same day. In some embodiments, a subject is administered a booster regimen comprising a first dose comprising an RNA that encodes a Spike protein from a Wuhan strain of SARS-CoV-2 and a second dose comprising an RNA that encodes a Spike protein comprising mutations from an Omicron variant of SARS-CoV-2, wherein the first dose and the second dose may be administered on the same day. Such booster regimens may be administered, e.g., to a subject previously administered a primary dosing regimen and/or to a subject previously administered a primary dosing regimen and a booster regimen.

[001308] In some embodiments, a subject is administered a first booster regimen comprising a first dose of 15 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 15 ug of RNA encoding a Spike protein from an Omicron variant of SARS-CoV-2, where the first and the second dose are administered on the same day (e.g., wherein compositions comprising the RNA are mixed prior to administration, and the mixture is then administered to a patient). In some embodiments, a subject is administered a first booster regimen comprising a first dose of 25 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 25 ug of RNA encoding a Spike protein from an Omicron variant of SARS-CoV-2. In some embodiments, the first and the second doses are optionally administered on the same day. In some embodiments, a subject is administered a first booster regimen comprising a first dose of 25 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 25 ug of RNA encoding a Spike protein from an Omicron variant of SARS-CoV-2. In some embodiments, the first and the second doses are administered on the same day. In some embodiments, a subject is administered a first booster regimen comprising a first dose of 30 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 30 ug of RNA encoding a Spike protein from an Omicron variant of SARS-CoV-2, wherein the first and the second dose are optionally administered on the same day (e.g., in separate administrations or as administration of a multivalent vaccine). In some embodiments, such a first booster regimen is administered to a subject previously administered a primary regimen comprising two doses of 30 ug of RNA, administered about 21 days apart wherein the first booster regimen is administered at least 3 months (e.g., at least 4, at least 5, or at least 6 months) after administration of a primary regimen.

[001309] In some embodiments, a subject is administered a second booster regimen comprising a first dose of 15 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 15 ug of RNA encoding a Spike protein from an Omicron variant of SARS-CoV-2, where the first and the second dose are administered on the same day (e.g., wherein compositions comprising the RNA are mixed prior to administration to form a multivalent vaccine, and the mixture is then administered to a patient). In some embodiments, a subject is administered a second booster regimen comprising a first dose of 25 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 25 ug of RNA encoding a Spike protein from an Omicron variant of SARS- CoV-2, wherein the first dose and the second dose are optionally administered on the same day (e.g., via administration of a multivalent vaccine or via administration of separate compositions). In some embodiments, a subject is administered a second booster regimen comprising a first dose of 25 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 25 ug of RNA encoding a Spike protein from an Omicron variant of SARS-CoV-2. In some embodiments, a subject is administered a second booster regimen comprising a first dose of 30 ug of RNA encoding a Spike protein from a Wuhan variant and a second dose of 30 ug of RNA encoding a Spike protein from an Omicron variant of SARS-CoV-2, wherein the first dose and the second dose are optionally administered on the same day (e.g., via administration of a multivalent vaccine or via administration of separate compositions). In some embodiments, such a second booster regimen is administered to a subject previously administered a primary regimen comprising two doses of 30 ug of RNA, administered about 21 days apart. In some embodiments, such a second booster regimen is administered to a subject previously administered a primary regimen comprising two doses of 30 ug of RNA, administered about 21 days apart, and a first booster regimen comprising a dose of 30 ug of RNA, wherein the second booster regimen is administered at least 3 months (e.g., at least 4, at least 5, or at least 6 months) after administration of a first booster regimen.

[001310] In some embodiments, patients receiving dose(s) of RNA compositions as described herein are monitored for one or more particular conditions, e.g., following administration of one or more doses. In some embodiments, such condition(s) may be or comprise allergic reaction(s) (particularly in subject(s) with a history of relevant allergies or allergic reactions), myocarditis (inflammation of the heart muscle, particularly where the subject is a young male and/or may have experienced prior such inflammation), pericarditis (inflammation of the lining outside the heart, particularly where the subject is a young males and/or may have experienced prior such inflammation), fever, bleeding (particularly where the subject is known to have a bleeding disorder or to be receiving therapy with a blood thinner). Alternatively or additionally, patients who may receive closer monitoring may be or include patients who are immunocompromised or are receiving therapy with a medicine that affects the immune system, are pregnant or planning to become pregnant, are breastfeeding, have received another COVID-19 vaccine, and/or have ever fainted in association with an injection. In some embodiments, patients are monitored for myocarditis following administration of one of the compositions disclosed herein. In some embodiments, patients are monitored for pericarditis following administration of one of the compositions disclosed herein. Patients may be monitored and/or treated for the condition using current standards of care.

[001311] In some embodiments, efficacy for RNA (e.g., mRNA) compositions described in pediatric populations (e.g., described herein) may be assessed by various metrics described herein (including, e.g., but not limited to COVID-19 incidence per 1000 person-years in subjects with no serological or virological evidence of past SARS-CoV-2 infection; geometric mean ratio (GMR) of SARS CoV-2 neutralizing titers measured, e.g., 7 days after a second dose; etc.)

[001312] In some embodiments, pediatric populations described herein (e.g., from 12 to less than 16 years of age) may be monitored for occurrence of multisystem inflammatory syndrome (MIS) (e.g., inflammation in different body parts such as, e.g., heart, lung, kidneys, brain, skin ,eyes, and/or gastrointestinal organs), after administration of an RNA composition (e.g., mRNA) described herein. Exemplary symptoms of MIS in children may include, but are not limited to fever, abdominal pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, feeling extra tried, and combinations thereof.

[001313] In some embodiments, populations to be treated with RNA described herein comprise, essentially consist of, or consist of subjects of age of at least 50, at least 55, at least 60, or at least 65. In some embodiments, populations to be treated with RNA described herein comprise, essentially consist of, or consist of subjects of age of between 55 to 90, 60 to 85, or 65 to 85.

[001314] In some embodiments, the period of time between the doses administered is at least 7 days, at least 14 days, or at least 21 days. In some embodiments, the period of time between the doses administered is between 7 days and 28 days such as between 14 days and 23 days. [001315] In some embodiments, no more than 5 doses, no more than 4 doses, or no more than 3 doses of the RNA described herein may be administered to a subject.

[001316] In some embodiments, the methods and agents described herein are administered (in a regimen, e.g., at a dose, frequency of doses and/or number of doses) such that adverse events (AE), i . e. , any unwanted medical occurrence in a patient, e.g., any unfavourable and unintended sign, symptom, or disease associated with the use of a medicinal product, whether or not related to the medicinal product, are mild or moderate in intensity. In some embodiments, the methods and agents described herein are administered such that adverse events (AE) can be managed with interventions such as treatment with, e.g., paracetamol or other drugs that provide analgesic, antipyretic (fever-reducing) and/or anti-inflammatory effects, e.g., nonsteroidal antiinflammatory drugs (NSAIDs), e.g., aspirin, ibuprofen, and naproxen. Paracetamol or "acetaminophen" which is not classified as a NSAID exerts weak anti-inflammatory effects and can be administered as analgesic according to the present disclosure.

[001317] In some embodiments, the methods and agents described herein provide a neutralizing effect in a subject to coronavirus, coronavirus infection, or to a disease or disorder associated with coronavirus.

[001318] In some embodiments, the methods and agents described herein following administration to a subject induce an immune response that blocks or neutralizes coronavirus in the subject. In some embodiments, the methods and agents described herein following administration to a subject induce the generation of antibodies such as IgG antibodies that block or neutralize coronavirus in the subject. In some embodiments, the methods and agents described herein following administration to a subject induce an immune response that blocks or neutralizes coronavirus S protein binding to ACE2 in the subject. In some embodiments, the methods and agents described herein following administration to a subject induce the generation of antibodies that block or neutralize coronavirus S protein binding to ACE2 in the subject.

[001319] In some embodiments, the methods and agents described herein following administration to a subject induce geometric mean concentrations (GMCs) of RBD domain-binding antibodies such as IgG antibodies of at least 500 U/ml, 1000 U/ml, 2000 U/ml, 3000 U/ml, 4000 U/ml, 5000 U/ml, 10000 U/ml, 15000 U/ml, 20000 U/ml, 25000 U/ml, 30000 U/ml or even higher. In some embodiments, the elevated GMCs of RBD domain-binding antibodies persist for at least 14 days, 21 days, 28 days, 1 month, 3 months, 6 months, 12 months or even longer.

[001320] In some embodiments, the methods and agents described herein following administration to a subject induce geometric mean titers (GMTs) of neutralizing antibodies such as IgG antibodies of at least 100 U/ml, 200 U/ml, 300 U/ml, 400 U/ml, 500 U/ml, 1000 U/ml, 1500 U/ml, or even higher. In some embodiments, the elevated GMTs of neutralizing antibodies persist for at least 14 days, 21 days, 28 days, 1 month, 3 months, 6 months, 12 months or even longer.

[001321] As used herein, the term "neutralization" refers to an event in which binding agents such as antibodies bind to a biological active site of a virus such as a receptor binding protein, thereby inhibiting the viral infection of cells. As used herein, the term "neutralization" with respect to coronavirus, in particular coronavirus S protein, refers to an event in which binding agents such as antibodies bind to the RBD domain of the S protein, thereby inhibiting the viral infection of cells. In particular, the term "neutralization" refers to an event in which binding agents eliminate or significantly reduce virulence (e.g. ability of infecting cells) of viruses of interest. [001322] The type of immune response generated in response to an antigenic challenge can generally be distinguished by the subset of T helper (Th) cells involved in the response. Immune responses can be broadly divided into two types: Thl and Th2. Thl immune activation is optimized for intracellular infections such as viruses, whereas Th2 immune responses are optimized for humoral (antibody) responses. Thl cells produce interleukin 2 (IL-2), tumor necrosis factor (TNFa) and interferon gamma (IFNy). Th2 cells produce IL-4, IL-5, IL- 6, IL-9, IL-10 and IL-13. Thl immune activation is the most highly desired in many clinical situations. Vaccine compositions specialized in eliciting Th2 or humoral immune responses are generally not effective against most viral diseases.

[001323] In some embodiments, the methods and agents described herein following administration to a subject induce or promote a Thl-mediated immune response in the subject. In some embodiments, the methods and agents described herein following administration to a subject induce or promote a cytokine profile that is typical for a Thl-mediated immune response in the subject. In some embodiments, the methods and agents described herein following administration to a subject induce or promote the production of interleukin 2 (IL-2), tumor necrosis factor (TNFo) and/or interferon gamma (IFNy) in the subject. In some embodiments, the methods and agents described herein following administration to a subject induce or promote the production of interleukin 2 (IL-2) and interferon gamma (IFNy) in the subject. In some embodiments, the methods and agents described herein following administration to a subject do not induce or promote a Th2-mediated immune response in the subject, or induce or promote a Th2-mediated immune response in the subject to a significant lower extent compared to the induction or promotion of a Thl-mediated immune response. In some embodiments, the methods and agents described herein following administration to a subject do not induce or promote a cytokine profile that is typical for a Th2-mediated immune response in the subject, or induce or promote a cytokine profile that is typical for a Th2-mediated immune response in the subject to a significant lower extent compared to the induction or promotion of a cytokine profile that is typical for a Thl-mediated immune response. In some embodiments, the methods and agents described herein following administration to a subject do not induce or promote the production of IL-4, IL-5, IL-6, IL-9, IL-10 and/or IL-13, or induce or promote the production of IL-4, IL-5, IL-6, IL-9, IL-10 and/or IL-13 in the subject to a significant lower extent compared to the induction or promotion of interleukin 2 (IL-2), tumor necrosis factor (TNFo) and/or interferon gamma (IFNy) in the subject. In some embodiments, the methods and agents described herein following administration to a subject do not induce or promote the production of IL-4, or induce or promote the production of IL-4 in the subject to a significant lower extent compared to the induction or promotion of interleukin 2 (IL-2) and interferon gamma (IFNy) in the subject.

[001324] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a panel of different S protein variants such as SARS-CoV-2 S protein variants, in particular naturally occurring S protein variants. In some embodiments, the panel of different S protein variants comprises at least 5, at least 10, at least 15, or even more S protein variants. In some embodiments, such S protein variants comprise variants having amino acid modifications in the RBD domain and/or variants having amino acid modifications outside the RBD domain .

[001325] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets VOC-202012/01.

[001326] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets 501.V2.

[001327] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets VOC-202012/01. [001328] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets "Cluster 5".

[001329] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a S protein variant such as SARS-CoV-2 S protein variant, in particular naturally occurring S protein variant comprising a mutation at a position corresponding to position 614 (D) in SEQ ID NO: 1. In one embodiment, the amino acid corresponding to position 614 (D) in SEQ ID NO: 1 is G.

[001330] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets VOC-202012/01.

[001331] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets VOC-202012/01.

[001332] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a S protein variant such as SARS-CoV-2 S protein variant, in particular naturally occurring S protein variant comprising a mutation at a position corresponding to position 484 (E) in SEQ ID NO: 1. In one embodiment, the amino acid corresponding to position 484 (E) in SEQ ID NO: 1 is K.

[001333] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets 501.V2.

[001334] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets "B.l.1.28".

[001335] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets "B.l.1.248".

[001336] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a S protein variant such as SARS-CoV-2 S protein variant, in particular naturally occurring S protein variant comprising a mutation at positions corresponding to positions 501 (N) and 484 (E) in SEQ ID NO: 1. In one embodiment, the amino acid corresponding to position 501 (N) in SEQ ID NO: 1 is Y and the amino acid corresponding to position 484 (E) in SEQ ID NO: 1 is K.

[001337] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets 501.V2.

[001338] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets "B.l.1.248".

[001339] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a S protein variant such as SARS-CoV-2 S protein variant, in particular naturally occurring S protein variant comprising a mutation at positions corresponding to positions 501 (N), 484 (E) and 614 (D) in SEQ ID NO: 1. In one embodiment, the amino acid corresponding to position 501 (N) in SEQ ID NO: 1 is Y, the amino acid corresponding to position 484 (E) in SEQ ID NO: 1 is K and the amino acid corresponding to position 614 (D) in SEQ ID NO: 1 is G.

[001340] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a S protein variant such as SARS-CoV-2 S protein variant, in particular naturally occurring S protein variant comprising a deletion at a position corresponding to positions 242 (L), 243 (A) and 244 (L) in SEQ ID NO: 1.

[001341] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets 501.V2.

[001342] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a S protein variant such as SARS-CoV-2 S protein variant, in particular naturally occurring S protein variant comprising a mutation at a position corresponding to position 417 (K) in SEQ ID NO: 1. In one embodiment, the amino acid corresponding to position 417 (K) in SEQ ID NO: 1 is N. In one embodiment, the amino acid corresponding to position 417 (K) in SEQ ID NO: 1 is T.

[001343] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets 501.V2.

[001344] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets "B.l.1.248".

[001345] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets a S protein variant such as SARS-CoV-2 S protein variant, in particular naturally occurring S protein variant comprising a mutation at positions corresponding to positions 417 (K) and 484 (E) and/or 501 (N) in SEQ ID NO: 1. In one embodiment, the amino acid corresponding to position 417 (K) in SEQ ID NO: 1 is N, and the amino acid corresponding to position 484 (E) in SEQ ID NO: 1 is K and/or the amino acid corresponding to position 501 (N) in SEQ ID NO: 1 is Y. In one embodiment, the amino acid corresponding to position 417 (K) in SEQ ID NO: 1 is T, and the amino acid corresponding to position 484 (E) in SEQ ID NO: 1 is K and/or the amino acid corresponding to position 501 (N) in SEQ ID NO: 1 is Y.

[001346] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets 501.V2.

[001347] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets "B.l.1.248".

[001348] In some embodiments, the methods and agents described herein following administration to a subject induce an antibody response, in particular a neutralizing antibody response, in the subject that targets the Omicron (B.l.1.529) variant.

[001349] In some embodiments, the methods and agents described herein following administration to a subject induce an immune response (cellular and/or antibody response, in particular neutralizing antibody response) in the subject that targets the Omicron (B.l.1.529) variant. [001350] The term "amino acid corresponding to position..." as used herein refers to an amino acid position number corresponding to an amino acid position number in SARS-CoV-2 S protein, in particular the amino acid sequence shown in SEQ ID NO: 1. The phrase "as compared to SEQ ID NO: 1" is equivalent to "at positions corresponding to the following positions in SEQ ID NO: 1". Corresponding amino acid positions in other coronavirus S protein variants such as SARS-CoV-2 S protein variants may be found by alignment with SARS-CoV- 2 S protein, in particular the amino acid sequence shown in SEQ ID NO: 1. It is considered well-known in the art how to align a sequence or segment in a sequence and thereby determine the corresponding position in a sequence to an amino acid position according to the present disclosure. Standard sequence alignment programs such as ALIGN, ClustalW or similar, typically at default settings may be used.

[001351] In some embodiments, a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, e.g., as encoded by the RNA described herein, comprises one or more of the mutations described herein for S protein variants such as SARS-CoV-2 S protein variants, in particular naturally occurring S protein variants. In one embodiment, a SARS- CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, e.g., as encoded by the RNA described herein, comprises a mutation at a position corresponding to position 501 (N) in SEQ ID NO: 1. In one embodiment, the amino acid corresponding to position 501 (N) in SEQ ID NO: 1 is Y. In some embodiments, a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, e.g., as encoded by the RNA described herein, comprises one or more mutations, such as all mutations, of a SARS-CoV-2 S protein of a SARS-CoV-2 variant selected from the group consisting of VOC-202012/01, 501.V2, Cluster 5 and B.1.1.248. In some embodiments, a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, e.g., as encoded by the RNA described herein, comprises an amino acid sequence with alanine substitution at position 80, glycine substitution at position 215, lysine substitution at position 484, tyrosine substitution at position 501, valine substitution at position 701, phenylalanine substitution at position 18, isoleucine substitution at position 246, asparagine substitution at position 417, glycine substitution at position 614, deletions at positions 242 to 244, and proline substitutions at positions 986 and 987 of SEQ ID NO:1.

[001352] In some embodiments, a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, e.g., as encoded by the RNA described herein, comprising said mutations comprises K986P and V987P, as compared to SEQ ID NO: 1. [001353] In some embodiments, a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, e.g., as encoded by the RNA described herein, comprising said mutations comprises K986P and V987P, as compared to SEQ ID NO: 1. [001354] In some embodiments, administration of a variant specific vaccine (e.g., a variant specific vaccine disclosed herein) may result in an improved immune response in a patient as compared to administration of vaccine encoding or comprising a SARS-CoV-2 S protein from a Wuhan strain, or an immunogenic fragment thereof. In some embodiments, administration of a variant-specific vaccine may result in induction of a broader immune response in a subject as compared to a patient administered a vaccine comprising or encoding a SARS- CoV-2 S protein from a Wuhan strain (or an immunogenic fragment thereof) (e.g., induce a stronger neutralization response against a greater number of SARS-CoV-2 variants and/or a neutralization response that recognizes epitopes in a greater number of SARS-CoV-2 variants). In particular embodiments, a broader immune response may be induced when a variant specific vaccine is administered in combination with a vaccine comprising or encoding a SARS-CoV-2 S protein from a different variant or from a Wuhan strain (e.g., in some embodiments, a broader immune response may be induced when a variant specific vaccine is administered in combination with a vaccine comprising or encoding a SARS-CoV-2 S protein from a Wuhan strain or a vaccine comprising or encoding a SARS-CoV-2 S protein comprising mutations characteristic of a different SARS-CoV-2 variant). For example, a broader immune response may be induced when an RNA vaccine encoding a SARS-CoV- 2 S protein from a Wuhan strain is administered in combination with an RNA vaccine encoding a SARS-CoV-2 S protein having mutations characteristic of an Omicron variant. In another embodiment, a broader immune response may be induced when an RNA vaccine encoding a SARS-CoV-2 S protein comprising one or more mutations characteristic of a delta variant is administered in combination with an RNA vaccine encoding a SARS- CoV-2 S protein comprising one or more mutations characteristic of an Omicron variant. In such embodiments, a "broader" immune response may be defined relative to a patient administered a vaccine comprising or encoding a SARS-CoV-2 S protein from a single variant (e.g., an RNA vaccine encoding a SARS-CoV-2 S protein from a Wuhan strain). Vaccines comprising or encoding S proteins from different SARS-CoV-2 variants, or immunogenic fragments thereof, may be administered in combination by administering at different time points (e.g., administering a vaccine encoding a SARS-CoV-2 S protein from a Wuhan strain and a vaccine encoding a SARS- CoV-2 S protein having one or more mutations characteristic of a variant strain at different time points, e.g., both administered as part of a primary regimen or part of a booster regimen; or one is administered as part of a primary regimen while another is administered as part of a booster regimen). In some embodiments, vaccines comprising or encoding S proteins from different SARS-CoV-2 variants, or immunogenic fragments thereof, may be administered in combination by administering a multivalent vaccine (e.g., a composition comprising RNA encoding a SARS-CoV-2 S protein from a Wuhan strain and RNA encoding a SARS-CoV-2 S protein having mutations characteristic of an Omicron variant). In some embodiments, a variant specific vaccine may induce a superior immune response (e.g., inducing higher concentrations of neutralizing antibodies) against a variant against which the vaccine is specifically designed to immunize, and an immune response against one or more other variants. In some such embodiments, an immune response against other variant(s) may be comparable to or higher than that as observed with a vaccine that encodes or comprises a SARS-CoV-2 S protein from a Wuhan strain.

[001355] In some embodiments, the geometric mean ratio (GMR) or geometric mean fold rise (GMFR) of neutralization antibodies induced by a variant specific vaccine is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0 (e.g., 1.1 to 4, 1.1 to 3.5, 1.1 to 3, 1.5 to 3, or 1.1 to 1.5) fold higher than that induced by a non-variant specific vaccine (e.g., as measured 1 day to 3 months after immunization, 7 days to 2 months after administration, about 7 days, or about 1 month after administration).

[001356] In some embodiments, the methods and agents, e.g., RNA (e.g., mRNA) compositions, described herein following administration to a subject induce a cell-mediated immune response (e.g., CD4+ and/or CD8+ T cell response). In some embodiments, T cells are induced that recognize one or more epitopes (e.g., MHC class I- restricted epitopes) selected from the group consisting of LPFNDGVYF, GVYFASTEK, YLQPRTFLL, QPTESIVRF, CVADYSVLY, KCYGVSPTK, NYNYLYRLF, FQPTNGVGY, IPFAMQMAY, RLQSLQTYV, GTHWFVTQR, VYDPLQPEL, QYIKWPWYI, and KWPWYIWLGF. In one embodiment, T cells are induced that recognize the epitope YLQPRTFLL. In one embodiment, T cells are induced that recognize the epitope NYNYLYRLF. In one embodiment, T cells are induced that recognize the epitope QYIKWPWYI. In one embodiment, T cells are induced that recognize the epitope KCYGVSPTK. In one embodiment, T cells are induced that recognize the epitope RLQSLQTYV. In some embodiments, the methods and agents, e.g., RNA (e.g., mRNA) compositions, described herein are administered according to a regimen which achieves such induction of T cells.

[001357] In some embodiments, the methods and agents, e.g., RNA (e.g., mRNA) compositions, described herein following administration to a subject induce a cell-mediated immune response (e.g., CD4+ and/or CD8+ T cell response) that is detectable 15 weeks or later, 16 weeks or later, 17 weeks or later, 18 weeks or later, 19 weeks or later, 20 weeks or later, 21 weeks or later, 22 weeks or later, 23 weeks or later, 24 weeks or later or 25 weeks or later after administration, e.g., using two doses of the RNA described herein (wherein the second dose may be administered about 21 days following administration of the first dose). In some embodiments, the methods and agents, e.g., RNA (e.g., mRNA) compositions, described herein are administered according to a regimen which achieves such induction of a cell-mediated immune response.

[001358] In one embodiment, vaccination against Coronavirus described herein, e.g., using RNA described herein which may be administered in the amounts and regimens described herein, e.g., at two doses of 30 pg per dose e.g. administered 21 days apart, may be repeated after a certain period of time, e.g., once it is observed that protection against Coronavirus infection diminishes, using the same or a different vaccine as used for the first vaccination. Such certain period of time may be at least 6 months, 1 year, two years etc. In one embodiment, the same RNA as used for the first vaccination is used for the second or further vaccination, however, at a lower dose or a lower frequency of administration. For example, the first vaccination may comprise vaccination using a dose of about 30 μg per dose, wherein in one embodiment, at least two of such doses are administered, (for example, a second dose may be administered about 21 days following administration of the first dose) and the second or further vaccination may comprise vaccination using a dose of less than about 30 pg per dose, wherein in one embodiment, only one of such doses is administered. In one embodiment, a different RNA as used for the first vaccination is used for the second or further vaccination, e.g., BNT162b2 is used for the first vaccination and BNT162B1 or BNT162b3 is used for the second or further vaccination.

[001359] In one embodiment, the vaccination regimen comprises a first vaccination using at least two doses of the RNA described herein, e.g., two doses of the RNA described herein (wherein the second dose may be administered about 21 days following administration of the first dose), and a second vaccination using a single dose or multiple doses, e.g., two doses, of the RNA described herein. In various embodiments, the second vaccination is administered 3 to 24 months, 6 to 18 months, 6 to 12 months, or 5 to 7 months after administration of the first vaccination, e.g., after the initial two-dose regimen. The amount of RNA used in each dose of the second vaccination may be equal or different to the amount of RNA used in each dose of the first vaccination. In one embodiment, the amount of RNA used in each dose of the second vaccination is equal to the amount of RNA used in each dose of the first vaccination. In one embodiment, the amount of RNA used in each dose of the second vaccination and the amount of RNA used in each dose of the first vaccination is about 30 pg per dose. In one embodiment, the same RNA as used for the first vaccination is used for the second vaccination. [001360] In one embodiment, the RNA used for the first vaccination and for the second vaccination is BNT162b2.

[001361] In some embodiments, when the RNA used for the first vaccination and for the second vaccination is BNT162b2, the aim is to induce an immune response that targets SARS-CoV-2 variants including, but not limited to, an Omicron (B.l.1.529) variant. Accordingly, in some embodiments, when the RNA used for the first vaccination and for the second vaccination is BNT162b2, the aim is to protect a subject from infection with SARS- CoV-2 variants including, but not limited to, the Omicron (B.l.1.529) variant.

[001362] In one embodiment, a different RNA as used for the first vaccination is used for the second vaccination. In one embodiment, the RNA used for the first vaccination is BNT162b2 and the RNA used for the second vaccination is RNA encoding a SARS-CoV-2 S protein of a SARS-CoV-2 variant strain, e.g., a strain discussed herein. In one embodiment, the RNA used for the first vaccination is BNT162b2 and the RNA used for the second vaccination is RNA encoding a SARS-CoV-2 S protein of a SARS-CoV-2 variant strain that is prevalent or rapidly spreading at the time of the second vaccination. In one embodiment, the RNA used for the first vaccination is BNT162b2 and the RNA used for the second vaccination is RNA encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprising one or more of the mutations described herein for S protein variants such as SARS- CoV-2 S protein variants, in particular naturally occurring S protein variants. In one embodiment, the RNA used for the first vaccination is BNT162b2 and the RNA used for the second vaccination is RNA encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprising one or more mutations, such as all mutations, of a SARS-CoV-2 S protein of a SARS-CoV-2 variant selected from the group consisting of VOC-202012/01, 501. V2, Cluster 5, B.1.1.248, and Omicron (B.1.1.529).

[001363] In one embodiment, the vaccination regimen comprises a first vaccination using two doses of RNA encoding a polypeptide comprising an amino acid sequence with proline residue substitutions at positions 986 and 987 of SEQ ID NO:1 administered about 21 days apart and a second vaccination using a single dose or multiple doses of RNA encoding a polypeptide comprising an amino acid sequence with proline residue substitutions at positions 986 and 987 of SEQ ID NO:1 administered about 4 to 12 months, 5 to 12 months, or 6 to 12 months after administration of the first vaccination, i.e., after the initial two-dose regimen. In one embodiment, each RNA dose comprises 30 μg RNA. In this embodiment, the aim in one embodiment is to induce an immune response that targets SARS-CoV-2 variants including, but not limited to, an Omicron (B.1.1.529) variant. Accordingly, in this embodiment, the aim in one embodiment is to protect a subject from infection with SARS-CoV-2 variants including, but not limited to, an Omicron (B.l.1.529) variant.

[001364] In one embodiment, the second vaccination results in a boosting of the immune response. [001365] In one embodiment, RNA described herein is co-administered with other vaccines. In some embodiments, RNA described herein is co-administered with a composition comprising one or more T-cell epitopes of SARS-CoV-2 or RNA encoding the same. In some embodiments, RNA described herein is coadministered one or more T-cell epitopes, or RNA encoding the same, derived from an M protein, an N protein, and/or an ORFlab protein of SARS-CoV-2, e.g., a composition disclosed in WO2021188969, the contents of which is incorporated by reference herein in its entirety. In some embodiments, RNA described herein (e.g., RNA encoding a SARS-CoV-2 S protein comprising mutations characteristic of a BA.l, BA.2, or BA.4/5 Omicron variant, optionally administered with RNA encoding a SARS-CoV-2 S protein of a Wuhan variant) is co-administered with a T-string construct described in WO2021188969 (e.g., an RNA encoding SEQ ID NO: RS C7p2full of WO2021/188969). In some embodiments, RNA described herein and a T-string construct described in WO2021188969 are administered in a combination of up to about 100 ug RNA total. In some embodiments, subjects are administered with at least 2 doses of RNA described herein (e.g., in some embodiments at 30 ug each) in combination with a T-string construct (e.g., an RNA encoding SEQ ID NO: RS C7p2full of

WO2021/188969), e.g., each dose of a combination of RNA described herein and an RNA encoding SEQ ID NO: RS C7p2full of up to about 100 ug RNA total, wherein the two doses are administered, for example, at least 4 weeks or longer (including, e.g., at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, or at least 12 weeks, or longer) apart from one another. In some embodiments, subjects are administered at least 3 doses of RNA described herein (e.g., in some embodiments at 30 ug each) in combination with a T-string construct (e.g., an RNA encoding SEQ ID NO: RS C7p2full of WO2021/188969), e.g., each dose of a combination of RNA described herein and an RNA encoding SEQ ID NO: RS C7p2full of up to about 100 ug RNA total, wherein the first and the second doses and the second and third doses are each independently administered at least 4 weeks or longer (including, e.g., at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, or at least 12 weeks, or longer) apart from one another. In some embodiments, the RNA described herein and the T-string construct may be co-administered as separate formulations (e.g., formulations administered on the same day to separate injection sites). In some embodiments, the RNA described herein and the T-string construct may be co- administered as a co-formulation (e.g., a formulation comprising RNA described herein and the T-string construct as separate LNP formulations or as LNP formulations comprising both a T-string construct and RNA described herein).

[001366] In some embodiments, an RNA composition described herein is co-administered with one or more vaccines against a non-SARS-CoV-2 disease. In some embodiments, an RNA composition described herein is coadministered with one or more vaccines against a non-SARS-COV-2 viral disease. In some embodiments, an RNA composition described herein is co-administered with one or more vaccines against a non-SARS-CoV-2 respiratory disease. In some embodiments, the non-SARS-CoV-2 respiratory disease is a non-SARS-CoV-2 Coronavirus, an Influenza virus, a Pneumoviridae virus, or a Paramyxoviridae virus. In some embodiments, the Pneumoviridae virus is a Respiratory syncytial virus or a Metapneumovirus. In some embodiments, the Metapneumovirus is a human metapneumovirus (hMPV). In some embodiments, the Paramyxoviridae virus is a Parainfluenza virus or a Henipavirus. In some embodiments the parainfluenzavirus is PIV3. In some embodiments, the non-SARS-CoV-2 coronavirus is a betacoronavirus (e.g., SARS-CoV-1). In come embodiments the non-SARS-CoV-2 coronavirus is a Merbecovirus (e.g., a MERS-CoV virus).

[001367] In some embodiments, an RNA composition described herein is co-administered with an RSV vaccine (e.g., an RSV A or RSV B vaccine). In some embodiments, the RSV vaccine comprises an RSV fusion protein (F), an RSV attachment protein (G), an RSV small hydrophobic protein (SH), an RSV matrix protein (M), an RSV nucleoprotein (N), an RSV M2-1 protein, an RSV Large polymerase (L), and/or an RSV phosphoprotein (P), or an immunogenic fragment of immunogenic variant thereof, or a nucleic acid (e.g., RNA), encoding any one of the same.

[001368] Numerous RSV vaccines are known in the art, any one of which can be co-administered with an RNA composition described herein. See, for example, the list of RSV vaccines provided on the website of PATH, a global health organization (see httx^://www.path.org/res(Xirces/rsv-vaccine- snapshot/), as well as in

Mazur, Natalie I., et al, "The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates," The Lancet Infectious Diseases 18.10 (2018): e295-e311, the contents of each of which is incorporated by reference herein. In some embodiments, an RNA composition described herein is coadministered with an RSV vaccine that has been previously published on (e.g., an RSV vaccine described on the PATH website page linked to above, or in Mazur et al.). In some embodiments, an RNA composition described herein is co-administered with a live-attenuated or chimeric vaccine (e.g., rBCG-N-hRSV (developed by Ponteificia Uinersidad Catolica de Chile), RSV D46 cp AM202 (developed by Sanofi Pasteur/LID/NIAD/NIH), RSV LID AM2-2 1030s (developed by Sanofi Pasteur/LID/NIAD/NIH), RSV ANS2 A1313/I1314L (developed by Sanofi Pasteur/LID/NIAD/NIH), RSV D46 ANS2 N AM2-2 Hindlll (developed by Sanofi Pasteur/LID/NIAD/NIH) or RSV LID AM2-2 1030s (developed by Sanofi Pasteur/LID/NIAD/NIH), MV-012-968 (developed by Meissa Vaccines), SP0125 (developed by Sanofi), blb201 (developed by Blue lake), CodaVax™-RSV (developed by Cadagenix), RSVDeltaG (developed by Intravacc), or SeVRSV (developed by SIHPL and St. Jude hospital), a particle based vaccine (e.g., RSV F nanoparticle (developed by Novavax) or SynGEM (developed by Mucosis), Icosavzx (developed by IVX-121), or V-306 (developed by Virometix)), a subunit vaccine (e.g., GSK RSV F (developed by GSK), Arexvy (developed by GSK), DPX-RSV (developed by Dalousie Univeristy, Immunovaccine, and VIB), RSV F DS-Cavl (developed by NIH/NIAID/VRC), MEDI-7510 (developed by Medlmmune), RSVpreF (developed by Pfizer), ADV110 (developed by Advaccine), VN-0200 (developed by Daiichi Sankyo, Inc.)), a vector vaccine (e.g., MVA-BN RSV (developed by Banarian Nordic), VXA-RSVf oral (developed by Vaxart), Ad26.RSV.pref (developed by Janssen), ChAdl55-RSV (developed by GSK) Immunovaccine, DPX-RSV (developed by VIB), or DS-Cavl (developed by NIH/NIAID/VRC) or a nucleic acid vaccine (e.g., an mRNA vaccine being developed by CureVac (currently unnamed) or mRNA-1345 (developed by Moderna), or SP0274 (developed by Sanofi)). [001369] In some embodiments, an RNA composition described herein is co-administered with an influenza vaccine. In some embodiments, the influenza vaccine is an alphainfluenza virus, a betainfluenza virus, a gammainfluenza virus or a deltainfluenza virus vaccine. In some embodiments the vaccine is an Influenza A virus, an Influenza B virus, an Influenza C virus, or an Influenza D virus vaccine. In some embodiments, the influenza A virus vaccine comprises a hemagglutinin selected from Hl, H2, H3, H4, H5, H6, H7, H8, H9, H10, Hll, H12, H13, H14, H15, H16, H17, and H18, or an immunogenic fragment or variant of the same, or a nucleic acid (e.g., RNA) encoding any one of the same. In some embodiments the influenza A vaccine comprises or encodes a neuraminidase (NA) selected from Nl, N2, N3, N4, N5, N6, N7, N8, N9, N10, and Nil, or an immunogenic fragment or variant of the same, or a nucleic acid (e.g., RNA) encoding any one of the same. In some embodiments, the influenza vaccine comprises at least one Influenza virus hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix protein 1 (Ml), matrix protein 2 (M2), non-structural protein 1 (NS1 ), non-structural protein 2 (NS2), nuclear export protein (NEP), polymerase acidic protein (PA), polymerase basic protein PB1, PB1-F2, and/or polymerase basic protein 2 (PB2), or an immunogenic fragment or variant thereof, or a nucleic acid (e.g., RNA) encoding any of one of the same.

[001370] In some embodiments, an RNA composition described herein can be co-administered with a commercially approved influenza vaccine. In some embodiments, an RNA composition described herein can be co-administered with an inactivated influenza virus (e.g., Fluzone®, Fluzone high-dose quadrivalent®, Fluzone quadrivalent®, Fluzone intradermal quardivalent®, Fluzone quadrivalent southern hemisphere®, Fluad®, Fluad quadrivalent®, Afluria Quardivalent®, Fluarix Quadrivalent®, FluLaval Quadrivalent®, or Flucelvax Quadrivalent®), a recombinant influenza vaccine (e.g., Flublok quadrivalent®), a live attenuated influenza vaccine (e.g., FluMist Quadrivalent®), a non-adjuvanted influenza vaccine, an adjuvanted influenza vaccine, or a subunit or split vaccine.

[001371] In some embodiments, an RNA composition described herein is co-administered with an influenza vaccine and/or an RSV vaccine.

[001372] In some embodiments, an RNA composition provided herein and other injectable vaccine(s) are administered at different times. In some embodiments, an RNA composition provided herein is administered at the same time as other injectable vaccine(s). In some such embodiments, an RNA composition provided herein and at least one another injectable vaccine(s) are administered at different injection sites. In some embodiments, an RNA composition provided herein is not mixed with any other vaccine in the same syringe. In some embodiments, an RNA composition provided herein is not combined with other coronavirus vaccines as part of vaccination against coronavirus, e.g., SARS-CoV-2.

[001373] The term "disease" refers to an abnormal condition that affects the body of an individual. A disease is often construed as a medical condition associated with specific symptoms and signs. A disease may be caused by factors originally from an external source, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune diseases. In humans, "disease" is often used more broadly to refer to any condition that causes pain, dysfunction, distress, social problems, or death to the individual afflicted, or similar problems for those in contact with the individual. In this broader sense, it sometimes includes injuries, disabilities, disorders, syndromes, infections, isolated symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts and for other purposes these may be considered distinguishable categories. Diseases usually affect individuals not only physically, but also emotionally, as contracting and living with many diseases can alter one's perspective on life, and one's personality.

[001374] In the present context, the term "treatment", "treating" or "therapeutic intervention" relates to the management and care of a subject for the purpose of combating a condition such as a disease or disorder. The term is intended to include the full spectrum of treatments for a given condition from which the subject is suffering, such as administration of the therapeutically effective compound to alleviate the symptoms or complications, to delay the progression of the disease, disorder or condition, to alleviate or relief the symptoms and complications, and/or to cure or eliminate the disease, disorder or condition as well as to prevent the condition, wherein prevention is to be understood as the management and care of an individual for the purpose of combating the disease, condition or disorder and includes the administration of the active compounds to prevent the onset of the symptoms or complications.

[001375] The term "therapeutic treatment" relates to any treatment which improves the health status and/or prolongs (increases) the lifespan of an individual. Said treatment may eliminate the disease in an individual, arrest or slow the development of a disease in an individual, inhibit or slow the development of a disease in an individual, decrease the frequency or severity of symptoms in an individual, and/or decrease the recurrence in an individual who currently has or who previously has had a disease.

[001376] The terms "prophylactic treatment" or "preventive treatment" relate to any treatment that is intended to prevent a disease from occurring in an individual. The terms "prophylactic treatment" or "preventive treatment" are used herein interchangeably.

[001377] The terms "individual" and "subject" are used herein interchangeably. They refer to a human or another mammal (e.g. mouse, rat, rabbit, dog, cat, cattle, swine, sheep, horse or primate) that can be afflicted with or is susceptible to a disease or disorder but may or may not have the disease or disorder. In many embodiments, the individual is a human being. Unless otherwise stated, the terms "individual" and "subject" do not denote a particular age, and thus encompass adults, elderlies, children, and newborns. In some embodiments, the term "subject" includes humans of age of at least 50, at least 55, at least 60, at least 65, at least 70, or older. In some embodiments, the term "subject" includes humans of age of at least 65, such as 65 to 80, 65 to 75, or 65 to 70. In embodiments of the present disclosure, the "individual" or "subject" is a "patient". [001378] The term "patient" means an individual or subject for treatment, in particular a diseased individual or subject.

[001379] In one embodiment of the present disclosure, the aim is to provide an immune response against coronavirus, and to prevent or treat coronavirus infection.

[001380] A pharmaceutical composition comprising RNA encoding a peptide or protein comprising an epitope may be administered to a subject to elicit an immune response against an antigen comprising said epitope in the subject which may be therapeutic or partially or fully protective. A person skilled in the art will know that one of the principles of immunotherapy and vaccination is based on the fact that an immunoprotective reaction to a disease is produced by immunizing a subject with an antigen or an epitope, which is immunologically relevant with respect to the disease to be treated. Accordingly, pharmaceutical compositions described herein are applicable for inducing or enhancing an immune response. Pharmaceutical compositions described herein are thus useful in a prophylactic and/or therapeutic treatment of a disease involving an antigen or epitope.

[001381] As used herein, "immune response" refers to an integrated bodily response to an antigen or a cell expressing an antigen and refers to a cellular immune response and/or a humoral immune response. The immune system is divided into a more primitive innate immune system, and acquired or adaptive immune system of vertebrates, each of which contains humoral and cellular components.

[001382] "Cell-mediated immunity", "cellular immunity", "cellular immune response", or similar terms are meant to include a cellular response directed to cells characterized by expression of an antigen, in particular characterized by presentation of an antigen with class I or class II MHC. The cellular response relates to immune effector cells, in particular to cells called T cells or T lymphocytes which act as either "helpers" or "killers". The helper T cells (also termed CD4+ T cells) play a central role by regulating the immune response and the killer cells (also termed cytotoxic T cells, cytolytic T cells, CD8+ T cells or CTLs) kill diseased cells such as virus-infected cells, preventing the production of more diseased cells.

[001383] An immune effector cell includes any cell which is responsive to vaccine antigen. Such responsiveness includes activation, differentiation, proliferation, survival and/or indication of one or more immune effector functions. The cells include, in particular, cells with lytic potential, in particular lymphoid cells, and are preferably T cells, in particular cytotoxic lymphocytes, preferably selected from cytotoxic T cells, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells. Upon activation, each of these cytotoxic lymphocytes triggers the destruction of target cells. For example, cytotoxic T cells trigger the destruction of target cells by either or both of the following means. First, upon activation T cells release cytotoxins such as perforin, granzymes, and granulysin. Perforin and granulysin create pores in the target cell, and granzymes enter the cell and trigger a caspase cascade in the cytoplasm that induces apoptosis (programmed cell death) of the cell. Second, apoptosis can be induced via Fas-Fas ligand interaction between the T cells and target cells.

[001384] The term "effector functions" in the context of the present disclosure includes any functions mediated by components of the immune system that result, for example, in the neutralization of a pathogenic agent such as a virus and/or in the killing of diseased cells such as virus-infected cells. In one embodiment, the effector functions in the context of the present disclosure are T cell mediated effector functions. Such functions comprise in the case of a helper T cell (CD4+ T cell) the release of cytokines and/or the activation of CD8+ lymphocytes (CTLs) and/or B cells, and in the case of CTL the elimination of cells, i.e., cells characterized by expression of an antigen, for example, via apoptosis or perforin-mediated cell lysis, production of cytokines such as IFN-y and TNF-o, and specific cytolytic killing of antigen expressing target cells.

[001385] The term "immune effector cell" or "immunoreactive cell" in the context of the present disclosure relates to a cell which exerts effector functions during an immune reaction. An "immune effector cell" in one embodiment is capable of binding an antigen such as an antigen presented in the context of MHC on a cell or expressed on the surface of a cell and mediating an immune response. For example, immune effector cells comprise T cells (cytotoxic T cells, helper T cells, tumor infiltrating T cells), B cells, natural killer cells, neutrophils, macrophages, and dendritic cells. Preferably, in the context of the present disclosure, "immune effector cells" are T cells, preferably CD4+ and/or CD8+ T cells, most preferably CD8+ T cells. According to the present disclosure, the term "immune effector cell" also includes a cell which can mature into an immune cell (such as T cell, in particular T helper cell, or cytolytic T cell) with suitable stimulation. Immune effector cells comprise CD34+ hematopoietic stem cells, immature and mature T cells and immature and mature B cells. The differentiation of T cell precursors into a cytolytic T cell, when exposed to an antigen, is similar to clonal selection of the immune system.

[001386] A "lymphoid cell" is a cell which is capable of producing an immune response such as a cellular immune response, or a precursor cell of such cell, and includes lymphocytes, preferably T lymphocytes, lymphoblasts, and plasma cells. A lymphoid cell may be an immune effector cell as described herein. A preferred lymphoid cell is a T cell.

[001387] The terms "T cell" and "T lymphocyte" are used interchangeably herein and include T helper cells (CD4+ T cells) and cytotoxic T cells (CTLs, CD8+ T cells) which comprise cytolytic T cells. The term "antigenspecific T cell" or similar terms relate to a T cell which recognizes the antigen to which the T cell is targeted and preferably exerts effector functions of T cells.

[001388] T cells belong to a group of white blood cells known as lymphocytes, and play a central role in cell- mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptor (TCR). The thymus is the principal organ responsible for the maturation ofT cells. Several different subsets of T cells have been discovered, each with a distinct function.

[001389] T helper cells assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and activation of cytotoxic T cells and macrophages, among other functions. These cells are also known as CD4+ T cells because they express the CD4 glycoprotein on their surface. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules that are expressed on the surface of antigen presenting cells (APCs). Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response.

[001390] Cytotoxic T cells destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein on their surface. These cells recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body.

[001391] A majority of T cells have a T cell receptor (TCR) existing as a complex of several proteins. The TCR of a T cell is able to interact with immunogenic peptides (epitopes) bound to major histocompatibility complex (MHC) molecules and presented on the surface of target cells. Specific binding of the TCR triggers a signal cascade inside the T cell leading to proliferation and differentiation into a maturated effector T cell. The actual T cell receptor is composed of two separate peptide chains, which are produced from the independent T cell receptor alpha and beta (TCRa and TCR(3) genes and are called a- and g-TCR chains. y3 T cells (gamma delta T cells) represent a small subset of T cells that possess a distinct T cell receptor (TCR) on their surface. However, in y3 T cells, the TCR is made up of one y-chain and one 6-chain. This group of T cells is much less common (2% of total T cells) than the a[3 T cells.

[001392] "Humoral immunity" or "humoral immune response" is the aspect of immunity that is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides. It contrasts with cell-mediated immunity. Its aspects involving antibodies are often called antibody-mediated immunity.

[001393] Humoral immunity refers to antibody production and the accessor/ processes that accompany it, including: Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation and memory cell generation. It also refers to the effector functions of antibodies, which include pathogen neutralization, classical complement activation, and opsonin promotion of phagocytosis and pathogen elimination.

[001394] In humoral immune response, first the B cells mature in the bone marrow and gain B-cell receptors (BCR's) which are displayed in large number on the cell surface. These membrane-bound protein complexes have antibodies which are specific for antigen detection. Each B cell has a unique antibody that binds with an antigen. The mature B cells migrate from the bone marrow to the lymph nodes or other lymphatic organs, where they begin to encounter pathogens. When a B cell encounters an antigen, the antigen is bound to the receptor and taken inside the B cell by endocytosis. The antigen is processed and presented on the B cell's surface again by MHC-II proteins. The B cell waits for a helper T cell (TH) to bind to the complex. This binding will activate the TH cell, which then releases cytokines that induce B cells to divide rapidly, making thousands of identical clones of the B cell. These daughter cells either become plasma cells or memory cells. The memory B cells remain inactive here; later when these memory B cells encounter the same antigen due to reinfection, they divide and form plasma cells. On the other hand, the plasma cells produce a large number of antibodies which are released free into the circulatory system. These antibodies will encounter antigens and bind with them. This will either interfere with the chemical interaction between host and foreign cells, or they may form bridges between their antigenic sites hindering their proper functioning, or their presence will attract macrophages or killer cells to attack and phagocytose them.

[001395] The term "antibody" includes an immunoglobulin comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. Each light chain is comprised of a light chain variable region (abbreviated herein as VL) and a light chain constant region. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. An antibody binds, preferably specifically binds with an antigen.

[001396] Antibodies expressed by B cells are sometimes referred to as the BCR (B cell receptor) or antigen receptor. The five members included in this class of proteins are IgA, IgG, IgM, IgD, and IgE. IgA is the primary antibody that is present in body secretions, such as saliva, tears, breast milk, gastrointestinal secretions and mucus secretions of the respiratory and genitourinary tracts. IgG is the most common circulating antibody. IgM is the main immunoglobulin produced in the primary immune response in most subjects. It is the most efficient immunoglobulin in agglutination, complement fixation, and other antibody responses, and is important in defense against bacteria and viruses. IgD is the immunoglobulin that has no known antibody function, but may serve as an antigen receptor. IgE is the immunoglobulin that mediates immediate hypersensitivity by causing release of mediators from mast cells and basophils upon exposure to allergen.

[001397] An "antibody heavy chain", as used herein, refers to the larger of the two types of polypeptide chains present in antibody molecules in their naturally occurring conformations.

[001398] An "antibody light chain", as used herein, refers to the smaller of the two types of polypeptide chains present in antibody molecules in their naturally occurring conformations, K and A light chains refer to the two major antibody light chain isotypes.

[001399] The present disclosure contemplates an immune response that may be protective, preventive, prophylactic and/or therapeutic. As used herein, "induces [or inducing] an immune response" may indicate that no immune response against a particular antigen was present before induction or it may indicate that there was a basal level of immune response against a particular antigen before induction, which was enhanced after induction. Therefore, "induces [or inducing] an immune response" includes "enhances [or enhancing] an immune response".

[001400] The term "immunotherapy" relates to the treatment of a disease or condition by inducing, or enhancing an immune response. The term "immunotherapy" includes antigen immunization or antigen vaccination.

[001401] The terms "immunization" or "vaccination" describe the process of administering an antigen to an individual with the purpose of inducing an immune response, for example, for therapeutic or prophylactic reasons. [001402] The term "macrophage" refers to a subgroup of phagocytic cells produced by the differentiation of monocytes. Macrophages which are activated by inflammation, immune cytokines or microbial products nonspecifically engulf and kill foreign pathogens within the macrophage by hydrolytic and oxidative attack resulting in degradation of the pathogen. Peptides from degraded proteins are displayed on the macrophage cell surface where they can be recognized by T cells, and they can directly interact with antibodies on the B cell surface, resulting in T and B cell activation and further stimulation of the immune response. Macrophages belong to the class of antigen presenting cells. In one embodiment, the macrophages are splenic macrophages.

[001403] The term "dendritic cell" (DC) refers to another subtype of phagocytic cells belonging to the class of antigen presenting cells. In one embodiment, dendritic cells are derived from hematopoietic bone marrow progenitor cells. These progenitor cells initially transform into immature dendritic cells. These immature cells are characterized by high phagocytic activity and low T cell activation potential. Immature dendritic cells constantly sample the surrounding environment for pathogens such as viruses and bacteria. Once they have come into contact with a presentable antigen, they become activated into mature dendritic cells and begin to migrate to the spleen or to the lymph node. Immature dendritic cells phagocytose pathogens and degrade their proteins into small pieces and upon maturation present those fragments at their cell surface using MHC molecules.

Simultaneously, they upregulate cell-surface receptors that act as co-receptors in T cell activation such as CD80, CD86, and CD40 greatly enhancing their ability to activate T cells. They also upregulate CCR7, a chemotactic receptor that induces the dendritic cell to travel through the blood stream to the spleen or through the lymphatic system to a lymph node. Here they act as antigen-presenting cells and activate helper T cells and killer T cells as well as B cells by presenting them antigens, alongside non-antigen specific co-stimulatory signals. Thus, dendritic cells can actively induce a T cell- or B cell-related immune response. In one embodiment, the dendritic cells are splenic dendritic cells.

[001404] The term "antigen presenting cell" (APC) is a cell of a variety of cells capable of displaying, acquiring, and/or presenting at least one antigen or antigenic fragment on (or at) its cell surface. Antigen- presenting cells can be distinguished in professional antigen presenting cells and non-professional antigen presenting cells.

[001405] The term "professional antigen presenting cells" relates to antigen presenting cells which constitutively express the Major Histocompatibility Complex class II (MHC class II) molecules required for interaction with naive T cells. If a T cell interacts with the MHC class II molecule complex on the membrane of the antigen presenting cell, the antigen presenting cell produces a co-stimulatory molecule inducing activation of the T cell. Professional antigen presenting cells comprise dendritic cells and macrophages.

[001406] The term "non-professional antigen presenting cells" relates to antigen presenting cells which do not constitutively express MHC class II molecules, but upon stimulation by certain cytokines such as interferongamma. Exemplary, non-professional antigen presenting cells include fibroblasts, thymic epithelial cells, thyroid epithelial cells, glial cells, pancreatic beta cells or vascular endothelial cells.

[001407] "Antigen processing" refers to the degradation of an antigen into procession products, which are fragments of said antigen (e.g., the degradation of a protein into peptides) and the association of one or more of these fragments (e.g., via binding) with MHC molecules for presentation by cells, such as antigen presenting cells to specific T cells.

[001408] The term "disease involving an antigen" refers to any disease which implicates an antigen, e.g. a disease which is characterized by the presence of an antigen. The disease involving an antigen can be an infectious disease. As mentioned above, the antigen may be a disease-associated antigen, such as a viral antigen. In one embodiment, a disease involving an antigen is a disease involving cells expressing an antigen, preferably on the cell surface.

[001409] The term "infectious disease" refers to any disease which can be transmitted from individual to individual or from organism to organism, and is caused by a microbial agent (e.g. common cold). Infectious diseases are known in the art and include, for example, a viral disease, a bacterial disease, or a parasitic disease, which diseases are caused by a virus, a bacterium, and a parasite, respectively. In this regard, the infectious disease can be, for example, hepatitis, sexually transmitted diseases (e.g. chlamydia or gonorrhea), tuberculosis, HIV/acquired immune deficiency syndrome (AIDS), diphtheria, hepatitis B, hepatitis C, cholera, severe acute respiratory syndrome (SARS), the bird flu, and influenza.

[001410] Exemplary Dosing Regimens

[001411] In some embodiments, compositions and methods disclosed herein can be used in accordance with an exemplary vaccination regimen as illustrated in Figure 2.

[001412] Primary Dosing Regimens

[001413] In some embodiments, subjects are administered a primary dosing regimen. A primary dosing regimen can comprise one or more doses. For example, in some embodiments, a primary dosing regimen comprises a single dose (PD1). In some embodiments a primary dosing regimen comprises a first dose (PD1) and a second dose (PD2). In some embodiments, a primary dosing regimen comprises a first dose, a second dose, and a third dose (PD3). In some embodiments, a primary dosing regimen comprises a first dose, a second dose, a third dose, and one or more additional doses (PDn) of any one of the pharmaceutical compositions described herein.

[001414] In some embodiments, PD1 comprises administering 1 to 100 ug of RNA. In some embodiments, PD1 comprises administering 1 to 60 ug of RNA In some embodiments, PD1 comprises administering 1 to 50 ug of RNA. In some embodiments, PD1 comprises administering 1 to 30 ug of RNA. In some embodiments, PD1 comprises administering about 3 ug of RNA. In some embodiments, PD1 comprises administering about 5 ug of RNA. In some embodiments, PD1 comprises administering about 10 ug of RNA. In some embodiments, PD1 comprises administering about 15 ug of RNA. In some embodiments, PD1 comprises administering about 20 ug of RNA. In some embodiments, PD1 comprises administering about 30 ug of RNA. In some embodiments, PD1 comprises administering about 50 ug of RNA. In some embodiments, PD1 comprises administering about 60 ug of RNA.

[001415] In some embodiments, PD2 comprises administering 1 to 100 ug of RNA. In some embodiments, PD2 comprises administering 1 to 60 ug of RNA. In some embodiments, PD2 comprises administering 1 to 50 ug of RNA. In some embodiments, PD2 comprises administering 1 to 30 ug of RNA. In some embodiments, PD2 comprises administering about 3 ug. In some embodiments, PD2 comprises administering about 5 ug of RNA. In some embodiments, PD2 comprises administering about 10 ug of RNA. In some embodiments, PD2 comprises administering about 15 ug of RNA. In some embodiments, PD2 comprises administering about 20 ug RNA. In some embodiments, PD2 comprises administering about 30 ug of RNA. In some embodiments, PD2 comprises administering about 50 ug of RNA. In some embodiments, PD2 comprises administering about 60 ug of RNA. [001416] In some embodiments, PD3 comprises administering 1 to 100 ug of RNA. In some embodiments, PD3 comprises administering 1 to 60 ug of RNA. In some embodiments, PD3 comprises administering 1 to 50 ug of RNA. In some embodiments, PD3 comprises administering 1 to 30 ug of RNA. In some embodiments, PD3 comprises administering about 3 ug of RNA. In some embodiments, PD3 comprises administering about 5 ug of RNA. In some embodiments, PD3 comprises administering about 10 ug of RNA. In some embodiments, PD3 comprises administering about 15 ug of RNA. In some embodiments, PD3 comprises administering about 20 ug of RNA. In some embodiments, PD3 comprises administering about 30 ug of RNA. In some embodiments, PD3 comprises administering about 50 ug of RNA. In some embodiments, PD3 comprises administering about 60 ug of RNA.

[001417] In some embodiments, PDn comprises administering 1 to 100 ug of RNA. In some embodiments, PDn comprises administering 1 to 60 ug of RNA. In some embodiments, PDn comprises administering 1 to 50 ug of RNA. In some embodiments, PDn comprises administering 1 to 30 ug of RNA. In some embodiments, PDn comprises administering about 3 ug of RNA. In some embodiments, PDn comprises administering about 5 ug of RNA. In some embodiments, PDn comprises administering about 10 ug of RNA. In some embodiments, PDn comprises administering about 15 ug of RNA. In some embodiments, PDn comprises administering about 20 ug of RNA. In some embodiments, PDn comprises administering about 30 ug of RNA. In some embodiments, PDn comprises administering about 50 ug of RNA. In some embodiments, PDn comprises administering about 60 ug of RNA.

[001418] In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, PD1 comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant). In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more additional RNAs encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.l.5, XBB.l.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001419] In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, PD2 comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant). In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more additional RNAs encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001420] In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, PD3 comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant). In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more additional RNAs encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, or XBB.2.3.2, or BQ.l Omicron variant).

[001421] In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, PDn comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant). In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more additional RNAs encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, PDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.l.5, XBB.l.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001422] In some embodiments, PD1, PD2, PD3, and PDn can each independently comprise a plurality of (e.g., at least two) mRNA compositions described herein. In some embodiments PD1, PD2, PD3, and PDn can each independently comprise a first and a second mRNA composition. In some embodiments, at least one of a plurality of mRNA compositions comprises BNT162b2 (e.g., as described herein). In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a different SARS-CoV-2 variant. In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a Wuhan strain of SARS-CoV-2. In some embodiments, at least one of a plurarity of mRNA compositions comprises an RNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.l.5, XBB.l.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001423] In some embodiments, a plurality of mRNA compositions given in PD1, PD2, PD3, and/or PDn can each independently comprise at least two different mRNA constructs (e.g., differing in at protein-encoding sequences). For example, in some embodiments a plurality of mRNA compositions given in PD1, PD2, PD3, and/or PDn can each independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a Wuhan strain of SARS-CoV-2 and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments a plurality of mRNA compositions given in PD1, PD2, PD3, and/or PDn can each independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof derived from a Wuhan strain of SARS-CoV-2 and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some such embodiments, a variant can be an alpha variant. In some such embodiments, a variant can be a delta variant. In some such embodiments a variant can be an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001424] In some embodiments, each of a plurality of mRNA compositions given in PD1, PD2, PD3, and/or PDn can independently comprise at least two mRNAs, each encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a distinct variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, each of a plurality of mRNA compositions given in PD1, PD2, PD3, and/or PDn can independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from an alpha variant and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, each of a plurality of mRNA compositions given in PD1, PD2, PD3, and/or PDn can independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from an alpha variant and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant). In some embodiments, each of a plurality of mRNA compositions given in PD1, PD2, PD3, and/or PDn can independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a delta variant and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001425] In some embodiments, PD1, PD2, PD3, and/or PDn each comprise a plurality of mRNA compositions, wherein each mRNA composition is separately administered to a subject. For example, in some embodiments each mRNA composition is administered via intramuscular injection at different injection sites. For example, in some embodiments, a first and second mRNA composition given in PD1, PD2, PD3, and/or PDn are separately administered to different arms of a subject via intramuscular injection.

[001426] In some embodiments, PD1, PD2, PD3, and/or PDn comprise administering a plurality of RNA molecules, wherein each RNA molecule encodes a Spike protein comprising mutations from a different SARS-CoV- 2 variant, and wherein the plurality of RNA molecules are administered to the subject in a single formulation. In some embodiments, the single formulation comprises an RNA encoding a Spike protein or an immunogenic variant thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, the single formulation comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, the single formulation comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, the single formulation comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001427] In some embodiments, the length of time between PD1 and PD2 (PI1) is at least about 1 week, at least about 2 weeks, at least about 3 weeks, or at least about 4 weeks. In some embodiments, PI1 is about 1 week to about 12 weeks. In some embodiments, PI1 is about 1 week to about 10 weeks. In some embodiments, PI1 is about 2 weeks to about 10 weeks. In some embodiments, PI1 is about 2 weeks to about 8 weeks. In some embodiments, PH is about 3 weeks to about 8 weeks. In some embodiments, PI1 is about 4 weeks to about 8 weeks. In some embodiments, PH is about 6 weeks to about 8 weeks. In some embodiments PH is about 3 to about 4 weeks. In some embodiments, PH is about 1 week. In some embodiments, PH is about 2 weeks. In some embodiments, PI1 is about 3 weeks. In some embodiments, PI1 is about 4 weeks. In some embodiments, PI1 is about 5 weeks. In some embodiments, PI1 is about 6 weeks. In some embodiments, PI1 is about 7 weeks. In some embodiments, PI1 is about 8 weeks. In some embodiments, PH is about 9 weeks. In some embodiments, PH is about 10 weeks. In some embodiments, PH is about 11 weeks. In some embodiments, PI1 is about 12 weeks.

[001428] In some embodiments, the length of time between PD2 and PD3 (PI2) is at least about 1 week, at least about 2 weeks, or at least about 3 weeks. In some embodiments, PI2 is about 1 week to about 12 weeks. In some embodiments, PI2 is about 1 week to about 10 weeks. In some embodiments, PI2 is about 2 weeks to about 10 weeks. In some embodiments, PI2 is about 2 weeks to about 8 weeks. In some embodiments, PI2 is about 3 weeks to about 8 weeks. In some embodiments, PI2 is about 4 weeks to about 8 weeks. In some embodiments, PI2 is about 6 weeks to about 8 weeks. In some embodiments PI2 is about 3 to about 4 weeks. In some embodiments, PI2 is about 1 week. In some embodiments, PI2 is about 2 weeks. In some embodiments, PI2 is about 3 weeks. In some embodiments, PI2 is about 4 weeks. In some embodiments, PI2 is about 5 weeks. In some embodiments, PI2 is about 6 weeks. In some embodiments, PI2 is about 7 weeks. In some embodiments, PI2 is about 8 weeks. In some embodiments, PI2 is about 9 weeks. In some embodiments, PI2 is about 10 weeks. In some embodiments, PI2 is about 11 weeks. In some embodiments, PI2 is about 12 weeks.

[001429] In some embodiments, the length of time between PD3 and a subsequent dose that is part of the Primary Dosing Regimen, or between doses for any dose beyond PD3 (Pin) is each separately and independently selected from: about 1 week or more, about 2 weeks or more, or about 3 weeks or more. In some embodiments, Pin is about 1 week to about 12 weeks. In some embodiments, Pin is about 1 week to about 10 weeks. In some embodiments, Pin is about 2 weeks to about 10 weeks. In some embodiments, Pin is about 2 weeks to about 8 weeks. In some embodiments, Pin is about 3 weeks to about 8 weeks. In some embodiments, Pin is about 4 weeks to about 8 weeks. In some embodiments, Pin is about 6 weeks to about 8 weeks. In some embodiments Pin is about 3 to about 4 weeks. In some embodiments, PI2 is about 1 week. In some embodiments, Pin is about 2 weeks. In some embodiments, Pin is about 3 weeks. In some embodiments, Pin is about 4 weeks. In some embodiments, Pin is about 5 weeks. In some embodiments, PInis about 6 weeks. In some embodiments, Pin is about 7 weeks. In some embodiments, PInis about 8 weeks. In some embodiments, Pin is about 9 weeks. In some embodiments, Pin is about 10 weeks. In some embodiments, Pin is about 11 weeks. In some embodiments, Pin is about 12 weeks.

[001430] In some embodiments, one or more compositions administered in PD1 are formulated in a Tris buffer. In some embodiments, one or more compositions administered in PD2 are formulated in a Tris buffer. In some embodiments, one or more compositions administering in PD3 are formulated in a Tris buffer. In some embodiments, one or more compositions adminsitered in PDn are formulated in a Tris buffer. [001431] In some embodiments, the primary dosing regimen comprises administering two or more mRNA compositions described herein, and at least two of the mRNA compositions have different formulations. In some embodiments, the primary dosing regimen comprises PD1 and PD2, where PD1 comprises administering an mRNA formulated in a Tris buffer and PD2 comprises administering an mRNA formulated in a PBS buffer. In some embodiments, the primary dosing regimen comprises PD1 and PD2, where PD1 comprises administering an mRNA formulated in a PBS buffer and PD2 comprises administering an mRNA formulated in a Tris buffer.

[001432] In some embodiments, one or more mRNA compositions given in PD1, PD2, PD3, and/or PDn can be administered in combination with another vaccine. In some embodiments, another vaccine is for a disease that is not COVID-19. In some embodiments, the disease is one that increases deleterious effects of SARS-CoV-2 when a subject is coinfected with the disease and SARS-CoV-2. In some embodiments, the disease is one that increases the transmission rate of SARS-CoV-2 when a subject is coinfected with the disease and SARS-CoV-2. In some embodiments, another vaccine is a different commercially available vaccine. In some embodiments, the different commercially available vaccine is an RNA vaccine. In some embodiments, the different commercially available vaccine is a polypeptide-based vaccine. In some embodiments, another vaccine (e.g., as described herein) and one or more mRNA compositions given in PD1, PD2, PD3, and/or PDn are separately administered, for example, in some embodiments via intramuscular injection, at different injection sites. For example, in some embodiments, an influenza vaccine and one or more SARS-CoV-2 mRNA compositions described herein given in PD1, PD2, PD3, and/or PDn are separately administered to different arms of a subject via intramuscular injection. [001433] Booster Dosing Regimens

[001434] In some embodiments, methods of vaccination disclosed herein comprise one or more Booster Dosing Regimens. The Booster Dosing Regimens disclosed herein comprise one or more doses. In some embodiments, a Booster Dosing Regimen is administered to patients who have been administered a Primary Dosing Regimen (e.g., as described herein). In some embodiments a Booster Dosing Regimen is administered to patients who have not received a pharmaceutical composition disclosed herein. In some embodiments a Booster Dosing Regimen is administered to patients who have been previously vaccinated with a COVID-19 vaccine that is different from the vaccine administered in a Primary Dosing Regimen.

[001435] In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, or at least 12 months or longer. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is about 1 month. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is at least about 2 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is at least about 3 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is at least about 4 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is at least about 5 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is at least about 6 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is from about 1 month to about 48 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is from about 1 month to about 36 months. In some embodiments, the length of time between the primary dosing regimen and the Booster Dosing Regimen is from about 1 month to about 24 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is from about 2 months to about 24 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is from about 3 months to about 24 months. In some embodiments, the length of time between the primary dosing regimen and the Booster Dosing Regimen is from about 3 months to about 18 months. In some embodiments, the length of time between the primary dosing regimen and the Booster Dosing Regimen is from about 3 months to about 12 months. In some embodiments, the length of time between the primary dosing regimen and the Booster Dosing Regimen is from about 6 months to about 12 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is from about 3 months to about 9 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is from about 5 months to about 7 months. In some embodiments, the length of time between the Primary Dosing Regimen and the Booster Dosing Regimen is about 6 months. [001436] In some embodiments, subjects are administered a Booster Dosing Regimen. A Booster dosing regimen can comprise one or more doses. For example, in some embodiments, a Booster Dosing Regimen comprises a single dose (BD1). In some embodiments a Booster Dosing Regimen comprises a first dose (BD1) and a second dose (BD2). In some embodiments, a Booster Dosing Regimen comprises a first dose, a second dose, and a third dose (BD3). In some embodiments, a Booster Dosing Regimen comprises a first dose, a second dose, a third dose, and one or more additional doses (BDn) of any one of the pharmaceutical compositions described herein.

[001437] In some embodiments, BD1 comprises administering 1 to 100 ug of RNA. In some embodiments, BD1 comprises administering 1 to 60 ug of RNA. In some embodiments, BD1 comprises administering 1 to 50 ug of RNA. In some embodiments, BD1 comprises administering 1 to 30 ug of RNA. In some embodiments, BD1 comprises administering about 3 ug of RNA. In some embodiments, BD1 comprises administering about 5 ug of RNA. In some embodiments, BD1 comprises administering about 10 ug of RNA. In some embodiments, BD1 comprises administering about 15 ug of RNA. In some embodiments, BD1 comprises administering about 20 ug of RNA. In some embodiments, BD1 comprises administering about 30 ug of RNA. In some embodiments, BD1 comprises administering about 50 ug of RNA. In some embodiments, BD1 comprises administering about 60 ug of RNA.

[001438] In some embodiments, BD2 comprises administering 1 to 100 ug of RNA. In some embodiments, BD2 comprises administering 1 to 60 ug of RNA. In some embodiments, BD2 comprises administering 1 to 50 ug of RNA. In some embodiments, BD2 comprises administering 1 to 30 ug of RNA. In some embodiments, BD2 comprises administering about 3 ug. In some embodiments, BD2 comprises administering about 5 ug of RNA. In some embodiments, BD2 comprises administering about 10 ug of RNA. In some embodiments, BD2 comprises administering about 15 ug of RNA. In some embodiments, BD2 comprises administering about 20 ug RNA. In some embodiments, BD2 comprises administering about 30 ug of RNA. In some embodiments, BD2 comprises administering about 50 ug of RNA. In some embodiments, BD2 comprises administering about 60 ug of RNA. [001439] In some embodiments, BD3 comprises administering 1 to 100 ug of RNA. In some embodiments, BD3 comprises administering 1 to 60 ug of RNA. In some embodiments, BD3 comprises administering 1 to 50 ug of RNA. In some embodiments, BD3 comprises administering 1 to 30 ug of RNA. In some embodiments, BD3 comprises administering about 3 ug of RNA. In some embodiments, BD3 comprises administering about 5 ug of RNA. In some embodiments, BD3 comprises administering about 10 ug of RNA. In some embodiments, BD3 comprises administering about 15 ug of RNA. In some embodiments, BD3 comprises administering about 20 ug of RNA. In some embodiments, BD3 comprises administering about 30 ug of RNA. In some embodiments, BD3 comprises administering about 50 ug of RNA. In some embodiments, BD3 comprises administering about 60 ug of RNA. [001440] In some embodiments, BDn comprises administering 1 to 100 ug of RNA. In some embodiments, BDn comprises administering 1 to 60 ug of RNA. In some embodiments, BDn comprises administering 1 to 50 ug of RNA. In some embodiments, BDn comprises administering 1 to 30 ug of RNA. In some embodiments, BDn comprises administering about 3 ug of RNA. In some embodiments, BDn comprises administering about 5 ug of RNA. In some embodiments, BDn comprises administering about 10 ug of RNA. In some embodiments, BDn comprises administering about 15 ug of RNA. In some embodiments, BDn comprises administering about 20 ug of RNA. In some embodiments, BDn comprises administering about 30 ug of RNA. In some embodiments, BDn comprises administering about 60 ug of RNA. In some embodiments, BDn comprises administering about 50 ug of RNA.

[001441] In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, BD1 comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, or BQ.l Omicron variant).

[001442] In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BD1 comprises an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BD1 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, or BQ.l Omicron variant).

[001443] In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, BD2 comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, or BQ.l Omicron variant). In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BD2 comprises an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BD2 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.l.5, XBB.l.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001444] In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, BD3 comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.l.5, XBB.l.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001445] In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BD3 comprises an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BD3 comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.l.5, XBB.l.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001446] In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain. In some embodiments, BDn comprises an RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variance. g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001447] In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and one or more RNA encoding a Spike protein or an immunogenic fragment thereof from a SARS-CoV-2 strain that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, BDn comprises an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS- CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from a beta variant. In some embodiments, BDn comprises an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof from the Wuhan strain and an RNA encoding a SARS-CoV-2 Spike protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001448] In some embodiments, BD1, BD2, BD3, and BDn can each independently comprise a plurality of (e.g., at least two) mRNA compositions described herein. In some embodiments BD1, BD2, BD3, and BDn can each independently comprise a first and a second mRNA composition. In some embodiments, BD1, BD2, BD3, and BDn can each independently comprise a plurality of (e.g., at least two) mRNA compositions, wherein , at least one of the plurality of mRNA compositions comprises BNT162b2 (e.g., as described herein). In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a different SARS-CoV-2 variant (e.g., a variant that is prevalent or rapidly spreading in a relevant jurisdiction, e.g., a variant disclosed herein). In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a Wuhan strain of SARS-CoV-2. In some embodiments, at least one of a plurality of mRNA compositions comprises an RNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an alpha variant. In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments, at least one of a plurality of mRNA compositions comprises an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant). [001449] In some embodiments, a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn can each independently comprise at least two different mRNA constructs (e.g., mRNA constructs having differing protein-encoding sequences). For example, in some embodiments a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn can each independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a Wuhan strain of SARS-CoV-2 and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn can each independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof derived from a Wuhan strain of SARS-CoV-2 and an mRNA encoding a SARS- CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some such embodiments, a variant can be an alpha variant. In some such embodiments, a variant can be a delta variant. In some such embodiments a variant can be an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001450] In some embodiments, a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn can each independently comprise at least two mRNAs each encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a distinct variant that is prevalent and/or spreading rapidly in a relevant jurisdiction. In some embodiments a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn can each independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from an alpha variant and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from a delta variant. In some embodiments a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn can each independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from an alpha variant and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant). In some embodiments a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn can each independently comprise an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof from a delta variant and an mRNA encoding a SARS-CoV-2 S protein or an immunogenic fragment thereof comprising one or more mutations from an Omicron variant (e.g., a BA.4/5, BA.l, BA.2, XBB, XBB.l, XBB.1.5, XBB.1.16, XBB.2.3, XBB.2.3.2, or BQ.l Omicron variant).

[001451] In some embodiments, a plurality of mRNA compositions given in BD1, BD2, BD3, and/or BDn are separately administered to a subject, for example, in some embodiments via intramuscular injection, at different injection sites. For example, in some embodiments, a first and second mRNA composition given in BD1, BD2, BD3, and/or BDn are separately administered to different arms of a subject via intramuscular injection.

[001452] In some embodiments, the length of time between BD1 and BD2 (BI1) is at least about 1 week, at least about 2 weeks, at least about 3 weeks, or at least about 4 weeks. In some embodiments, BI1 is about 1 week to about 12 weeks. In some embodiments, BI1 is about 1 week to about 10 weeks. In some embodiments, BI1 is about 2 weeks to about 10 weeks. In some embodiments, BI1 is about 2 weeks to about 8 weeks. In some embodiments, BI1 is about 3 weeks to about 8 weeks. In some embodiments, BI1 is about 4 weeks to about 8 weeks. In some embodiments, BU is about 6 weeks to about 8 weeks. In some embodiments BI1 is about 3 to about 4 weeks. In some embodiments, BI1 is about 1 week. In some embodiments, BI1 is about 2 weeks. In some embodiments, BI1 is about 3 weeks. In some embodiments, BI1 is about 4 weeks. In some embodiments, BI1 is about 5 weeks. In some embodiments, BI1 is about 6 weeks. In some embodiments, BI1 is about 7 weeks. In some embodiments, BI1 is about 8 weeks. In some embodiments, BI1 is about 9 weeks. In some embodiments, BI1 is about 10 weeks.

[001453] In some embodiments, the length of time between BD2 and BD3 (BI2) is at least about 1 week, at least about 2 weeks, or at least about 3 weeks. In some embodiments, BI2 is about 1 week to about 12 weeks. In some embodiments, BI2 is about 1 week to about 10 weeks. In some embodiments, BI2 is about 2 weeks to about 10 weeks. In some embodiments, BI2 is about 2 weeks to about 8 weeks. In some embodiments, BI2 is about 3 weeks to about 8 weeks. In some embodiments, BI2 is about 4 weeks to about 8 weeks. In some embodiments, BI2 is about 6 weeks to about 8 weeks. In some embodiments BI2 is about 3 to about 4 weeks. In some embodiments, BI2 is about 1 week. In some embodiments, BI2 is about 2 weeks. In some embodiments, BI2 is about 3 weeks. In some embodiments, BI2 is about 4 weeks. In some embodiments, BI2 is about 5 weeks. In some embodiments, BI2 is about 6 weeks. In some embodiments, BI2 is about 7 weeks. In some embodiments, BI2 is about 8 weeks. In some embodiments, BI2 is about 9 weeks. In some embodiments, BI2 is about 10 weeks.

[001454] In some embodiments, the length of time between BD3 and a subsequent dose that is part of the Booster Dosing Regimen, or between doses for any dose beyond BD3 (Bln) is each separately and independently selected from: about 1 week or more, about 2 weeks or more, or about 3 weeks or more. In some embodiments, Bln is about 1 week to about 12 weeks. In some embodiments, Bln is about 1 week to about 10 weeks. In some embodiments, Bln is about 2 weeks to about 10 weeks. In some embodiments, Bln is about 2 weeks to about 8 weeks. In some embodiments, Bln is about 3 weeks to about 8 weeks. In some embodiments, Bln is about 4 weeks to about 8 weeks. In some embodiments, Bln is about 6 weeks to about 8 weeks. In some embodiments Bln is about 3 to about 4 weeks. In some embodiments, Bln is about 1 week. In some embodiments, Bln is about 2 weeks. In some embodiments, Bln is about 3 weeks. In some embodiments, Bln is about 4 weeks. In some embodiments, Bln is about 5 weeks. In some embodiments, Bln is about 6 weeks. In some embodiments, Bln is about 7 weeks. In some embodiments, Bln is about 8 weeks. In some embodiments, Bln is about 9 weeks. In some embodiments, Bln is about 10 weeks.

[001455] In some embodiments, one or more compositions adminstered in BD1 are formulated in a Tris buffer. In some embodiments, one or more compositions administered in BD2 are formulated in a Tris buffer. In some embodiments, one or more compositions administering in BD3 are formulated in a Tris buffer. In some embodiments, one or more compositions adminsitered in BD3 are formulated in a Tris buffer.

[001456] In some embodiments, the Booster dosing regimen comprises administering two or more mRNA compositions described herein, and at least two of the mRNA compositions have different formulations. In some embodiments, the Booster dosing regimen comprises BD1 and BD2, where BD1 comprises administering an mRNA formulated in a Tris buffer and BD2 comprises administering an mRNA formulated in a PBS buffer. In some embodiments, the Booster dosing regimen comprises BD1 and BD2, where BD1 comprises administering an mRNA formulated in a PBS buffer and BD2 comprises administering an mRNA formulated in a Tris buffer. [001457] In some embodiments, one or more mRNA compositions given in BD1, BD2, BD3, and/or BDn can be administered in combination with another vaccine. In some embodiments, another vaccine is for a disease that is not COVID-19. In some embodiments, the disease is one that increases deleterious effects of SARS-CoV-2 when a subject is coinfected with the disease and SARS-CoV-2. In some embodiments, the disease is one that increases the transmission rate of SARS-CoV-2 when a subject is coinfected with the disease and SARS-CoV-2. In some embodiments, another vaccine is a different commercially available vaccine. In some embodiments, the different commercially available vaccine is an RNA vaccine. In some embodiments, the different commercially available vaccine is a polypeptide-based vaccine. In some embodiments, another vaccine (e.g., as described herein) and one or more mRNA compositions given in BD1, BD2, BD3, and/or BDn are separately administered, for example, in some embodiments via intramuscular injection, at different injection sites. For example, in some embodiments, an influenza vaccine and one or more SARS-CoV-2 mRNA compositions described herein given in BD1, BD2, BD3, and/or BDn are separately administered to different arms of a subject via intramuscular injection. [001458] Additional Booster Regimens

[001459] In some embodiments, methods of vaccination disclosed herein comprise administering more than one Booster Dosing Regimen. In some embodiments, more than one Booster Dosing Regimen may need to be administered to increase neutralizing antibody response. In some embodiments, more than one booster dosing regimen may be needed to counteract a SARS-CoV-2 strain that has been shown to have a high likelihood of evading immune response elicited by vaccines that a patient has previously received. In some embodiments, an additional Booster Dosing Regimen is administered to a patient who has been determined to produce low concentrations of neutralizing antibodies. In some embodiments, an additional booster dosing regimen is administered to a patient who has been determined to have a high likelihood of being susceptible to SARS-CoV-2 infection, despite previous vaccination (e.g., an immunocompromised patient, a cancer patient, and/or an organ transplant patient).

[001460] The description provided above for the first Booster Dosing Regimen also describes the one or more additional Booster Dosing Regimens. The interval of time between the first Booster Dosing Regimen and a second Booster Dosing Regimen, or between subsequent Booster Dosing Regimens can be any of the acceptable intervals of time described above between the Primary Dosing Regimen and the First Booster Dosing Regimen. [001461] In some embodiments, a dosing regimen comprises a primary regimen and a booster regimen, wherein at least one dose given in the primary regimen and/or the booster regimen comprises a composition comprising an RNA that encodes a S protein or immunogenic fragment thereof from a variant that is prevalent or is spreading rapidly in a relevant jurisdiction (e.g., Omicron variant as described herein). For example, in some embodiments, a primary regimen comprises at least 2 doses of BNT162b2 (e.g., encoding a Wuhan strain), for example, given at least 3 weeks apart, and a booster regimen comprises at least 1 dose of a composition comprising RNA that encodes a S protein or immunogenic fragment thereof from a variant that is prevalent or is spreading rapidly in a relevant jurisdiction (e.g., Omicron variant as described herein). In some such embodiments, such a dose of a booster regimen may further comprise an RNA that encodes a S protein or immunogenic fragment thereof from a Wuhan strain, which can be administered with an RNA that encodes a S protein or immunogenic fragment thereof from a variant that is prevalent or is spreading rapidly in a relevant jurisdiction (e.g., Omicron variant as described herein), as a single mixture, or as two separate compositions, for example, in 1:1 weight ratio. In some embodiments, a booster regimen can also comprise at least 1 dose of BNT162b2, which can be administered as a first booster dose or a subsequent booster dose.

[001462] In some embodiments, an RNA composition described herein is given as a booster at a dose that is higher than the doses given during a primary regimen (primary doses) and/or the dose given for a first booster, if any. For example, in some embodiments, such a dose may be 60 ug; or in some embodiments such a dose may be higher than 30 ug and lower than 60 ug (e.g., 55 ug, 50 ug, or lower). In some embodiments, an RNA composition described herein is given as a booster at least 3-12 months or 4-12 months, or 5-12 months, or 6-12 months after the last dose (e.g., the last dose of a primary regimen or a first dose of a booster regimen). In some embodiments, the primary doses and/or the first booster dose (if any) may comprise BNT162b2, for example at 30 ug per dose.

[001463] In some embodiments, an RNA composition described herein comprises an RNA encoding a polypeptide as set forth in SEQ ID NO: 158 or an immunogenic fragment thereof, or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 158). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 159 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 159). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 161 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 161).

[001464] In some embodiments, an RNA composition comprises an RNA comprising (a) a nucleotide sequence of SEQ ID NO: 161 or a sequence that is at least 70% identical to SEQ ID NO: 161 (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or higher, identity to SEQ ID NO: 108), and/or (b) a nucleotide sequence that encodes a SARS-CoV-2 S protein having an amino acid sequence of SEQ ID NO: 158, or an amino acid sequence that is at least 70% identical to SEQ ID NO: 158 (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or higher, identity to SEQ ID NO: 158), and (c) wherein the SARS-CoV-2 S protein optionally comprises one or more mutations that stabilize a prefusion confirmation (e.g., proline mutations at positions 982 and 983 of SEQ ID NO: 158). In some embodiments, such a composition comprises one or more additional RNAs, each encoding an S protein of a non-XBB.1.5 SARS-CoV strain or variant (e.g., a Wuhan strain, an Omicron BA.4/5 variant, and/or an Omicron BA.2.75.2 variant (e.g., such RNAs described herein)).

[001465] In some embodiments, an RNA composition described herein (e.g., a monovalent, bivalent, trivalent, or quadrivalent composition) comprises an RNA encoding a polypeptide as set forth in SEQ ID NO: 163 or an immunogenic fragment thereof, or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 163). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 164 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 164). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 166 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 166).

[001466] In some embodiments, an RNA composition described herein (e.g., a monovalent, bivalent, trivalent, or quadrivalent composition) comprises an RNA encoding a polypeptide as set forth in SEQ ID NO: 168 or an immunogenic fragment thereof, or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 168). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 169 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 169). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 171 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 171).

[001467] In some embodiments, an RNA composition described herein (e.g., a monovalent, bivalent, trivalent, or quadrivalent composition) comprises an RNA encoding a polypeptide as set forth in SEQ ID NO: 173 or an immunogenic fragment thereof, or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 173). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 174 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 174). In some embodiments, an RNA composition comprises an RNA that includes the sequence of SEQ ID NO: 176 or a variant thereof (e.g., having at least 70% or more, including, e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or higher, identity to SEQ ID NO: 176).

[001468] In some embodiments, the formulations disclosed herein can be used to carry out any of the dosing regimens described in Table C (below).

Table C: Exemplary Dosing Regimens:

1N/A refers to no dose necessary.

[001469] In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a first dose of a primary regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a second dose of a primary regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a first dose and a second dose of a primary regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a first dose of a booster regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a second dose of a booster regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a first dose and a second dose of a booster regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a first dose and a second dose of a primary regimen and also in at least one dose of a booster regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in at least one dose (including, e.g., at least two doses) of a booster regimen and BNT162b2 is given in a primary regimen. In some embodiments of certain exemplary dosing regimens as described in Table C above, an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) is given in a second dose of a booster regimen and BNT162b2 is given in a primary regimen and in a first dose of a booster regimen.

[001470] In some embodiments, such an RNA composition described herein (e.g., comprising RNA encoding a variant described herein) can further comprise RNA encoding a S protein or an immunogenic fragment thereof of a different strain (e.g., a Wuhan strain). By way of example, in some embodiments, a second dose of a booster regimen of Regimens #9-11 as described in Table C above can comprise an RNA composition described herein (e.g., comprising RNA encoding a variant described herein such as Omicron, for example, in one embodiment RNA as described in this Example) and a BNT162b2 construct, for example, in 1: 1 weight ratio.

[001471] In some embodiments of Regimen #6 as described in Table C above, a first dose and a second dose of a primary regimen and a first dose and a second dose of a booster regimen each comprise an RNA composition described herein (e.g., comprising RNA encoding a variant described herein such as Omicron, for example, in one embodiment RNA as described in this Example). In some such embodiments, a second dose of a booster regimen may not be necessary.

[001472] In some embodiments of Regimen #6 as described in Table C above, a first dose and a second dose of a primary regimen and a first dose and a second dose of a booster regimen each comprise an RNA composition described herein (e.g., comprising RNA encoding a variant described herein such as Omicron, for example, in one embodiment RNA as described in this Example). In some such embodiments, a second dose of a booster regimen may not be necessary.

[001473] In some embodiments of Regimen #6 as described in Table C above, a first dose and a second dose of a primary regimen each comprise a BNT162b2 construct, and a first dose and a second dose of a booster regimen each comprise an RNA composition described herein (e.g., comprising RNA encoding a variant described herein such as Omicron, for example, in one embodiment RNA as described in this Example). In some such embodiments, a second dose of a booster regimen may not be necessary.

[001474] In some embodiments of Regimen #6 as described in Table C above, a first dose and a second dose of a primary regimen and a first dose of a booster regimen each comprise a BNT162b2 construct, and a second dose of a booster regimen comprises an RNA composition described herein (e.g., comprising RNA encoding a variant described herein such as Omicron, for example, in one embodiment RNA as described in this Example).

[001475] Citation of documents and studies referenced herein is not intended as an admission that any of the foregoing is pertinent prior art. All statements as to the contents of these documents are based on the information available to the applicants and do not constitute any admission as to the correctness of the contents of these documents.

Enumerated Embodiments

1. An RNA comprising a nucleotide sequence encoding a polypeptide comprising an S2 domain, or a fragment thereoof.

2. The RNA of embodiment 1, wherein the polypeptide comprises amino acid 686-1213 of SEQ ID NO: 1, 686-1211 of SEQ ID NO: 1, amino acids 687-1206 of SEQ ID NO: 1, or amino acids 687-1211 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant, optionally wherein the S2 domain compries one or more mutations that stabilize the S2 domain (e.g., stabilize the prefusion conformation of the S2 domain).

3. The RNA of embodiment 1 or 2, wherein the S2 domain comprises:

(a) an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIKWP, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto;

(b) an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEP QIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto;

(c) an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

(d) an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCG KGYH LMSFPQSAPHG VVFLH YTYVPAQEKN FTTAPAICH DGKAH FPREGVFVSNGTHWFVTQRN FYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKY, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

4. The RNA of any one of embodiments 1-3, wherein the S2 domain or the fragment thereof comprises a stem helix and/or a fusion peptide of an S2 domain.

5. The RNA of embodiment 4, wherein the fusion peptide comprises a sequence of PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto, and the stem helix comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

6. The RNA of any one of embodiments 1-5, wherein the S2 domain comprises one or more stabilizing mutations.

7. The RNA of embodiment 6, wherein the one or more stabilizing mutations comprise one or more mutations that can stabilize the prefusion confirmation of an S protein.

8. The RNA of embodiment 6 or 7, wherein the one or more stabilizing mutations include one or more Pro substitutions.

9. The RNA of any one of embodiments 1-8, wherein the S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1, or corresponding mutation(s) in an S2 domain of an S protein of a SARS-CoV- 2 variant:

(a) K986P and V987P;

(b) A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P;

(c) F817P, A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P; or

(d) any combination of (a)-(c).

10. The RNA of any one of embodiments 1-9, wherein the S2 domain comprises one or more mutations that can result in the formation of a disulfide bond. 11. The RNA of any one of embodiments 1-10, wherein the S2 domain comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S2 domain of a SARS-CoV-2 variant:

(a) V707C and T883C;

(b) I770C and A1015C;

(c) V826C and A1015C;

(d) V826C and L948C;

(e) F970C and G999C;

(f) S735C and T859C; or

(g) any combination of (a)-(e).

12. The RNA of embodiment 11, wherein the S2 domain comprises one or more of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S protein of a SARS-CoV-2 variant:

(a) V707C, T883C, F970C, and G999C;

(b) S735C, T859C, I770C, and A1015C;

(c) S735C, T859C, V826C, and L948C;

(d) I770C, A1015C, V826C, and L948C;

(e) S735C, I770C, A1015C, V826C, and L948C; or

(f) any combination of (a)-(e).

13. The RNA of any one of embodiments 1-12, wherein the S2 domain comprises one or more Pro substitions and one or more mutations that can lead to the formation of a disulfide bond.

14. The RNA of any one of embodiments 1-13, wherein the S2 domain comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresonding combination of mutations of an S2 domain of a SARS-CoV-2 variant:

(a) A892P, A899P, 941, K986P, V987P, G999C, and I770C;

(b) A892P, A899P, A942P, V987P, V707C, T883C, optionally wherein the S2 domain compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(c) A892P, A899P, A942P, V987P, V707C, T883C, F970C, G999C, optionally wherein the S2 domain compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1.

15. The RNA of any one of embodiments 1-14, wherein the S2 domain comprises one or more mutations that can prevent or result in the reduction of cleavage at the S2' cleavage site.

16. The RNA of any one of embodiments 1-15, wherein the S2 domain comprises one or more mutations that can remove the S2' protease cleavage site.

17. The RNA of any one of embodiments 1-16, wherein the S2 domain comprises one or more mutations at positions corresponding to amino acids 814 and/or 815 of SEQ ID NO: 1, optionally wherein the one or more mutations are a Gly, Ser, or Ala substition (e.g., a Gly substition).

18. The RNA of embodiment 17, wherein the S2 domain comprises Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1.

19. The RNA of any one of embodiments 1-18, wherein the S2 domain comprises one or more Pro substitutions that can stabilize the S2 domain and one or more mutations that disrupt the S2' protease cleavage site. 20. The RNA of any one of claism 1-19, wherein the S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1: A892P, A899P, A942P, K986P, V987P, or any combination thereof, or corresponding mutations in a SARS-Cov-2 variant, and a Gly substituion at positions 814 and/or 815 of SEQ ID NO: 1.

21. The RNA of any one of embodiments 1-20, wherein the S2 domain comprises one or more substitutions of a hydrophillic amino acid for a hydrophobic amino acid, wherein the one or more hydrophobic amino acids are at positions that are solvent explosed in the S2 domain.

22. The RNA of embodiment 21, wherein the S2 domain comprises a substitution of a hydrophillic amino acid at one or more positions corresponding to amino acid 855, 861, 864, 976, or 984 of SEQ ID NO: 1, or any combination thereof.

23. The RNA of any one of embodiments 1-22, wherein the S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1 F855S, L861E, L864D, V976D, and L984Q, or any combination thereof, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

24. The RNA of any one of embodiments 1-23, wherein the S2 domain comprises an amino acid substitution at one or more of the amino acids at positions 901, 1020, 1058, or any combination thereof relative to SEQ ID NO: 1, or corresponding substitutions in an S2 domain of a SARS-CoV-2 variant.

25. The RNA of any one of embodiments 1-24, wherein the construct comprises one or more of the following mutations relative to SEQ ID NO: 1: Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

26. The RNA of any one of embodiments 1-25, wherein the S2 domain comprises:

(a) one or more of the following mutations: S375C, T859C, Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1, Pro substitutions at positions corresponding to amino acids K986P and/or V987P of SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(b) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, and Pro substiutions at positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1, wherein mutations are shown relative to SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(c) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1; or

(d) any combination of (a)-(c).

27. The RNA of any one of embodiments 1-26, wherein the S2 domain comprises one or more subsitions of a hydrophobic residue for a hydrophillic residue at one or more positions that are solvent buried in the context of the full length S protein, but which are solvent exposed in the absense of the SI domain.

28. The RNA of embodiment 27, wehrein the one or more hydrophic residues include F855S, L861E, L864D, V976D, and L984Q, where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant. 29. The RNA of any one of embodiments 1-28, wherein the S2 domain comprises one or more of the following mutations: L861E, L864D, V976D, and L984Q, a Pro substitution at one or more positions corresponding to amino acids F817P, A892P, A899P, A942P, or combinations thereof of SEQ ID NO: 1, optionally in combination with a Pro substitution at one or both positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1; or where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

30. The RNA of any one of embodiments 1-29, wherein the polypeptide comprises a multimerization domain, optionally wherein the multimerization domain is a T4 fibritin domain.

31. The RNA of embodiment 30, wherein the multimerization domain is at the C-terminus of the polypeptide.

32. The RNA of any one of embodiments 1-31, wherein the polypeptide does not comprise a transmembrane domain.

33. The RNA of any one of embodiments 1-32, wherein the polypeptide comprises a transmembrane domain, optionally where the transmembrane domain is a SARS-CoV-2 transmembrane domain (e.g., a transmembrane domain comprising an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCC, or a variant thereof, including e.g., an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC, or a variant thereof).

34. The RNA of any one of embodiments 1-33, where the polypeptide comprises a multimerization domain, and wherein the polypeptide does not comprise a transmembrane domain.

35. The RNA of any one of embodiments 1-34, wherein the polypeptide comprises a multimerization domain and a transmembrane domain, optionally wherein the multimerization domain is C-terminal to the S2 domain and the transmembrane domain is C-terminal to the trimerization domain.

36. The RNA of embodiment 35, wherein the multimerization domain is a trimerization domain (e.g., a fibritin domain, including, e.g., a peptide having an amino acid sequence of GYIPEAPRDGQAYVRKDGEWVLLSTFL, or a variant thereof) and/or wherein the tramsmembrane domain is a transmembrane domain of a SARS-CoV-2 S protein (e.g., a transmembrane domain comprising an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCC, or a variant thereof, including e.g., an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC, or a variant thereof).

37. The RNA of any one of embodiments 1-36, wherein the polypeptide comprises a secretory signal peptide (e.g., a secretory signal peptide of a viral protein), optionally wherein the secretory signal peptide is at the N- terminus of the polypeptide.

38. The RNA of embodiment 37, wherein the secretory signal peptide is a secretory signal peptide of a SARS-CoV-2 S protein (e.g., wherein the secretory signal peptide comprises amino acids 1-19 of SEQ ID NO: 1, or a an amino acid sequence of a correseponding region of an S protein of a SARS-CoV-2 variant).

39. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 178.

40. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 179. 41. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 180.

42. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 181.

43. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 182.

44. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 183.

45. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 184.

46. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 185.

47. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 186.

48. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 187.

49. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 192.

50. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 193.

51. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 194.

52. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 195.

53. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 196. 54. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 197.

55. The RNA of any one of embodiments 1-38, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO: 178, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 198.

56. The RNA of any of the preceding embodiments, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 446 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 446; (ii) the nucleotide sequence of SEQ ID NO: 447 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 447; and/or (Hi) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 183, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 183.

57. The RNA of any of the preceding embodiments, wherein the RNA comprises (i) the nucleotide sequence Of SEQ ID NO: 448 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 448; (ii) the nucleotide sequence of SEQ ID NO: 449 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 449; and/or (Hi) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 184, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 184.

58. The RNA of any of the preceding embodiments, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 450 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 450; (ii) the nucleotide sequence of SEQ ID NO: 451 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 451; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 185, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 185.

59. The RNA of any of the preceding embodiments, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 452 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 452; (ii) the nucleotide sequence of SEQ ID NO: 453 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 453; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 442, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 442.

60. The RNA of any of the preceding embodiments, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 455 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 455; (ii) the nucleotide sequence of SEQ ID NO: 456 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 456; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 443, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 443. 61. The RNA of any of the preceding embodiments, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 457 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 457; (ii) the nucleotide sequence of SEQ ID NO: 458 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 458; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 195, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 195.

62. The RNA of any of the preceding embodiments, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 459 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 459; (ii) the nucleotide sequence of SEQ ID NO: 460 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 460; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 197, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 197.

63. An RNA comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises an S2 domain or an immunogenic fragment thereof, and a Receptor Binding Domain of a SARS-CoV-2 S protein.

64. The RNA of embodiment 63, wherein the amino acid sequence connecting the S2 domain and the RBD is not an endogenous amino acid sequence.

65. The RNA of embodiment 63 or 64, wherein the S2 domain is N-terminal or C-terminal to the RBD.

66. The RNA of any one of embodiments 63-65, wherein the polypeptide does not comprise an NTD.

67. The RNA of any one of embodiments 63-66, wherein the RBD is directly linked to the S2 domain.

68. The RNA of any one of embodiments 63-67, wherein the RBD is connected to the S2 domain via a linker sequence.

69. The RNA of embodiment 68, wherein the linker sequence is a flexible linker sequence, a helical linker sequence, or a rigid linker sequence.

70. The RNA of embodiment 68 or 69, wherein the linker sequence comprises a protease recognition site.

71. The RNA of embodiment 70, wherein the linker sequence comprises a furin recognition site (e.g., an amino acid sequence of AGNRVRRSVG, or an amino acid with 1, 2, 3, 4, or more mutations thereto).

72. The RNA of any one of embodiments 63-71, wherein the polypeptide comprises one or more multimerization domains (e.g., two or mmore multimerization domains).

73. The RNA of any one of embodiments 63-72, wherein a multimerization domain (e.g., a fibritin domain is attached to each of the S2 polyeptpide and the RBD, and the RBD and the S2 domain are connected via a linker that comprises a protease cleavage site, and the polypeptide is configured such that, upon cleavage of the furin cleavage site, a fibritin domain is attached to each of the S2 domain and the RBD.

74. The RNA of embodiment 73, wherein the polypeptide comprises a transmembrane domain (e.g., a transmembrane domain comprising EQYIKWPWYIWLGFIAGLIAIVMVTIMLCC, or a variant thereof, including, e.g., EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC), and the polypeptide is configured such that, upon cleavage, one of the RBD and the S2 domain is membrane bound and the other is soluble.

75. The RNA of embodiment 74, wherein the polypeptide is configured such that the RBD is membrane bound and the S2 domain is soluble.

76. The RNA of embodiment 74 or 75, wherein the S2 is N-terminal to the RBD. 77. The RNA of any one of embodiments 73-76, wherein the transmembrane domain is C-terminal to the RED.

78. The RNA of any one of embodiments 63-77, wherein a multimerization domain is attached to each of the S2 and the RBD, wherein each of the fibritin domains is C-terminal to the S2 and the RBD.

79. The RNA of any one of embodiments 63-778, wherein the polypeptide comprises a fibritin domain directly linked to the C-terminus of the S2 domain, a fibritin domain is directly linked to the C-terminus of the RBD, the S2 is N-terminal to the RBD, a transmembrane domain is linked to the C-terminus of the fibritin domain that is at the C-terminus of the RBD, and wherein a linker sequence is located between the fibritin domain that is attached to the C-terminus of the S2 domain, and the RBD.

80. The RNA of any one of embodiments 63-79, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

81. The RNA of any one of embodiments 63-80, wherein the polypeptide comprises amino acid 686-1213 of SEQ ID NO: 1, 686-1211 of SEQ ID NO: 1, amino acids 687-1206 of SEQ ID NO: 1, or amino acids 687-1211 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant, optionally wherein the S2 domain comprises one or more mutations that stabilize the S2 domain.

82. The RNA of any one of embodiments 63-81, wherein the S2 domain comprises:

(a) an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIKWP, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto;

(b) an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto;

(c) an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHYTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

(d) an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYH LM SFPQSAPHG WFLHVTYVPAQEKN FTTAPAICH DGKAH FPREGVFVSNGTHWFVTQRN FYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKY, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

83. The RNA of any one of embodiments 63-82, wherein the S2 domain or the fragment thereof comprises a stem helix and/or a fusion peptide of an S2 domain.

84. The RNA of embodiment 83, wherein the fusion peptide comprises a sequence of PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto, and the stem helix comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

85. The RNA of any one of embodiments 63-84, wherein the S2 domain comprises one or more stabilizing mutations.

86. The RNA of embodiment 85, wherein the one or more stabilizing mutations comprise one or more mutations that can stabilize the prefusion confirmation of an S protein.

87. The RNA of embodiment 85 or 86, wherein the one or more stabilizing mutations include one or more Pro substitutions.

88. The RNA of any one of embodiments 63-87, wherein the S2 domain domain one or more of the following mutations relative to SEQ ID NO: 1, or corresponding mutation(s) in an S2 domain of an S protein of a SARS-CoV- 2 variant:

(a) K986P and V987P;

(b) A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P;

(c) F817P, A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P; or

(d) any combination of (a)-(c).

89. The RNA of any one of embodiments 63-88, wherein the S2 domain comprises one or more mutations that can result in the formation of a disulfide bond.

90. The RNA of any one of embodiments 63-89, wherein the S2 domain comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S2 domain of a SARS-CoV-2 variant:

(a) V707C and T883C;

(b) I770C and A1015C;

(c) V826C and A1015C; (d) V826C and L948C;

(e) F970C and G999C;

(f) S735C and T859C; or

(g) any combination of (a)-(e).

91. The RNA of embodiment 90, wherein the S2 domain comprises one or more of the following combinations of mutations relative to SEQ ID NO: 1, or a corresponding combination of mutations in an S protein of a SARS-CoV- 2 variant:

(a) V707C, T883C, F970C, and G999C;

(b) S735C, T859C, I770C, and A1015C;

(c) S735C, T859C, V826C, and L948C;

(d) I770C, A1015C, V826C, and L948C;

(e) S735C, I770C, A1015C, V826C, and L948C; or

(f) any combination of (a)-(e).

92. The RNA of any one of embodiments 63-91, wherein the S2 domain comprises one or more Pro substitions and one or more mutations that can lead to the formation of a disulfide bond.

93. The RNA of any one of embodiments 63-92, wherein the S2 domain comprises one of the following combinations of mutations relative to SEQ ID NO: 1, or a corresonding combination of mutations of an S2 domain of a SARS-CoV-2 variant:

(a) A892P, A899P, 941, K986P, V987P, G999C, and I770C;

(b) A892P, A899P, A942P, V987P, V707C, T883C, optionally wherein the S2 domain compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(c) A892P, A899P, A942P, V987P, V707C, T883C, F970C, G999C, optionally wherein the S2 domain compises one or more Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1.

94. The RNA of any one of embodiments 63-93, wherein the S2 domain comprises one or more mutations that can prevent or result in the reduction of cleavage at the S2' cleavage site.

95. The RNA of any one of embodiments 63-94, wherein the S2 domain comprises one or more mutations that can remove the S2' protease cleavage site.

96. The RNA of any one of embodiments 63-95, wherein the S2 domain comprises one or more mutations at positions corresponding to amino acids 814 and/or 815 of SEQ ID NO: 1, optionally wherein the one or more mutations are a Gly, Ser, or Ala substition (e.g., a Gly substition).

97. The RNA of embodiment 96, wherein the S2 domain comprises Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1.

98. The RNA of any one of embodiments 63-97, wherein the S2 domain comprises one or more Pro substitutions that can stabilize the S2 domain and one or more mutations that disrupt the S2' protease cleavage site.

99. The RNA of any one of daism 63-98, wherein the S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1: A892P, A899P, A942P, K986P, V987P, or any combination thereof, or corresponding mutations in a SARS-Cov-2 variant, and a Gly substituion at positions 814 and/or 815 of SEQ ID NO: 1. 100. The RNA of any one of embodiments 63-99, wherein the S2 domain comprises one or more substitutions of a hydrophillic amino acid for a hydrophobic amino acid, wherein the one or more hydrophobic amino acids are at positions that are solvent explosed in the S2 domain.

101. The RNA of embodiment 100, wherein the S2 domain comprises a substitution of a hydrophillic amino acid at one or more positions corresponding to amino acid 855, 861, 864, 976, or 984 of SEQ ID NO: 1, or any combination thereof.

102. The RNA of any one of embodiments 63-101, wherein the S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1 F855S, L861E, L864D, V976D, and L984Q, or any combination thereof, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

103. The RNA of any one of embodiments 63-102, wherein the S2 domain comprises an amino acid substitution at one or more of the amino acids at positions 901, 1020, 1058, or any combination thereof relative to SEQ ID NO: 1, or corresponding substitutions in an S2 domain of a SARS-CoV-2 variant.

104. The RNA of any one of embodiments 63-103, wherein the construct comprises one or more of the following mutations relative to SEQ ID NO: 1: Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

105. The RNA of one of embodiments 63-104, wherein the S2 domain comprises:

(a) one or more of the following mutations: S375C, T859C, Q901M, A1020Q, H1058Y, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1, Pro substitutions at positions corresponding to amino acids K986P and/or V987P of SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(b) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, and Pro substiutions at positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1, wherein mutations are shown relative to SEQ ID NO: 1, and optionally a Gly substition at one or both of the positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1;

(c) one or more of the following mutations: S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, or any combination thereof, or corresponding mutations in an S protein of a SARS-CoV-2 variant, wherein mutations are shown relative to SEQ ID NO: 1; or

(d) any combination of (a)-(c).

106. The RNA of any one of embodiments 63-105, wherein the S2 domain comprises one or more subsitions of a hydrophobic residue for a hydrophillic residue at one or more positions that are solvent buried in the context of the full length S protein, but which are solvent exposed in the absense of the SI domain.

107. The RNA of embodiment 106, wherein the one or more hydrophic residues include F855S, L861E, L864D, V976D, and L984Q, where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 domain of a SARS-CoV-2 variant.

108. The RNA of any one of embodiments 63-107, wherein the S2 domain comprises one or more of the following mutations: L861E, L864D, V976D, and L984Q, a Pro substitution at one or more positions corresponding to amino acids F817P, A892P, A899P, A942P, or combinations thereof of SEQ ID NO: 1, optionally in combination with a Pro substitution at one or both positions corresponding to amino acids K986P and V987P of SEQ ID NO: 1; or where mutations are indicated relative to SEQ ID NO: 1, or corresponding mutations in an S2 polypeptide of a SARS-CoV-2 variant.

109. The RNA of any one of embodiments 1-108, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 462 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 462; (ii) the nucleotide sequence of SEQ ID NO: 463 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 463; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 188, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 188.

110. The RNA of any one of embodiments 1-108, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 469 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 469; (ii) the nucleotide sequence of SEQ ID NO: 470 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 470; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 444, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 444.

111. The RNA of any one of embodiments 1-108, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 471 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 471; (ii) the nucleotide sequence of SEQ ID NO: 472 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 472; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 445, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 445.

112. An RNA comprising a nucleotide sequence encoding a polypeptide, where the polypeptide comprises:

(i) an RBD, and

(ii) a stem helix and a fusion peptide of an S2 domain.

113. The RNA of embodiment 112, wherein the stem helix and the fusion peptide are connected via a non- endogenous peptide sequence.

114. The RNA of embodiments 112 or 113, wherein the stem helix and the fusion peptide are directly linked to one another and/or wherein the stem helix and the fusion peptide are connected via a sequence that comprises a flexible linker.

115. The RNA any any one of embodiments 112-114, wherein the RBD is connected to the stem helix and/or the fusion peptide via a non-endogenous sequence.

116. The RNA of embodiment 115, wherein the RBD is directly linked to the stem helix and/or the fusion peptide.

117. The RNA of any one of embodiments 112-115, wherein the RBD is linked to the stem heli and/or the fusion peptide via a flexible linker.

118. The RNA of any one of embodiments 112-117, wherein the RBD is N-terminal to the stem helix and the fusion peptide.

119. The RNA of any one of embodiments 112-117, wherein the RBD is C-Terminal to the stem helix and the fusion peptide. 120. The RNA of any one of embodiments 112-119, wherein the N-terminal to C-terminal order of the RBD, stem helix, and fusion peptide is: (RBD)-(stem helix)-(fusion peptide), or (stem helix)-(fusion peptide)-(RBD), optionally wherein there is one or more linkers (e.g., a flexible linker) and/or domains (e.g., transmembrane domain or multimerization domains) between one or more of the RBD, stem helix, and fusion peptide.

121. The RNA of any one of embodiments 112-120, wherein the stem helix and the fusion peptide are directly linked to one another, and wherein the RBD is N-termina or C-terminal to the stem helix-fusion peptide region.

122. The RNA of any one of embodiments 112-121, wherein the polypeptide comprises a transmembrane domain.

123. The RNA of embodiment 120, wherein the transmembrane is at the N-terminus or the C-terminus of the polypeptide.

124. The RNA of embodiment 122 or 123, wherein the N-terminal to C-terminal configuration of the polypeptide is:

(a) (transmembrane domain)-(stem helix)-(fusion peptide)-(RBD); or

(b) (transmembrane domain)-(RBD)-(stem helix)-(fusion peptide).

125. The RNA of embodiment 124, wherein the stem helix, the fusion peptide, and the RBD are connected via a non-endogenous sequence

126. The RNA of any one of embodiments 112-125, wherein the fusion peptide comprises a sequence of PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto, and the stem helix comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

127. The RNA of any one of embodiments 112-126, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 464 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 464; (ii) the nucleotide sequence of SEQ ID NO: 465 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 465; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 190, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 190.

128. The RNA of any one of embodiments 112-126, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 466 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 466; (ii) the nucleotide sequence of SEQ ID NO: 467 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 467; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 191, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 191.

130. The RNA of any one of embodiments 112-129, wherein the polypeptide comprises a secretory signal peptide (e.g., a secretory signal peptide of a viral protein), optionally wherein the secretory signal peptide is at the N-terminus of the polypeptide.

131. The RNA of embodiment 130, wherein the secretory signal peptide is a secretory signal peptide of a SARS- CoV-2 S protein (e.g., wherein the secretory signal peptide comprises an amino acid sequence of MFVFLVLLPLVSSQCVNLT, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 variant). 132. The RNA of any one of embodiments 1-131, wherein the polypeptide comrpises one or more multimerization domains.

133. The RNA of embodiment 132, wherein the multimerization domain is a p-Annulus peptide, a ferritin domain, a fibritin domain, or a lumazine synthase multimerization domain.

134. The RNA of embodiment 133, wherein the p-Annulus peptide comprises SEQ ID NO: 201, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 201.

135. The RNA of embodiment 133, wherein the ferritin domain comprises:

(a) SEQ ID NO: 202, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 202; or

(b) SEQ ID NO: 203, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 203.

136. The RNA of embodiment 133, wherein the fibritin domain comprises:

(a) SEQ ID NO: 199, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 199; or

(b) SEQ ID NO: 200, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 200.

137. The RNA of embodiment 133, wherein the lumazine synthase multimerization domain comprises SEQ ID NO: 204, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 204.

138. An RNA comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises an antigenic fragment of an S protein, or a variant thereof, and a multimerization domain.

139. The RNA of embodiment 138, wherein the polypeptide comprises an RBD of a coronavirus S protein, an NTD of a coronavirus S protein, a truncated SI domain of a coronavirus S protein, or an S2 domain of a coronavirus S protein.

140. The RNA of embodiment 138 or 139, wherein the multimerization domain is a p-Annulus peptide, a ferritin domain, a fibritin domain, or a lumazine synthase multimerization domain.

141. The RNA of embodiment 140, wherein the p-Annulus peptide comprises SEQ ID NO: 201, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 201.

142. The RNA of embodiment 140, wherein the ferritin domain comprises:

(a) SEQ ID NO: 202, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 202; or

(b) SEQ ID NO: 203, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 203.

143. The RNA of embodiment 140, wherein the fibritin domain comprises:

(a) SEQ ID NO: 199, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 199; or

(b) SEQ ID NO: 200, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 200. 144. The RNA of embodiment 140, wherein the lumazine synthase multimerization domain comprises SEQ ID NO: 204, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 204.

145. The RNA of any one of embodiments 132-144, wherein:

(a) the antigenic fragment of the coronavirus S protein comprises an RBD and wherein the multimerization domain comprises a p-Annulus peptide;

(b) the antigenic fragment of the coronavirus S protein comprises an RBD and wherein the multimerization domain comprises a ferritin domain;

(c) the antigenic fragment of the coronavirus S protein comprises an RBD and wherein the multimerization domain comprises a lumazine synthase multimerization domain;

(d) the antigenic fragment of the coronavirus S protein comprises a truncated SI domain and wherein the multimerization domain comprises a p-Annulus peptide;

(e) the antigenic fragment of the coronavirus S protein comprises a truncated SI domain and wherein the multimerization domain comprises a ferritin domain;

(f) the antigenic fragment of the coronavirus S protein comprises a truncated SI domain and wherein the multimerization domain comprises a lumazine synthase multimerization domain;

(g) the antigenic fragment of the coronavirus S protein comprises an S2 domain and wherein the multimerization domain comprises a p-Annulus peptide;

(h) the antigenic fragment of the coronavirus S protein comprises an S2 domain and wherein the multimerization domain comprises a ferritin domain; or

(i) the antigenic fragment of the coronavirus S protein comprises an S2 domain and wherein the multimerization domain comprises a lumazine synthase multimerization domain. 146. The RNA of any one of embodiments 142-145, wherein the antigenic fragment of the coronavirus S protein and the multimerization domain are connected to one another via a linker.

147. The RNA of embodiment 146, wherein the linker is a flexible linker, a rigid linker, or a helical linker.

148. The RNA of embodiment 146 or 147, wherein the linker is a flexible linker and comprises a GS linker (e.g., wherein the GS linker 5, 10, 15, or 20 amino acids in length), optioanlly wherein the GS linker comprises a sequence of (G4S)1, (G4S)2, (G4S)3, or (G4S)4.

149. The RNA of any one of embodiments 132-148, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

150. The RNA of any one of embodiments 132-149, wherein the antigenic fragment of a SARS-CoV-2 S protein comprises an RBD and an NTD of a SARS-CoV-2 S protein.

151. The RNA of any one of embodiments 132-150, wherein the immunogenic fragment of a SARS-CoV-2 S protein comprises a truncated SI domain.

152. The RNA of embodiment 151, where an RBD is at the C-terminus of the truncated SI domain (e.g., wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant).

153. The RNA of embodiment 151 or 152, wherein the polypeptide comprises amino acids 14-528 of SEQ ID NO: 1, amino acids 17-528 of SEQ ID NO: 20-528 of SEQ ID NO: 1, amino acids 14-541 of SEQ ID NO: 1, amino acids 17-541 of SEQ ID NO: 1, or amino acids 20-541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing from an S protein of a SARS-CoV-2 variant.

154. The RNA of any one of embodiments 132-153, wherein the polypeptide comprises SEQ ID NO: 205, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 205.

155. The RNA of any one of embodiments 132-153, wherein the polypeptide comprises SEQ ID NO: 206, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 206.

156. The RNA of any one of embodiments 132-153, wherein the polypeptide comprises SEQ ID NO: 207, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 207.

157. The RNA of any one of embodiments 132-153, wherein the polypeptide comprises SEQ ID NO: 208, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 208.

158. The RNA of any one of embodiments 132-153, wherein the polypeptide comprises SEQ ID NO: 209, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 209.

159. The RNA of any one of embodiments 132-153, wherein the polypeptide comprises SEQ ID NO: 210, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 210.

160. The RNA of any one of embodiments 132-159, wherein:

(a) the RNA comprises a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 211, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 211;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 212, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 212; and/or

(c) the RNA comprises a nucleotide sequence of SEQ ID NO: 212, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 214.

161. An RNA comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises an immunogenic fragment of a SARS-CoV-2 S protein, and one or more domains that can induce formation of a viral-like particle (VLP) when the RNA is transfected into a cell.

162. The RNA of embodiment 161, wherein the one or more domains that can induce formation of a VLP comprise an endosomal sorting complex required for transport (ESCRT)- and ALG-2-interacting protein X (ALIX) binding region (collectively referred to as EABR).

163. The RNA of embodiment 162, wherein the EABR sequence comprises an amino acid sequence of FNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLLAKIFELEKKTETAAHSLP, or sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to FNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLLAKIFELEKKTETAAHSLP.

164. The RNA of embodiment 162, wherein the EABR sequence comprises an amino acid sequence of LQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to

LQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ.

165. The RNA of any one of embodiments 162-164, wheren the polypeptide further comprises a transmembrane domain.

166. The RNA of embodiment 165, wherein the transmembrane domain is a heterologous transmembrane domain or a homologous transmembrane domain.

167. The RNA of embodiment 166, wherein the transmembrane domain is or comprises a SARS-CoV-2 S protein transmembrane domain.

168. The RNA of any one of embodiments, 165-167, wherein the transmembrane domain comprises an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC.

169. The RNA of any one of embodiments 165-168, wherein the EABR and the transmembrane domain are C- terminal to the SARS-CoV-2 S protein fragment.

170. The RNA of any one of embodiments 165-169, wherein the EABR sequence is C-terminal to the transmembrane domain.

171. The RNA of any one of embodiments 165-170, wherein the transmembrane domain and the EABR sequence are directly linked to one another, or wherein the transmembrane domain and the EABR sequence are connected via a flexible linker.

172. The RNA of embodiment 171, wherein the flexible linker is a GS linker comprising about 5, about 10, about 15, or about 20 amino acids.

173. The RNA of any one of embodiments 162-172, wherein the polypeptide comprises a peptide having an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSFNSSINNIHEMEIQLKDALEKNQQWLVYDQ QREVYVKGLLAKIFELEKKTETAAHSLP (SEQ ID NO: 441), or sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto, optionally wherein the peptide having an amino acid sequence of SEQ ID NO: 441 or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical thereto is at the C- terminus of the polypeptide.

174. The RNA of any one of embodiments 162-173, wherein the polypeptide further comprises an EPM sequence.

175. The RNA of embodment 174, wherein the EPM sequence comprises ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY, or sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, identical to ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY.

176. The RNA of any one of embodiments 162-175, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an RBD, a truncated SI subdomain, and/or an S2 domain, optionally wherein the S2 domain comprises one or more mutations that increase stability.

177. The RNA of embodiment 176, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant. 178. The RNA of any one of embodiments 162-177, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an N-Terminal Domain (NTD).

179. The RNA of embodiment 178, wherein the NTD comprises amino acids 14-209, 14-303, 20-318, or 20- 302 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

180. The RNA of any one of embodiments 162-179, wherein the immunogenic fragment comprises an SI domain of a SARS-CoV-2 S protein, or an immunogenic fragment thereof.

181. The RNA of any one of embodiments 162-180, wherein the immunogenic fragment of a SARS-CoV-2 S protein comprises an RBD and an NTD of a SARS-CoV-2 S protein.

182. The RNA of any one of embodiments 162-181, wherein the immunogenic fragment of a SARS-CoV-2 S protein is a truncated SI subdomain.

183. The RNA of embodiment 182, where an RBD is at the C-terminus of the truncated SI.

184. The RNA of any one of embodiments 162-183, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises amino acids 14-528 of SEQ ID NO: 1, amino acids 17-528 of SEQ ID NO: 20-528 of SEQ ID NO: 1, amino acids 14-541 of SEQ ID NO: 1, amino acids 17-541 of SEQ ID NO: 1, or amino acids 20-541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing from an S protein of a SARS-CoV-2 variant.

185. The RNA of any one of embodiments 162-184, wherein the polypeptide comprises an amino acid sequence of VRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNFAPFFAFKCYGVSPTKLNDLCFTNVYADSFVIRGNEVSQIAP GQTGNIADYNYKLPDDFTGCVIAWNSNKLDSKPSGNYNYLYRLFRKSKLKPFERDISTEIYQAGNKPCNGVAGPNCYSPLQSYGF RPTYGVGHQPYRWVLSFELLHAPATVCGPKGSPGSGSGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSGSEQYIKWPWYI WLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSFNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLL AKIFELEKKTETAAHSLP, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

186. The RNA of any one of embodiments 162-185, wherein the polypeptide comprises an amino acid sequence of MFVFLVLLPLVSSQCVNLIVRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNFAPFFAFKCYGVSPTKLNDLCFTN VYADSFVIRGNEVSQIAPGQTGNIADYNYKLPDDFTGCVIAWNSNKLDSKPSGNYNYLYRLFRKSKLKPFERDISTEIYQAGNKP CNGVAGPNCYSPLQSYGFRPTYGVGHQPYRVWLSFELLHAPATVCGPKGSPGSGSGSGYIPEAPRDGQAYVRKDGEWVLLSTF LGSGSGSEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSFNSSINNIHEMEIQLKDALEKNQQ WLVYDQQREVYVKGLLAKIFELEKKTETAAHSLP, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

187. The RNA of any one of embodiments 148-185, wherein the polypeptide comprises an amino acid sequence of VRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNFAPFFAFKCYGVSPTKLNDLCFTNVYADSFVIRGNEVSQIAP GQTGNIADYNYKLPDDFTGCVIAWNSNKLDSKPSGNYNYLYRLFRKSKLKPFERDISTEIYQAGNKPCNGVAGPNCYSPLQSYGF RPTYGVGHQPYRWVLSFELLHAPATVCGPKGSPGSGSGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGSGSGSEQYIKWPWYI WLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSLQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLR SLFGNDPSSQ or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

188. The RNA of any one of embodiments 162-185, wherein the polypeptide comprises an amino acid sequence of MFVFLVLLPLVSSQCVNLIVRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNFAPFFAFKCYGVSPTKLNDLCFTN VYADSFVIRGNEVSQIAPGQTGNIADYNYKLPDDFTGCVIAWNSNKLDSKPSGNYNYLYRLFRKSKLKPFERDISTEIYQAGNKP CNGVAGPNCYSPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPATVCGPKGSPGSGSGSGYIPEAPRDGQAYVRKDGEWVLLSTF LGSGSGSEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSLQSRPEPTAPPEESFRSGVETTTP PQKQEPIDKELYPLTSLRSLFGNDPSSQ or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

189. The RNA of any one of embodiments 162-174, wherein:

(a) the RNA comprises a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 389 or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto;

(b) the RNA comprises a nucleotide sequence that comprises a nucleotide sequence of SEQ ID NO: 390 or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto; and/or

(c) the RNA comprises a nucleotide sequence that comprises a nucleotide sequence of SEQ ID NO: 392 or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

190. The RNA of embodiment 161, wherein the one or more domains that can induce formation of a VLP comprise VSV-G transmembrane domain.

191. The RNA of embodiment 190, wherein the VSV-G transmembrane domain comprises an amino acid sequence of KLKHTKKRQIYTDIEMNRLGK, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to KLKHTKKRQIYTDIEMNRLGK.

192. The RNA of embodiment 190 or 191, wherein the VSV-G transmembrane domain comprises a sequence that is endogenously proximal to the membrane in the VSV-G protein.

193. The RNA of embodiment 192, wherein the sequence that is endogenously proximal to the membrane in the VSV-G protein comprises:

(a) an amino acid sequence of IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI;

(b) an amino acid sequence of FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI;

(c) an amino acid sequence of

QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI; or

(d) an amino acid sequence of

FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIor an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI.

193. The RNA of any one of embodiments 190-192, wherein the VSV-G membrane proximal region comprises: (a) an amino acid sequence of IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK;

(b) an amino acid sequence of FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to FFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK;

(c) an amino acid sequence of QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to QDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK; or

(d) an amino acid sequence of FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNR LGKor an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNR LG.

194. The RNA of any one of embodiments 190-193, wherein the VSV-G transmembrane domain is at the C- terminus of the polypeptide.

195. The RNA of any one of embodiments 190-204, wherein the immunogenic fragment of the S protein and the VSV-G transmembrane domain are directly linked to one another or are linked via a linker sequence.

196. The RNA of embodiment 195, wherein the linker sequence is a GS linker sequence, and optionally comprises about 5-20 amino acids.

197. The RNA of embodiment 196, wherein the GS linker sequence comprises about 5 to about 10 amino acids.

198. The RNA of any one of embodiments 190-197, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an RBD, a truncated SI subdomain, and/or an S2 domain, optionally wherein the S2 domain comprises one or more mutations that increase stability.

199. The RNA of embodiment 198, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

200. The RNA of any one of embodiments 190-209, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an N-Terminal Domain (NTD).

201. The RNA of embodiment 200, wherein the NTD comprises amino acids 14-209, 14-303, 20-318, or 20-302 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

202. The RNA of any one of embodiments 190-201, wherein the immunogenic fragment comprises an SI domain of a SARS-CoV-2 S protein, or an immunogenic fragment thereof.

203. The RNA of any one of embodiments 190-202, wherein the immunogenic fragment of a SARS-CoV-2 S protein comprises an RBD and an NTD of a SARS-CoV-2 S protein. 204. The RNA of any one of embodiments 190-203, wherein the immunogenic fragment of a SARS-CoV-2 S protein is a truncated SI subdomain.

205. The RNA of embodiment 204, where an RBD is at the C-terminus of the truncated SI.

206. The RNA of any one of embodiments 190-205, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises amino acids 14-528 of SEQ ID NO: 1, amino acids 17-528 of SEQ ID NO: 20-528 of SEQ ID NO: 1, amino acids 14-541 of SEQ ID NO: 1, amino acids 17-541 of SEQ ID NO: 1, or amino acids 20-541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing from an S protein of a SARS-CoV-2 variant.

207. The RNA of any one of embodiments 190-206, wherein:

(a) the polyepptide comprises an amino acid sequence of SEQ ID NO: 411, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 411;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 412, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 412; and/or

(c) the RNA comprises a nucleotide sequence of SEQ ID NO: 414, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 414.

208. The RNA of any one of embodiments 190-206, wherein:

(a) the polyepptide comprises an amino acid sequence of SEQ ID NO: 406, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 406;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 407, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 407; and/or

(c) the RNA comprises a nucleotide sequence of SEQ ID NO: 409, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 409.

209. The RNA of any one of embodiments 190-206, wherein:

(a) the polyepptide comprises an amino acid sequence of SEQ ID NO: 416, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 416;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 417, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 417; and/or

(c) the RNA comprises a nucleotide sequence of SEQ ID NO: 419, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 419.

210. The RNA of any one of embodiments 190-206, wherein:

(a) the polyepptide comprises an amino acid sequence of SEQ ID NO: 421, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 421;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 422, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 422; and/or

(c) the RNA comprises a nucleotide sequence of SEQ ID NO: 424, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 424.

211. The RNA of any one of embodiments 190-206, wherein:

(a) the polypeptide comprises an amino acid sequence of SEQ ID NO: 426, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 426;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 427, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 427; and/or (c) the RNA comprises a nucleotide sequence of SEQ ID NO: 428, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 428.

212. The RNA of any one of embodiments 190-206, wherein:

(a) the polyepptide comprises an amino acid sequence of SEQ ID NO: 431, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 431;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 432, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 432; and/or

(c) the RNA comprises a nucleotide sequence of SEQ ID NO: 434, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 434.

213. The RNA of any one of embodiments 190-206, wherein:

(a) the polyepptide comprises an amino acid sequence of SEQ ID NO: 436, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 436;

(b) the RNA comprises a nucleotide sequence of SEQ ID NO: 437, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 437; and/or

(c) the RNA comprises a nucleotide sequence of SEQ ID NO: 438, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 438.

213. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 475 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 475; (ii) the nucleotide sequence of SEQ ID NO: 176 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 476; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 474, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 474.

214. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 480 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 480; (ii) the nucleotide sequence of SEQ ID NO: 482 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 482; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 479, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 479.

215. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 484 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 484; (ii) the nucleotide sequence of SEQ ID NO: 486 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 486; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 483, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 483.

216. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 489 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 489; (ii) the nucleotide sequence of SEQ ID NO: 491 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 491; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 488, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 488.

217. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 494 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 494; (ii) the nucleotide sequence of SEQ ID NO: 496 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 496; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 493, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 493.

218. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 499 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 499; (ii) the nucleotide sequence of SEQ ID NO: 501 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 501; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 498, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 498.

219. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 504 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 504; (ii) the nucleotide sequence of SEQ ID NO: 506 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 506; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 503, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 503.

220. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 509 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 509; (ii) the nucleotide sequence of SEQ ID NO: 511 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 511; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 508, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 508.

221. The RNA of any one of embodiments 190-206, wherein the RNA comprises (i) the nucleotide sequence of SEQ ID NO: 514 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 514; (ii) the nucleotide sequence of SEQ ID NO: 516 or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 516; and/or (iii) comprises a nucleotide sequence that encodes a polypeptide comprising SEQ ID NO: 513, or a sequence that is at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical to SEQ ID NO: 513.

222. The RNA of embodiment 161, wherein the one or more domains that can induce formation of a VLP comprise a VP40 TSG101 peptide and/or a p6 Alix peptide. 223. The RNA of embodiment 222, wherein the VP40 TSG101 peptide comprises an amino acid sequence of VILPTAPPEYMEA, or an amino acid sequence having 1, 2, 3, 4, or 5 modifications relative to VILPTAPPEYMEA.

224. The RNA of embodiment 222 or 223, wherein the p6 Alix peptide comprises:

(a) an amino acid sequence of DKELYPLTSLRSLFGN, or an amino acid sequence having 1, 2, 3, 4, or 5 modifications relative to DKELYPLTSLRSLFGN; or

(b) an amino acid sequence of TQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE, or an amino acid sequence having 1, 2, 3, 4, or 5 modifications relative to TQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE.

225. The RNA of any one of embodiments 222-224, wherein the p6 Alix peptide and the VP40 TSG101 peptide are directly linked to one anotheer, or wherein the p6 Alix peptide and the VP40 TSG101 peptide are connected via a linker.

226. The RNA of embodiment 225, wherein the linker is a flexible linker, and optionally comprises a GS linker (e.g., wherein the GS linker is about 5 to about 20 amino acids in length, including, e.g., about 5, about 10, about 15, or 20 amino acids in length).

227. The RNA of any one embodiments 222-226, wherein the polypeptide comprises an amino acid sequence of VILPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN, or or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to VILPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN.

228. The RNA of any one embodiments 222-226, wherein the polypeptide comprises an amino acid sequence of PTAPPEYGSGSGSLYPLTSLRSLGSGSGSPTAPGSGSGSLYPDLNLDSLGSGSGSPSAP, or or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to PTAPPEYGSGSGSLYPLTSLRSLGSGSGSPTAPGSGSGSLYPDLNLDSLGSGSGSPSAP.

229. The RNA of any one of embodiments 222-228, wherein the polypeptide comprises a transmembrane domain, where the transmembrane domain is a homologous transmembrane domain or a heterologous transmembrane domain.

230. The RNA of embodiment 229, wherein the transmembrane domain comprises a SARS-CoV-2 transmembrane domain, optionally wherein the SARS-CoV-2 transmembrane domain comprises an amino acid sequence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC.

231. The RNA of any of embodiments 222-230, wherein the one or more domains that can induce formation of a VLP comprising an amino acid seuqence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGS VILPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

232. The RNA of any of embodiments 222-231, wherein the one or more domaisn that can induce formation of a VLP comprising an amino acid seuqence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSVILPTAPPEYMEAGSGSGSTQNLYPDLSEIK KEYNVKEKDQVEDLNLDSLWE or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

233. The RNA of any of embodiments 222-232, wherein the one or more domains that can induce formation of a VLP comprising an amino acid seuqence of EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCGSGSGSPTAPPEYGSGSGSLYPLTSLRSLGSGSGSPT APGSGSGSLYPDLNLDSLGSGSGSPSAP or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

234. The RNA of embodiment 229-233, wherein the VP40 TSG101 peptide and/or p6 Alix peptide are C- terminal to the transmembrane domain.

235. The RNA of any one of embodiments 229-234, wherein the transmembrane domain and the VP40 TSG101 peptide and/or a p6 Alix peptide are C-terminal to the immunogenic fragment of the SARS-CoV-2 S protein.

236. The RNA of any one of embodiments 222-235, wherein the VP40 TSG101 peptide and/or p6 Alix peptide are at the C-terminus of the polypeptide.

237. The RNA of any one of embodiments 222-236, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an RBD, a truncated SI subdomain, and/or an S2 domain, optionally wherein the S2 domain comprises one or more mutations that increase stability.

238. The RNA of embodiment 237, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

239. The RNA of any one of embodiments 222-238, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an N-Terminal Domain (NTD).

240. The RNA of embodiment 239, wherein the NTD comprises amino acids 14-209, 14-303, 20-318, or 20- 302 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

241. The RNA of any one of embodiments 222-240, wherein the immunogenic fragment comprises an SI domain of a SARS-CoV-2 S protein, or an immunogenic fragment thereof.

242. The RNA of any one of embodiments 222-241, wherein the immunogenic fragment of a SARS-CoV-2 S protein comprises an RBD and an NTD of a SARS-CoV-2 S protein.

243. The RNA of any one of embodiments 222-242, wherein the immunogenic fragment of a SARS-CoV-2 S protein is a truncated SI subdomain.

244. The RNA of embodiment 243, where an RBD is at the C-terminus of the truncated SI.

245. The RNA of any one of embodiments 222-244, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises amino acids 14-528 of SEQ ID NO: 1, amino acids 17-528 of SEQ ID NO: 20-528 of SEQ ID NO: 1, amino acids 14-541 of SEQ ID NO: 1, amino acids 17-541 of SEQ ID NO: 1, or amino acids 20-541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing from an S protein of a SARS-CoV-2 variant.

246. The RNA of any one of embodiments 222-245, wherein the RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 362, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical SEQ ID NO: 362.

247. The RNA of any one of embodiments 222-245, wherein the RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 362, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical SEQ ID NO: 363.

248. The RNA of any one of embodiments 222-245, wherein the RNA encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 364, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical SEQ ID NO: 364. 249. The RNA of embodiment 161, wherein the one or more domains that can induce formation of a VLP comprise a portion of a capsid protein of Porcine circovirus 2 (PCV-2).

250. The RNA of embodiment 249, wherein the portion of the capsid protein of PCV-2:

(a) comprises an amino acid sequence of

MTYPRRRYRRRRHRPRSHLGQILRRRPWLVHPRHRYRWRRKNGIFNTRLSRTFGYTVKATTVRTPSWAVDMMRFNIDDFVPP GGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVNYSSRHTIPQPFSYHSRYFTPKPVLD STIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPLKP, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to MTYPRRRYRRRRHRPRSHLGQILRRRPWLVHPRHRYRWRRKNGIFNTRLSRTFGYTVKATTVRTPSWAVDMMRFNIDDFVPP GGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVNYSSRHTIPQPFSYHSRYFTPKPVLD STIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPLKP; and/or

(b) is encoded by a nucleotide sequence of

AUGACGUAUCCAAGGAGGCGUUACCGCAGAAGAAGACACCGCCCCCGCAGCCAUCUUGGCCAGAUCCUCCGCCGCCGCCC CUGGCUCGUCCACCCCCGCCACCGCUACCGUUGGAGAAGGAAAAAUGGCAUCUUCAACACCCGCCUCUCCCGCACCUUCG GAUAUACUGUCAAGGCUACCACAGUCAGAACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUGU UCCCCCGGGAGGGGGGACCAACAAAAUCUCUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGGC CCUGCUCCCCCAUCACCCAGGGUGAUAGGGGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGGC CACAGCCCUAACCUAUGACCCAUAUGUAAACUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUUA CUUCACACCCAAACCUGUUCUUGACUCCACUAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGGC

UACAAACCUCUAGAAAUGUGGACCACGUAGGCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAUC CGUGUAACCAUGUAUGUACAAUUCAGAGAAUUUAAUCUUAAAGACCCCCCACUUAAACCC, or a nucleotide sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical toAUGACGUAUCCAAGGAGGCGUUACCGCAGAAGAAGACACCGCCCCCGCAGCCAUCUUGGCCAGAUCCUCCGCCGCCGCC CCUGGCUCGUCCACCCCCGCCACCGCUACCGUUGGAGAAGGAAAAAUGGCAUCUUCAACACCCGCCUCUCCCGCACCUUC GGAUAUACUGUCAAGGCUACCACAGUCAGAACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUG UUCCCCCGGGAGGGGGGACCAACAAAAUCUCUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGG

CCCUGCUCCCCCAUCACCCAGGGUGAUAGGGGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGG CCACAGCCCUAACCUAUGACCCAUAUGUAAACUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUU ACUUCACACCCAAACCUGUUCUUGACUCCACUAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGG CUACAAACCUCUAGAAAUGUGGACCACGUAGGCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAU CCGUGUAACCAUGUAUGUACAAUUCAGAGAAUUUAAUCUUAAAGACCCCCCACUUAAACCC.

251. The RNA of embodiment 249, wherein the portion of the capsid protein of PCV-2:

(a) comprises an amino acid sequence of

TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVNYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPP, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVNYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPP; and/or (b) is encoded by a nucleotide sequence of

ACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUGUUCCCCCGGGAGGGGGGACCAACAAAAUCU CUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGGCCCUGCUCCCCCAUCACCCAGGGUGAUAGG GGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGGCCACAGCCCUAACCUAUGACCCAUAUGUAAA CUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUUACUUCACACCCAAACCUGUUCUUGACUCCAC UAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGGCUACAAACCUCUAGAAAUGUGGACCACGUAG GCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAUCCGUGUAACCAUGUAUGUACAAUUCAGAGAA UUUAAUCUUAAAGACCCCCCACUU, or a nucleotide sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical

ACGCCCUCCUGGGCGGUGGACAUGAUGAGAUUUAAUAUUGACGACUUUGUUCCCCCGGGAGGGGGGACCAACAAAAUCU CUAUACCCUUUGAAUACUACAGAAUAAGAAAGGUUAAGGUUGAAUUCUGGCCCUGCUCCCCCAUCACCCAGGGUGAUAGG GGAGUGGGCUCCACUGCUGUUAUUCUAGAUGAUAACUUUGUAACAAAGGCCACAGCCCUAACCUAUGACCCAUAUGUAAA CUACUCCUCCCGCCAUACAAUCCCCCAACCCUUCUCCUACCACUCCCGUUACUUCACACCCAAACCUGUUCUUGACUCCAC UAUUGAUUACUUCCAACCAAAUAACAAAAGGACUCAGCUUUGGCUGAGGCUACAAACCUCUAGAAAUGUGGACCACGUAG GCCUCGGCACUGCGUUCGAAAACAGUAUAUACGACCAGGACUACAAUAUCCGUGUAACCAUGUAUGUACAAUUCAGAGAA UUUAAUCUUAAAGACCCCCCACUU.

252. The RNA of embodiment 249, wherein the portion of the capsid protein of PCV-2 comprises an amino acid sequence of

TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVDYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPL, or an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

TPSWAVDMMRFNIDDFVPPGGGTNKISIPFEYYRIRKVKVEFWPCSPITQGDRGVGSTAVILDDNFVTKATALTYDPYVDYSSR HTIPQPFSYHSRYFTPKPVLDSTIDYFQPNNKRTQLWLRLQTSRNVDHVGLGTAFENSIYDQDYNIRVTMYVQFREFNLKDPPL.

253. The RNA of any one of embodiments 249-252, wherein the portion of the PCV-2 capside protein is at the C-terminus of the polypeptide.

254. The RNA of any one of embodiments 249-253, wherein the polypeptide comprises a trimerization domain (e.g., a fibritin domain), optionally wherein the trimerization domain is C-terminal to the immunogenic fragment of the SARS-CoV-2 S protein.

255. The RNA of any one of embodiments 249-254, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an RBD.

256. The RNA of embodiment 255, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of a SARS-CoV-2 variant.

257. The RNA of any one of embodiments 249-256, wherein the immunogenic fragment of the SARS-CoV-2 S protein comprises an N-Terminal Domain (NTD).

258. The RNA of embodiment 257, wherein the NTD comprises amino acids 14-209, 14-303, 20-318, or 20- 302 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

259. The RNA of any one of embodiments 249-258, wherein the immunogenic fragment comprises an SI domain of a SARS-CoV-2 S protein, or an immunogenic fragment thereof. 260. The RNA of any one of embodiments 249-259, wherein the immunogenic fragment of a SARS-CoV-2 S protein comprises an RBD and an NTD of a SARS-CoV-2 S protein.

261. The RNA of any one of embodiments 249-260, wherein the immunogenic fragment of a SARS-CoV-2 S protein is a truncated SI subdomain.

262. The RNA of embodiment 261, where an RBD is at the C-terminus of the truncated SI subdomain.

263. The RNA of embodiment 262, wherein the polypeptide comprises amino acids 14-528 of SEQ ID NO: 1, amino acids 17-528 of SEQ ID NO: 20-528 of SEQ ID NO: 1, amino acids 14-541 of SEQ ID NO: 1, amino acids 17-541 of SEQ ID NO: 1, or amino acids 20-541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing from an S protein of a SARS-CoV-2 variant.

264. The RNA of any one of embodiments 161-263, wherein the polypeptide comprises a secretory signal peptide, and wherein the secretory signal peptide is a homologous secretory signal peptide or a heterologous secretory signal peptide.

265. The RNA of embodiment 264, wherein the heterologous secretory signal peptide is a secretory signal peptide of a viral protein that is not a SARS-CoV-2 S protein.

266. The RNA of any one of embodiments 161-265, wherein the polypeptide comprises a secretory signal peptide that comprises (i) an amino acid sequence that is listed in Table 2 or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to an amino acid sequence that is listed in Table 2, and/or (ii) wherein the RNA comprises a nucleotide sequence that is listed in Table 3 or a nucleotide sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to an amino acid sequence that is listed in Table 2.

267. The RNA of any one of embodiments 161-266, wherein the polypeptide sequence comprises an SP24- Q7PUJ5_ANOGA secretory signal peptide (e.g., a secretory signal peptide comprising an amino acid sequence of MCRGLSAVLILLVSLSAQLHWVG or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MCRGLSAVLILLVSLSAQLHWVG.

268. The RNA of any one of embodiments 161-266, wherein the polypeptide sequence comprises an SP24- SP18-HEMA_CVBM secretory signal peptide (e.g., a secretory signal peptide comprising the amino acid sequence of MFLLLRFVLVSCIIGSLG or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MFLLLRFVLVSCIIGSLG.

269. The RNA of any one of embodiments 161-266, wherein the polypeptide sequence comprises an SP25- GD_HHV1K secretory signal peptide (e.g., a secretory signal peptide comprising an amino acid sequence of MGGAAARLGAVILFWIVGLHGVRG or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MGGAAARLGAVILFWIVGLHGVRG.

270. The RNA of any one of embodiments 161-266, wherein the polypeptide sequence comprises an SP32- GB_HHV1K secretory signal peptide (e.g., a secretory signal peptide comprising the amino acid sequence of MHQGAPSWGRRWFWWALLGLTLGVLVASAAP or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to

M HQGAPSWGRRWFWWALLGLTLGVLVASAAP.

271. The RNA of any one of embodiments 161-266, wherein the polypeptide sequence comprises an SP20- A7U881_HHV2 secretory signal peptide (e.g., a secretory signal peptide comprising the amino acid sequence of MARGAGLVFFVGVWWSCLA or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to MARGAGLVFFVGVWWSCLA. 272. The RNA of any one of the preceding embodiments, wherein the RNA comprises a 5' cap, a cap proximal sequence, a 5' UTR sequence, a 3' UTR sequence, and a polyA sequence.

273. The RNA of embodiment 272, wherein:

(i) the 5' cap comprises a Capl structure;

(ii) the 5'-UTR sequence comprises a modified human alpha-globin 5'-UTR;

(iii) the 3'-UTR sequence comprises a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA;

(iv) the polyA sequence comprises at least 100 A nucleotides; or

(v) a combination of any one of (i)-(iv).

274. The RNA of embodiment 272 or 273, wherein the 5' cap comprising a Capl structure, and the Capl structure comprises m7(3'OMeG)(5')ppp(5')(2'OMeAl)pG2, wherein Al is position +1 of the RNA, and G2 is position +2 of the RNA.

275. The RNA of embodiment 274, wherein the cap proximal sequence comprises Al and G2 of the Capl structure, and a sequence comprising: A3N4N5 at positions +3, +4 and +5 respectively of the RNA, wherein N4 and N5 are each independently selected from A, G, C, and U.

276. The RNA of any one of embodiments 272-275; wherein the polyA sequence comprises an interrupted sequence of A nucleotides, optionally wherein the interrupted sequence comprises 30 adenine nucleotides followed by 70 adenine nucleotides, wherein the 30 adenine nucleotides and 70 adenine nucleotides are separated by a linker sequence.

277. The RNA of any one of embodiments 272-276, wherein the 5'-UTR sequence comprises SEQ ID NO: 12, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 12.

278. The RNA of any one of embodiments 272-277, wherein: the 3'-UTR sequence comprises SEQ ID NO: 13, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 13; the 3'-UTR sequence comprises SEQ ID NO: 601, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 601; the 3'-UTR sequence comprises SEQ ID NO: 602, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 602.

279. The RNA of any one of embodiments 272-278, wherein the interrupted polyA tail sequence comprises SEQ ID NO: 14, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 14.

280. The RNA of any one of embodiments 272-279, wherein the sequence at the 5' end of the 3'UTR sequence (e.g., the sequence immediately adjacent to a sequence encoding an antigenic polypeptide) is CUCGAG or GGAUCCGAU.

281. The RNA of any one of the preceding embodiments, wherein the RNA is saRNA, self-amplifying RNA, trans-amplifying RNA (taRNA), or mRNA.

282. The RNA of any one of the preceding embodiments, wherein the RNA is unmodified RNA or wherein the RNA comprises one or modified uridines in place of one or more uridines.

283. The RNA of any one of the preceding embodiments, wherein the RNA comprises a single modified uridine in place of each uridine. 284. The RNA of embodiment 282 or 283, wherein the modified uridine is Nl-methyl-pseudouridine.

285. The RNA of any one of the preceding embodiments, wherein the nucleotide sequence encoding the SARS-CoV-2 S protein is encoded by a sequence that is codon-optimized (e.g., codon-optimized for expression in human cells) and/or which has a G/C content that is increased compared to a wild type coding sequence.

286. A composition comprising an RNA of any one of embodiments 1-285.

287. The composition of embodiment 286, wherein the RNA is formulated in a nanoparticle.

288. The composition of embodiment 287, wherein the nanopartide is a lipid nanoparticle, a polyplex (PLX), a lipidated polyplex (LPLX), a liposome, or a polysaccharide nanoparticle.

289. The composition of embodiment 288, wherein the nanopartide is a lipid nanopartide.

290. The composition of embodiment 289, wherein the lipid nanopartide comprises a cationical ly ionizable lipid, a sterol, a neutral lipid, and a polymer-conjugated lipid.

291. The composition of embodiment 290, wherein the polymer-conjugated lipid comprises a PEG-conjugated lipid.

292. The composition of any one of embodiments 287 to 291, wherein the RNA is encapsulated in a lipid nanoparticle (LNP), preferably wherein the LNP comprises molar ratios of 20-60% ionizable cationic lipid, 5-25% neutral lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid.

293. The composition of any one of embodiments 287-293, wherein the nanopartides have an average diameter of about 50-150 nm.

294. The composition of any one of embodiments 286-293, comprising a cryoprotectant, optionally wherein the cryoprotectant is or comprises sucrose.

295. The composition of any one of embodiments 286-294, comprising an aqueous buffered solution, optionally wherein the aqueous buffered solution comprises one or more of Tris base, Tris HCI, NaCI, KCI, Na2HPO4, and KH2PO4.

296. The composition of any one of embodiments 286-295, comprising about 10 mM Tris buffer and about 10% sucrose.

297. A pharmaceutical composition comprising (i) an RNA of any one of embodiments 1-285 or a composition of any one of embodiments 286-296 and (ii) a pharmaceutically acceptable excipient.

298. The pharmaceutical composition of embodiment 297, wherein the pharmaceutical composition is formulated as a multi-dose formulation in a vial, a single-dose formulation in a vial, or a prefilled syringe.

299. The pharmaceutical composition of embodiment 298 or 298, formulated to provide a dose of about 100 μg or less (e.g., about 90 μg or less) of total RNA.

300. The pharmaceutical composition of embodiment 299, formulated to provide a dose of about 90 pg, about 60 pg, about 30 pg, about 25 pg, about 20 pg, about 10 pg, about 6 pg, about 5 pg, or about 3 pg of total RNA.

301. A method comprising administering an RNA of any one of embodiments 1-285, a composition of any one of embodiments 286-295, or a pharmaceutical composition of any one of embodiments 296-300 to a subject.

302. The method of embodiment 301, wherein:

(i) the subject is 12 years or older, and the method comprises administering 30 pg of the RNA,

(ii) the subject is 5 years to less than 12 years old, and the method comprises administering 10 pg of the RNA, or (iii) the subject is 6 months to less than 5 years old, and the method comprises administering 3 pg of the RNA.

303. The method of embodiment 301 or 302, wherein the composition is administered in a volume of about 200 pL to about 300 μL.

304. The method of any one of embodiments 301-303, wherein the subject has not previously been administered a SARS-CoV-2 vaccine and/or wherein the subject has not previously been determined to have been infected with SARS-CoV-2 (e.g., as determined using a PCR or antigen test).

305. The method of any one of embodiments 301-304, wherein the method comprises administering a single dose of the RNA, composition, or pharmaceutical composition to the subject.

306. The method of any one of embodiments 301-304, wherein the method comprises administering two or more doses of the RNA, composition, or pharmaceutical composition to the subject, optionally wherein the two doses are administered about 21 days apart.

307. The method of any one of embodiments 301-306, wherein RNA, composition, or pharmaceutical composition is administered three times to the subject, optionally wherein the first and the second dose are administered about 21 days apart, and the third dose is administered about 28 days after the second dose.

308. The method of any of embodiments 301-307, comprising administering a further dose of the RNA, composition, or pharmaceutical composition, at least about 2 months after the first dose of the RNA, composition, or pharmaceutical composition (e.g., 2-12 months, 2-10 months, 2-8 months, about 2 months, about 3 months, about 4 months, about 5 months, or about 6 months).

309. The method of any one of embodiments 301-308, wherein the subject has previously been exposed to a SARS-CoV-2 antigen (e.g., by vaccination and/or by infection).

310. The method of any one of embodiments 301-309, wherein the subject was previously administered one or more doses of a SARS-CoV-2 vaccine.

311. The method of embodiment 310, wherein the subject was previously administered a complete dosing regimen of a SARS-CoV-2 vaccine.

312. The method of any one of embodiments 301-311, wherein the subject was previously administered a first dose and a second dose of a vaccine that delivers a full length SARS-CoV-2 S protein (e.g., a composition comprising LNP-formulated RNA encoding a SARS-CoV-2 S protein), wherein the first dose and the second dose were administered about 21 days apart, and optionally wherein the subject was previously administered as a booster dose a monovalent or bivalent vaccine that delivers a SARS-CoV-2 S protein of one or more variants (e.g., (i) an S protein of a Wuhan strain and an S protein of an Omicron BA.4/5 strain, (ii) an S protein of an XBB.1.5 variant, (iii) an S protein of a KP.2 variant, and/or (iv) an S protein of a JN.l variant).

313. The method of any one of embodiments 301-312, further comprising administering one or more vaccines against a non-SARS-CoV-2 disease, optionally wherein the one or more vaccines comprises an RSV vaccine, an influenza vaccine, or a combination thereof.

314. The method of any one of embodiments 301-313, wherein the method results in induction of an immune response against SARS-CoV-2 in the subject.

315. The method of embodiment 314, wherein the immune response comprises a B-cell response.

316. The method or embodiment 315, wherein the B cell response comprises production of antibodies directed against one or more SARS-CoV-2 viruses. 317. The method of any one of embodiments 314-316, wherein the immune response comprises a T cell response, optionally wherein the T-cell response comprises a CD4+ T cell response and/or CD8+ T cell response.

318. The method of any one of embodiments 301-317, wherein the method is a method of preventing or reducing the chances of being infected with a SARS-CoV-2 virus and/or treating a SARS-CoV-2 infection.

319. An RNA of any one of embodiments 1-285, a composition of any one of embodiments 286-296, or a pharmaceutical composition of any one of embodiments 297-300, for use in inducing an immune response in a subject.

320. The RNA, composition, or pharmaceutical composition of embodiment 319, wherein the use comprises performing in accordance with the method of any one of embodiments 301-318.

321. Use of an RNA of any one of embodiments 1-285, a composition of any one of embodiments 286-296, or a pharmaceutical composition of any one of embodiments 297-300, for the manufacture of a medicament for inducing an immune response in a subject.

322. The use of embodiment 321, wherein the medicament is formulated to be administered to the subject in accordance with the method of any one of embodiments 301-318.

323. The use of embodiment 321 or 322, wherein the method is a method of inducing an immune response to a coronavirus in a subject, and wherein the method comprises administering the RNA of any one of embodiments

324. A method of manufacturing an RNA, comprising in vitro transcribing the RNA of any one of embodiments 1-285.

325. A ribonucleic acid (RNA) comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises:

(i) a receptor binding domain (RBD) of a coronavirus Spike (S) protein; and

(ii) an S2 domain of a coronavirus S protein or one or more fragments thereof; wherein the RBD and the S2 domain or the one or more fragments thereof are directly adjacent to one another or are connected via a non-endogenous sequence.

326. The RNA of claim 325, wherein the polypeptide comprises a stem helix and a fusion peptide of an S2 domain of a coronavirus S protein.

327. The RNA of claim 325 or 326, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

328. The RNA of any one of claims 325-327, wherein the S2 domain comprises amino acid 686-1213 of SEQ ID NO: 1, 686-1211 of SEQ ID NO: 1, amino acids 687-1206 of SEQ ID NO: 1, or amino acids 687-1211 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant, optionally wherein the S2 domain comprises one or more mutations that stabilize the S2 domain.

329. The RNA of any one of claims 325-328, wherein the S2 domain comprises:

(a) an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSN NSIAIPTN FTISVTTEILPVSMTKTSVDCTMYICGDSTECSN LLLQYGSFCTQLN RALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCG KGYH LMSFPQSAPHG WFLHVTYVPAQEKN FTTAPAICH DG KAH FPREGVFVSNGTHWFVTQRN FYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIKWP, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto;

(b) an amino acid sequence of:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQ’TYVrQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYH LMSFPQSAPHGWFLHVTYVPAQEKN FTTAPAICH DG KAH FPREG VFVSNGTHWFVTQRN FYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto;

(c) an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGVZFFGAGAALQIPFAMQMAYRFNGIGVFQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto; or

(d) an amino acid sequence of:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCG KGYH LMSFPQSAPHGWFLHVTYVPAQEKN FTTAPAICH DGKAH FPREGVFVSNGTHWFVTQRN FYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKY, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

330. The RNA of any one of claims 325-329, wherein the S2 domain comprises one or more stabilizing mutations, optionally wherein the one or more stabilizing mutations comprise one or more mutations that can stabilize the prefusion confirmation of an S protein, further optionally wherein the one or more stabilizing mutations include one or more Pro substitutions and/or one or more Cys substitutions that can result in the formation of a disulfide bond.

331. The RNA of claim 330, wherein the S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1, or corresponding mutation(s) in an S2 domain of an S protein of a SARS-CoV-2 variant:

(a) K986P and V987P;

(b) A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P;

(c) F817P, A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P; (d) V707C and T883C;

(e) I770C and A1015C;

(f) V826C and A1015C;

(g) V826C and L948C;

(h) F970C and G999C;

(I) S735C and T859C; or fl) any combination of (a)-(i).

332. The RNA of any one of claims 325-331, wherein the non-endogenous sequence comprises a flexible linker sequence.

333. The RNA of any one of claims 325-332, wherein the polypeptide does not comprise sequences of a coronavirus S protein other than that of the RBD and the S2 domain or one or more fragments thereof, and optionally wherein:

(i) the polypeptide does not comprise a SARS-CoV-2 S protein secretory signal and/or a SARS-CoV-2 S protein transmembrane domain;

(ii) the polypeptide comprises a SARS-CoV-2 S protein secretory signal and/or a SARS-CoV-2 S protein transmembrane domain.

334. The RNA of any one of claims 325-333, wherein the polypeptide comprises a stem helix (SH) and fusion peptide (FP) of an S2 domain and does not comprise sequences of other regions of the S2 domain, aside from optionally a transmembrane domain of a SARS-CoV-2 S protein.

335. The RNA of claim 334, wherein the RBD is directly adjacent to the SH and/or the FP, or wherein the RBD is connected to the SH and/or the FP via a flexible linker sequence.

336. The RNA of any one of claims 325-336, wherein the SH and the FP are directly adjacent to one another or are connected to one another via a non-endogenous sequence comprising a flexible linker sequence.

337. The RNA of any one of embodiments 325-336, wherein the RBD is N-terminal to the SH and the FP, or the RBD is C-Terminal to the SH and the FP.

338. The RNA of any one of claims 325-337, wherein the N-terminal to C-terminal orientation of the polypeptide is: (RBD)-(FP)-(SH), or (FPj-(SH)-(RBD), optionally wherein there is one or more linkers (e.g., a flexible linker) and/or domains (e.g., transmembrane domain or multimerization domains) between one or more of the RBD, stem helix, and fusion peptide.

339. The RNA of claim 348, wherein the SH and the FP are directly adjacent to one another, and wherein the RBD is N-terminal or C-terminal to the SH-FP region.

340. The RNA of any one of claims 325-339, wherein the polypeptide comprises a transmembrane domain, optionally wherein the transmembrane domain is at the N-terminus or the C-terminus of the polypeptide, further optionally wherein the transmembrane domain comprises (i) an amino acid sequence of

EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC, or an amino acid sequence that is at least 70%, 80%, 85%, 90%, or 95% identical thereto; or (ii) an amino acid sequence of (EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT, or an amino acid sequence that is at least 70%, 80%, 85%, 90%, or 95% identical thereto.

341. The RNA of claim 341, wherein the N-terminal to C-terminal orientation of the polypeptide is:

(a) (RBD)-(FP)-(SH)-(transmembrane domain); or

(b) (FP)-(SH)-(RBD)-(transmembrane domain). 342. The RNA of any one of claims 325-341, wherein the FP comprises a sequence of PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto, and the SH comprises a sequence of LQPELDSFKEELDKYFKNHTSPDV, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

343. The RNA of any one of claims 325-342, wherein the polypeptide comprises a secretory signal peptide, wherein the secretory signal peptide is a homologous or a heterologous secretory signal peptide.

344. The RNA of any one of claims 325-343, wherein the polypeptide comprises a secretory signal peptide comprising:

(i) an amino acid sequence of MFVFLVLLPLVSSQCVNLT, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 variant.

(ii) an amino acid sequence of MCRGLSAVLILLVSLSAQLHVWG or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical thereof;

(Hi) an amino acid sequence of MFLLLRFVLVSCIIGSLG or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical thereto;

(iv) an amino acid sequence of MGGAAARLGAVILFWIVGLHGVRG or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical thereto;

(v) an amino acid sequence of MHQGAPSWGRRWFWWALLGLTLGVLVASAAP or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical thereto; or

(vi) an amino acid sequence of MARGAGLVFFVGVWWSCLA or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical thereto.

345. The RNA of any one of claims 325-344, wherein the polypeptide comprises:

(a) an amino acid sequence of SEQ ID NO: 190, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 190; or

(b) an amino acid sequence of SEQ ID NO: 191, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to SEQ ID NO: 191.

346. The RNA of any one of claims 325-345, wherein the RBD comprises one or more mutations of a SARS- CoV-2 variant, optionally wherein the RBD comprises one or more mutations associated with a variant listed in Table 1 (such as JN.l, KP.2, or XEC variant, or a descendent thereof).

347. The RNA of any one of the preceeding embodiments , wherein the RNA comprises a 5' cap, a cap proximal sequence, a 5' UTR sequence, a 3' UTR sequence, and a polyA sequence; optionally wherein

(i) the 5' cap comprises a Capl structure;

(ii) the 5'-UTR sequence comprises a modified human alpha-globin 5'-UTR;

(iii) the 3 -UTR sequence comprises a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA;

(iv) the polyA sequence comprises at least 100 A nucleotides; or

(v) the RNA comprises a combination of any one of (i)-(iv).

348. The RNA of claim 347, wherein: the 5' cap comprising a Capl structure, and the Capl structure comprises m7(3'OMeG)(5')ppp(5')(2'OMeAl)pG2, wherein Al is position +1 of the RNA, and G2 is position +2 of the RNA, optionally wherein the cap proximal sequence comprises Ai and G2 of the Capl structure, and a sequence comprising: A3N4N5 at positions +3, +4 and +5 respectively of the RNA, wherein N4 and N5 are each independently selected from A, G, C, and U; and/or the polyA sequence comprises an interrupted sequence of A nucleotides, optionally wherein the interrupted sequence comprises 30 adenine nucleotides followed by 70 adenine nucleotides, wherein the 30 adenine nucleotides and 70 adenine nucleotides are separated by a linker sequence; and/or the 5'-UTR sequence comprises SEQ ID NO: 112, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 112; and/or the 3'-UTR sequence comprises SEQ ID NO: 113, or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% identical to SEQ ID NO: 113; and/or the sequence at the 5' end of the 3'UTR sequence (e.g., the sequence immediately adjacent to a sequence encoding an antigenic polypeptide) is CUCGAG or GGAUCCGAU.

349. The RNA of any one of the preceding embodiments, wherein the RNA is self-amplifying RNA (saRNA), trans-amplifying RNA (taRNA), or messenger RNA (mRNA).

350. The RNA of any one of the preceding embodiments, wherein the RNA is unmodified RNA or wherein the RNA comprises one or modified uridines in place of one or more uridines, optionally wherein the RNA comprises a single modified uridine in place of each uridine, further optionally wherein the modified uridine is Nl-methyl- pseudouridine.

351. A composition comprising an RNA of any one of embodiments 325-350, optionally wherein the RNA is formulated in a nanoparticle, further optionally wherein the nanoparticle is a lipid nanoparticle, a polyplex (PLX), a lipidated polyplex (LPLX), a liposome, or a polysaccharide nanoparticle.

352. The composition of claim 351, wherein the RNA is fully or partially encapsulated in the nanoparticle.

353. The composition of any one of claims 351-352, further comprising a cryoprotectant, optionally wherein the cryoprotectant is or comprises sucrose and/or an aqueous buffered solution, optionally wherein the aqueous buffered solution comprises one or more of Tris base, Tris HCI, NaCI, KCI, Na2HPC>4, and KH2PO4, further optionally wherein the aqueous buffered solution comprises about 10 mM Tris buffer and about 10% sucrose.

354. A pharmaceutical composition comprising (i) an RNA of any one of claims 325-350 or a composition of any one of claims 351-353 and (ii) a pharmaceutically acceptable excipient.

355. The pharmaceutical composition of claim 354, wherein the pharmaceutical composition is formulated as a multi-dose formulation in a vial, a single-dose formulation in a vial, or a prefilled syringe.

356. The pharmaceutical composition of claim 354 or 355, formulated to provide a dose of about 100 pg or less of total RNA, about 90 pg, about 60 pg, about 30 pg, about 25 pg, about 20 pg, about 10 pg, about 6 pg, about 5 pg, or about 3 μg of total RNA.

357. A method comprising administering an RNA of any one of claims 325-350, a composition of any one of claims 351-353, or a pharmaceutical composition of any one of claims 354-356 to a subject.

358. The method of claim 357, wherein:

(i) the subject is 12 years or older, and the method comprises administering 30 pg of the RNA,

(ii) the subject is 5 years to less than 12 years old, and the method comprises administering 10 pg of the RNA, or

(iii) the subject is 6 months to less than 5 years old, and the method comprises administering 3 pg of the RNA. 359. The method of claim 357 or 358, wherein the composition is administered in a volume of about 200 pL to about 300μL.

360. The method of any one of claims 357-359, wherein the method comprises administering a single dose of the RNA, composition, or pharmaceutical composition to the subject.

361. The method of any one of claims 357-359, wherein the method comprises administering two or more doses of the RNA, composition, or pharmaceutical composition to the subject, optionally wherein the two doses are administered about 21 days apart.

362. The method of any one of claims 357-361, wherein RNA, composition, or pharmaceutical composition is administered three times to the subject, optionally wherein the first and the second dose are administered about 21 days apart, and the third dose is administered about 28 days after the second dose.

363. The method of any one of claims 357-362, further comprising administering one or more vaccines against a non-SARS-CoV-2 disease, optionally wherein the one or more vaccines comprises an RSV vaccine, an influenza vaccine, or a combination thereof.

364. The method of any one of claims 357-363, wherein the method results in induction of an immune response against SARS-CoV-2 in the subject, optionally wherein the immune response comprises production of antibodies directed against one or more SARS-CoV-2 viruses and/or a T cell response (e.g., a CD4+ T cell response and/or CD8+ T cell response).

365. The method of any one of claims 357-364, wherein the method is a method of preventing SARS-CoV-2 infection, reducing the chance of SARS-CoV-2 infection, preventing or reducing the change of deleterious symptoms associated with SARS-CoV-2 infection (which can result, e.g., in a reduced change of hospitalization), increase the change of experiencing an asymptomatic SARS-CoV-2 infection, and/or treating a SARS-CoV-2 infection.

366. An RNA of any one of claims 324-350, a composition of any one of claims 351-353, or a pharmaceutical composition of any one of claims 354-356, for use in inducing an immune response in a subject, optionally wherein the use comprises performing in accordance with the method of any one of claims 357-365.

367. Use of an RNA of any one of claims 325-350, a composition of any one of claims 351-353, or a pharmaceutical composition of any one of claims 354-356, for the manufacture of a medicament for inducing an immune response in a subject, optionally wherein the medicament is formulated to be administered to the subject in accordance with the method of any one of claims 357-365.

368. A method of manufacturing an RNA, comprising in vitro transcribing the RNA of any one of claims 325- 350.

369. The RNA of embodiment 161, wherein the immunogenic fragment of a SARS-CoV-2 S protein is an S2 domain, optionally comprising one or more stabilizing mutations.

370. The RNA of embodiment 161, wherein the S2 domain is an S2 domain of any one of embodiments 1-37.

371. The RNA of embodiment 370, wherein, the one or more domains that can induce formation of a VLP comprise:

(i) an EABR of any one of claims 162-175

(ii) a VSV-G transmembrane domain of any one of claims 190-198

(iii) a VP40 TSG101 peptide and/or a p6 Alix peptide of any one of claims 222-237

(iv) a portion of a capsid protein of any one of embodiments 249-254

372. The RNA of embodiment 161, wherein the immunogenic fragment of a SARS-CoV-2 S protein comprises an S2 domain or an immunogenic fragment thereof and an RBD. 373. The RNA of embodiment 161, wherein the RNA encodes a polypeptide of any one of embodiments 63- 111 or 112-126.

374. The RNA of embodiment 373, wherein, the one or more domains that can induce formation of a VLP comprises:

(i) an EABR of any one of claims 162-175

(ii) a VSV-G transmembrane domain of any one of claims 190-198

(iii) a VP40 TSG101 peptide and/or a p6 Alix peptide of any one of claims 222-237

(iv) a portion of a capsid protein of any one of embodiments 249-254.

[001476] The following description is presented to enable a person of ordinary skill in the art to make and use the various embodiments. Descriptions of specific devices, techniques, and applications are provided only as examples. Various modifications to the examples described herein will be readily apparent to those of ordinary skill in the art, and the general principles defined herein may be applied to other examples and applications without departing from the spirit and scope of the various embodiments. Thus, the various embodiments are not intended to be limited to the examples described herein and shown, but are to be accorded the scope consistent with the claims.

Examples

Example 1: RNA (e.g., mRNA) constructs encoding an S2 protein or an immunogenic fragment thereof

[001477] The present Example describes certain improved RNA molecules encoding a coronavirus (e.g., SARS-CoV-2) spike protein S2 polypeptide (i.e., a polypeptide that includes a S2 domain, a variant thereof, or immunogenic fragments thereof, e.g., as described herein).

[001478] Among other things, the present application provides an insight that, in some embodiments, an RNA encoding an S2 polypeptide, or an immunogenic fragment or variant thereof (e.g., an immunogenic fragment described herein) can produce an improved immune response as compared to RNA encoding an appropriate reference antigen (e.g., as compared to RNA encoding a SARS-CoV-2 RBD, SARS-CoV-2 NTD or a full length SARS-CoV-2 S protein). In particular, in some embodiments, an RNA encoding an S2 polypeptide or an immunogenic fragment and/or variant thereof can produce a more broadly cross-neutralizing immune response (e.g., induce higher titers of antibodies that can bind and/or neutralize a greater number of SARS-CoV-2 strains or variants) as compared to an appropriate reference antigen or an RNA (e.g., mRNA) encoding an appropriate reference antigen.

[001479] Without wishing to be bound by theory, S2 polypeptides are highly conserved among panbetacoronaviruses, and also comprise broadly neutralizing epitopes. Thus, in some embodiments, an RNA encoding an S2 polypeptide, or an immunogenic fragment thereof, can elicit production of antibodes that can bind conserved neutralization eptiopes (e.g., epitopes that produce a neutralizing response), therefore resulting in an immune response that is more broadly cross-neutralizing (e.g., can induce a neutralization response against different betacoronaviruses, different sarbecoviruses, and/or different SARS-CoV-2 strains or varaints) as compared to RNA encoding an appropriate reference antigen (e.g, an RNA encoding a polypeptide that lacks the S2 domain and/or as compared to RNA that encodes a polypeptide comprising a full-length S protein). In some embodiments, an RNA encoding a polypeptide comprising the S2 polypeptide (and not the full length S protein), or an immunogenic fragment and/or variant thereof, can produce an improved immune response against the S2 polypeptide (or an immunogenic fragment and/or variant thereof) by increasing the accessibility of the S2 polypeptide (improved as compared to, e.g., an RNA encoding a full length S protein).

[001480] The S2 region of a coronavirus S protein (e.g., a SARS-CoV-2 S protein) is well characterized, and which region of the S protein corresponds to the S2 region would be well-understood by a person of skill in the art. See, e.g., Ravichandran, Supriya, et al. "Antibody signature induced by SARS-CoV-2 spike protein immunogens in rabbits." Science translational medicine 12.550 (2020): eabc3539, the contents of which is incorporated by reference herein in its entirety. In some embodiments, an S2 polypeptide (or an immunogenic fragment and/or variant thereof) contains a fusion peptide, and optionally other features necessary for membrane fusion with a host cell.

[001481] In some embodiments, an S2 polypeptide or lacks a transmembrane domain and is soluble. In some embodiments, an S2 polypeptide comprises amino acids 686-1213 of SEQ ID NO: 1 or a corresponding region of an S protein of a SARS-CoV-2 variant. In some embodiments, an S2 polypeptide comprises amino acids 686-1211 of SEQ ID NO: 1 or a corresponding region of a SARS-CoV-2 S protein of a SARS-CoV-2 variant. In some embodiments, an S2 polypeptide comprises amino acids 687-1206 of SEQ ID NO: 1 or a corresponding region of an S protein of a SARS-CoV-2 variant. In some embodiments, an S2 polypeptide comprises amino acids 687-1211 of SEQ ID NO: 1 or a corresponding region of a SARS-CoV-2 S protein of a SARS-CoV-2 variant.

[001482] In some embodiments, an S2 polypeptide comprises the following amino acid sequence: SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYH LMSFPQSAPHGWFLHVTYVPAQEKN FTTAPAICH DG KAH FPREG VFVSNGTHWFVTQRN FYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIKWP, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[001483] In some embodiments, an S2 polypeptide comprises the following amino acid sequence:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYH LMSFPQSAPHGWFLHVTYVPAQEKN FTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRN FYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[001484] In some embodiments, an S2 polypeptide comprises the following amino acid sequence:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCG KGYH LMSFPQSAPHGWFLHVTYVPAQEKN FTTAPAICH DGKAH FPREGVFVSNGTHWFVTQRN FYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[001485] In some embodiments, an S2 polypeptide comprises the following amino acid sequence:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRN FYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKY, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

[001486] In some embodiments, an RNA described herein comprises a nucleotide sequence that encodes a polypeptide comprising an immunogenic fragment of an S2 polypeptide. In some embodiments, an RNA encodes a polypeptide comprising an immunogenic fragment of an S2 polyeptide described in Zhou, Panpan, et al. "Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease." Immunity 56.3 (2023): 669-686, the contents of which are incorporated by reference herein in their entirety. In some embodiments, an immunogenic fragment of the S2 polypeptide comprises the stem-helix of an S2 polypeptide (e.g., LQPELDSFKEELDKYFKNHTSPDV) and/or the fusion peptide of an S2 polypeptide (e.g., PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD), which have previously been shown to be capable of inducing a broad and potent antibody response that is difficult for a coronavirus to escape. In some embodiments, an immunogenic fragment of an S2 polypeptide comprises the stem-helix of an S2 polypeptide and the fusion peptide of an S2 polypeptide, optionally connected via a flexible linker (e.g., a flexible linker described herein). In some embodiments, a polypeptide comprising a stem-helix and/or a fusion peptide of S2 can be membrane- tethered (e.g., by attaching a transmembrane domain described herein (e.g., C-terminal to the stem-helix and/or fusion peptide)). In some embodiments, a polypeptide comprising a stem-helix and/or of a fusion peptide of an S2 polypeptide can be secreted (e.g., by inclusion of a secretion signal (e.g., a secretion signal described herein, optionally position at the N-terminus of the polypeptide) and omission of a transmembrane domain). One example of an S2 stem helix fused to an S2 fusion peptide is a polypeptide comprising the following sequence: PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDGSGLQPELDSFKEELDKYFKNHTSPDV.

[001487] In some embodiments, an S2 polypeptide comprises one or more mutations that can stabilize the structure of the S2 polypeptide (e.g., stabilize the prefusion confirmation of the S2 polypeptide). Examples of such mutations are described e.g., in Bowen, John E., et al. "SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines," Science Immunology 7.78 (2022): eadfl421; Hsieh, Ching-Lin, et al. "Structure-based design of prefusion-stabilized SARS-CoV-2 spikes," Science 369.6510 (2020): 1501-1505; Olmedillas, Eduardo, et al. "Structure-based design of a highly stable, covalently-linked SARS- CoV-2 spike trimer with improved structural properties and immunogenicity" bioRxiv (2021): 2021-05; Halfmann, Peter J., et al. "Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses," EBioMedicine 86 (2022); Nuqui, Xandra, et al. "Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens," bioRxiv (2023): 2023-10; and Low, Jun Siong, et al. "ACE2- binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies," Science 377.6607 (2022): 735-742;, each of which is incorporated by reference herein in its entirety.

[001488] In some embodiments, a coronavirus S2 polypeptide (e.g., a SARS-CoV-2 S2 polypeptide) comprises substitutions corresponding to those shown to stabilize other coronavirus S2 polypeptides (e.g., other betacoronavirus S2 polypeptides, other sarbecovirus S2 polypeptides, MERS S2 polypeptide, and/or SARS-CoV-1 S2 polypeptides). E.g., in some embodiments, a SARS-CoV-2 S2 polypeptide described herein comprises one or more mutations at positions corresponding to one or more of the mutations described in Hsieh, Ching-Lin, et al. "Stabilized coronavirus spike stem elicits a broadly protective antibody" Cell reports 37.5 (2021), which describes mutations shown to stabilize a MERS S2 polypeptide, and the contents of which are incorporated by reference herein in their entirety. In some embodiments, a SARS-CoV-2 S2 polypeptide comprises one or more mutations corresponding to S375C, T859C, Q901M, A1020Q, H1058Y, or combinations thereof (mutations shown relative to SEQ ID NO: 1). In some embodiments a SARS-CoV-2 S polypeptide comprises mutations corresponding to S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L826C, L948C, or combinations thereof. In some embodiments, a SARS-CoV-2 S2 polypeptide comprises one or both pairs of mutations corresponding to I770C and A1015C, and/or V826C and L948C (mutations shown relative to SEQ ID NO: 1). In some embodiments, an S2 polypeptide comprises a sequence corresponding to that of constructs 21 and 22 listed in the below Table I.

[001489] In some embodiments, a SARS-CoV-2 S2 polypeptide comprises one or more mutations in hydrophobic regions that are accessible to solvent (e.g., which are normally buried but which are solvent accessible when S2 polypeptide is expressed without other regions of the S protein). In some embodiments, the one or more mutations introduce hydrophilic amino acids, and improve the solubility of the S2 polypeptide. [001490] In some embodiments, an S2 polypeptide (or an immunogenic fragment and/or variant thereof) comprises one or more mutations (e.g., one or more pairs of cysteine substitutions) that can form one or more disulfide bridges that increase stability of an S2 polypeptide (or an immunogenic fragment or variant thereof). [001491] Examples of mutations that can stabilize an S2 polypeptide (or immunogenic fragments and/or variants thereof) include a Pro substitution at one or both positions corresponding to amino acids 986 and 987 of SEQ ID NO: 1; a Pro substitution at one or more positions corresponding to amino acids 892, 899, 942, or combinations thereof of SEQ ID NO: 1 (optionally in combination with a Pro substitution at one or both positions corresponding to amino acids 986 and 987 of SEQ ID NO: 1); a Pro substitution at one or more positions corresponding to amino acids 817, 892, 899, 942, or combinations thereof of SEQ ID NO: 1 (optionally in combination with a Pro substitution at one or both positions corresponding to amino acids 986 and 987 of SEQ ID NO: 1); Cys mutations at positions corresponding to amino acids 707 and 883 of SEQ ID NO: 1 (optionally, in combination with Gly substitution at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1; and/or a Pro substitution at one or more positions corresponding to amino acids 892, 899, 941, 986, 987, or combinations thereof of SEQ ID NO: 1); and Cys substiutions at positions corresponding to amino acids 999 and 770 of SEQ ID NO: 1 (optionally in combination with Cys substiutions at positions corresponding to amino acids 707 and 883 of SEQ ID NO: 1; Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1; and/or a P substitution at one or more positions corresponding to amino acids 892, 899, 941, 986, 987, or combinations thereof of SEQ ID NO: 1). In some embodiments, mutations that stabilize an S2 polypeptide comprise mutations that remove an S2' protease site (e.g., Gly substitions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1 and/or as described in Halfmann et al.).

[001492] In some embodiments, a polypeptide comprising an S2 polypeptide, or an immunogenic fragment thereof, also comprises an RBD polypeptide. In some embodiments, the S2 polypeptide, or immunogenic fragment thereof, is attached to an RBD polypeptide via a flexible linker (e.g., a flexible linker as described herein). In some embodiments, the flexible linker comprises a protease cleavage site, so that the S2 polypeptide and the RBD polypeptide can be cleaved as they are transported to the cell surface and/or once they reach the cell surface. Suitable protease cleavage sites are known in the art, and include, e.g., a furin cleavage site. One example of a linker sequence comprising a furin cleavage site is a polypeptide comprising the following sequence: AGNRVRRSVG, or a variant thereof which can still be cleaved by a furin protease (e.g., human furin protease). [001493] In some embodiments, an S2 polypeptide and an RBD are connected via a rigid linker (e.g., a polypeptide comprising PA repeating, to a total length of 25-30 amino acids). In some embodiments an S2 polypeptide and an RBD are connected via a helical linker (e.g., a polypeptide comprising one of the following sequences: AEAAAKEAAAKA, AEAAAKEAAAKEAAAKA, AEAAAKEAAAKEAAAKEAAAKA, or AEAAAKEAAAKEAAAKEAAAKEAAAKA) .

[001494] In some embodiments, a polypeptide comprises an RBD and one or more immunogenic fragments of an S2 polypeptide (e.g., a stem helix and a fusion peptide of an S2 polypeptide (e.g., as described herein)). [001495] In some embodiments, a polypeptide comprising an S2 polypeptide (or one or more immunogenic fragments and/or variants thereof), and optionally an RBD polypeptide, comprises a transmembrane domain (e.g., an endogenous or exogenous transmembrane domain). Suitable transmembrane domains include, e.g., transmembrane domains described herein.

[001496] In some embodiments, a polypeptide comprising an S2 polypeptide (or an immogenic fragment and/or variant thereof) also comprises a trimerization domain. In some embodiments, a polypeptide comprising an S2 polypeptide, an RBD, and a protease cleavage site comprises two trimerization domains, which are configured such that, after cleavage of the protease cleavage site, a trimerization domain is present in the polypeptide comprising the S2 polypeptide and the polypeptide comprising the RBD.

[001497] Exemplary polypeptides comprising an S2 polypeptide are depicted in Figure 4 and are also provided in Table I.

[001498] In some embodiments, an mRNA construct encodes a polypeptide provided in Table I, below.

Table I: Sequences of Exemplary Polypeptides comprising an S2 polypeptide

[001499] The present example also describes an experiment for screening mRNA constructs encoding a polypeptide comprising an S2 polyeptpide for suitability as a vaccine. As an initial test for suitability, vaccine candidates are screened in vitro for expression (e.g., in a mammalian expression system). mRNA constructs that are tested include those depicted in Figure 4. Constructs that express well and/or which show acceptable stability in vitro are administered to subjects to test for immunogenicity (e.g., using experimental protocols known in the art or similar to those described herein). Example 2: Further Multi merization Domains

[001500] The present Example describes certain improved RNA (e.g., mRNA) constructs encoding a polypeptide comprising (i) a coronavirus (e.g., SARS-CoV-2) antigen (e.g., full length S protein, RBD polypeptide, NTD polypeptide, and/or S2 polypeptide), variants thereof, or immunogenic fragments thereof, e.g., as described herein), and (ii) multimerization domains. In some embodiments, the multimerization described in the present Example can induce highly multivalent oligomers (e.g., oligomers comprising 10 or more antigenic polypeptides). [001501] In some embodiments, an mRNA construct comprises a polypeptide comprising a multimerization domain that can induce multimerization of 10, 15, 20, 24, 25, 30, 35, 40, 45, 50, 55, 60, or more antigenic polypeptides.

[001502] In some embodiments, multimerization domains are selected so as to reduce an immune response generated against the multimerization domain itself. For example, in some embodiments, a relatively small multimerization domain is used (e.g., a multimerization domain comprising about 100 amino acids or less and/or a multimerization domain that comprises less than 20% of the total amino acids in a polypeptide). Additionally or alternatively, in some embodiments, a multimerization domain is used that forms an oligomer structure in which (i) the multimerization domain is not freely accessible in solution, and/or has reduced solvent accessibility as compared to a relevant comparator (e.g., other multimerization domains commonly used in commercial vaccines, e.g., a T4 fibritin domain); and/or (ii) the majority of antigen is freely accessible in solution and/or forms the majority of the solvent exposed surface area of an oligomer (e.g., 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, or 80% or more).

[001503] Suitable multimerization domains are known in the art, and include, e.g., those described in, Lainscek, Dusko, et al. "A nanoscaffolded spike-RBD vaccine provides protection against SARS-CoV-2 with minimal anti-scaffold response," Vaccines 9.5 (2021): 431; Joyce, M. Gordon, et al. "SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity," Cell reports 37.12 (2021); Joyce, M. Gordon, et al. "A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates," Science translational medicine 14.632 (2021): eabi5735; Wang, Chong, et al. "Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice." Antiviral research 140 (2017): 55-61; Johnston, Sara C., et al. "A SARS-CoV-2 spike ferritin nanoparticle vaccine is protective and promotes a strong immunological response in the cynomolgus macaque coronavirus disease 2019 (COVID-19) model," Vaccines 10.5 (2022): 717; Zhang, Baoshan, et al. "A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone," Scientific reports 10.1 (2020): 18149; Malhi, Harman, et al.

"Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge." Cell Reports Medicine 3.6 (2022); and WO2022043449A1, the contents of each of which is incorporated by reference herein in their entirety.

[001504] In some embodiments, an mRNA construct described herein comprises a multimization domain listed in Table II.

[001505] Table II: Exemplary Multimerization Domains

[001506] In some embodiments, a multimerization domain comprises a ferritin domain (e.g., as described in Table II). In some embodiments a multimerization domain comprises a ferritin domain that has been modified to reduced autoimmunity (e.g., as described in Kanekiyo, Masaru, et al. "Rational design of an Epstein-Barr virus vaccine targeting the receptor-binding site," Cell 162.5 (2015): 1090-1100, the contents of which are incorporated by reference herein in their entirety).

[001507] Exemplary polypeptides comprising a multimerization domain are provided in Tables III and VIII, below. In some embodiments, an mRNA construct described herein comprises a nucleotide sequence that encodes a polypeptide described in Table III or Table VIII.

Table III: Exemplary Polypeptides Comprising Multimerization Domains

Table VIII: Sequences of an Exemplary RNA Construct Encoding a Soluble Truncated-Si Polypeptide (aa 1-528 with (3-Annulus peptide (SP19-XBB.1.5- NTD-RBD528-(G4S)3 Linker-beta-Ann))

Example 3: mRNA Constructs For Production of Enveloped Viral Like Particles (VLPs)

[001508] The present Example describes compositions capable of producing enveloped VLPs that present one or more coronavirus (e.g., SARS-CoV-2) antigens (e.g., full length S protein, RBD polypeptide, NTD polypeptide, and/or S2 polypeptide, variants thereof, or immunogenic fragments thereof, e.g., as described herein) when administered to a subject.

[001509] Exemplary methods for producing VLPs include, e.g., those described in Zeltins, Andris. "Construction and characterization of virus-like particles: a review," Molecular biotechnology 53.1 (2013): 92-107; Yin, Shuanghui, et al. "Self-assembly of virus-like particles of porcine circovirus type 2 capsid protein expressed from Escherichia coli." Virology journal 7 (2010): 1-5; Wu, Pei-Ching, et al. "Characterization of porcine circovirus type 2 (PCV2) capsid particle assembly and its application to virus-like particle vaccine development," Applied microbiology and biotechnology 95 (2012): 1501-1507; Grgacic, Elizabeth VL, and David A. Anderson "Virus-like particles: passport to immune recognition." Methods 40.1 (2006): 60-65, the contents of each of which is incorporated by reference herein in its entirety. The present disclosure describes new constructs and strategies for producing antigen-presenting VLPs in a subject (in particular coronavirus antigen presenting VLPs, which can, in some embodiments, be provided in mRNA compositions, and which can provide certain advantages as compared to previous approaches).

[001510] In some embodiments, compositions capable of forming VLPs comprise two or more mRNA molecules: (i) one or more mRNA molecules, each of which encodes a polypeptide comprising a coronavirus antigen and (ii) one or more mRNA molecules, each of which encodes a polypeptide that, separately or together with an another polypeptide encoded by an mRNA molecule in the composition, can induce formation of a VLP in vivo. For example, in some embodiments, a composition comprises one or more mRNA constructs described herein, and one or more mRNA constructs, each of which encodes a viral polypeptide that can induce formation of a VLP. In some embodiments, a composition comprises: (i) one or more mRNA constructs, each encoding a coronavirus antigen, and (ii) an mRNA encoding a SARS-CoV-2 M polypeptide and an mRNA encoding a SARS- CoV-2 E polypeptide (e.g., as described in Lu, Jing, et al. "A COVID-19 mRNA vaccine encoding SARS-CoV-2 viruslike particles induces a strong antiviral-like immune response in mice." Cell research 30.10 (2020): 936-939. Lu, Jing, et al. "A COVID-19 mRNA vaccine encoding SARS-CoV-2 virus-like particles induces a strong antiviral-like immune response in mice." Cell research 30.10 (2020): 936-939, the contents of which are incorporated by reference in their entirety. In some embodiments, the mRNA encoding a SARS-CoV-2 M protein and the mRNA encoding a SARS-CoV-2 E protein are present at a molar ratio of 1:1. In some embodiments, the molar ratio of: (i) the one or more mRNA constructs encoding a coronavirus antigen, (ii) the mRNA encoding a SARS-CoV-2 M protein, and (iii) the mRNA encoding a SARS-CoV-2 E protein is l-5:l-5:l-5; 1:5:5, 1:4:4; 1:3:3; 1:2:2; or 1:1:1. [001511] Alternatively, in some embodiments, an mRNA construct described herein encodes a polypeptide comprising: (i) a coronavirus antigen (e.g., a full-length S protein, an RBD polypeptide, an NTD polypeptide, and/or an S2 polypeptide, immunogenic fragments thereof, and/or variants thereof), and (ii) one or more sequences that, together or separately, can induce formation of a VLP when the polypeptide is expressed in a subject.

[001512] In some embodiments, the present disclosure provides the insight that a VLP can be produced that comprises multiple coronavirus antigens (e.g., antigens of different SARS-CoV-2 variants or stains or different antigens of the same SARS-CoV-2 variant or strain). In some embodiments, an mRNA composition capable of forming VLPs when administered to a subject comprises two or more mRNA constructs, each encoding a coronavirus antigen, for example:

• two or more mRNA constructs, each encoding a coronavirus antigen (e.g., RBD polypeptide, NTD polypeptide, or full length S protein) of a different coronavirus (e.g., different betacoronaviruses; different sarbecoviruses; a SARS-CoV-2 virus and a SARS-CoV-1 virus, or a SARS-CoV-2 virus and a MERS virus); or

• two or more mRNA constructs each encoding an antigen (e.g., an NTD polypeptide, RBD polypeptide, or full length S protein) of a different coronavirus (e.g., SARS-CoV-2) strain or variant.

[001513] In some embodiments, a polypeptide comprises an endosomal sorting complex required for transport (ESCRT)- and ALG-2-interacting protein X (ALIX) binding region (collectively referred to as EABR), e.g., as described in Hoffmann, Magnus AG, et al. "ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines." Cell 186.11 (2023): 2380-2391, the contents of which are incorporated by reference herein in their entirety. In some embodiments, an EABR sequence comprises FNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLLAKIFELEKKTETAAHSLP. In some embodiments, a polypeptide comprising an EABR sequence also comprises an EPM sequence (e.g., ALPGNPDHREMGETLPEEVGEYRQPSGGSVPVSPGPPSGLEPTSSSSPY). In some mbodiments, an EABR sequence comprises LQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ. In some embodiments, a polypeptide comprising an EABR sequence comprises a transmembrane domain (e.g., a transmembrane of a SARS-CoV-2 S protein (e.g., as described herein, optionally with a C-terminal proximal sequence). An exemplary polypeptide comprising a SARS-CoV-2 antigen and an EABR sequence is shown in Figure 6, and two exemplary polypeptide sequences are provided in Table IV.

[001514] In some embodiments, a sequence capable of inducing vesicle formation when attached to a polypeptide comprising a coronavirus antigen is a sequence that comprises a VSV-G transmembrane domain. The present application provides the first use of VSV-G sequences for vaccination against any disease. In particular, VSV-G transmembrane domains have previously been used to generate vesicles that can be used for cargo delivery. The present disclosure is the first to recogonize that vesicles produced using a VSV-G transmembrane domain can be used for generating an immune response (e.g., by attaching a VSV-G transmembrane domain to an antigen, which results in the production of a vesicle that displays the antigen to the extravesicle environment, allowing for an immune response to be generated). In some embodiments, a polypeptide comprising a VSV-G polypeptide sequence also includes a trimerization domain.

[001515] In some embodiments, a VSV-G transmembrane domain includes a short membrane proximal sequence (e.g., a signal portion of a membrane proximal ectodomain (e.g., a polypeptide comprising: IELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK or FEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCI, variants thereof, or fragments thereof)). In some embodiments, a VSV-G transmembrane domain (with optional membrane proximal sequence) is at the C-terminus of a polypeptide.

[001516] In some embodiments, a C-terminal region of a SARS-CoV-2 S protein (e.g., a polypeptide comprising a sequence that corresponds to amino acids 1237-1245 of SEQ ID NO: 1; or MTSCCSCLKGCCSCGSCC). In some embodiments, a polypeptide comprises a short stretch of a membrane proximal sequence of the SARS-CoV-2 S protein (e.g., an amino acid sequence corresponding to residues 1209- 1217 of SEQ ID NO: 1), C-terminal to (e.g., immediately C-terminal to, or connected by a linker to) a transmembrane domain (e.g., a transmembrane domain of a SARS-CoV-2 S protein).

[001517] The present application is also the first to recognize and demonstrate that certain SARS-CoV-2 components can be used directly to a coronavirus antigen and used to induce vesicle formation and antigen presentation. Without wishing to be limited by theory, such constructs provide the advantage of reducing the number of mRNA constructs that need to be administered to a subject, which in turn reduces the amount of RNA that needs to be administered to a subject. Reducing the amount of mRNA encoding a coronavirus antigen can be advantageous, e.g., because it can reduce the severity and/or incidence of undesired side-effects, and also allow for the inclusion of additional mRNA constructs encoding additional antigens (SARS-CoV-2 or to other respiratory disase (e.g., influenza and/or RSV).

[001518] In some embodiments, a polypeptide comprising a peptide derived from VP40 TSG101 and p6 Alix (e.g., VILPTAPPEYMEA and (DKELYPLTSLRSLFGN or TQNLYPDLSEIKKEYNVKEKDQVEDLNLDSLWE), optionally connected by a flexible linker (e.g., VILPTAPPEYMEAGSGSGSDKELYPLTSLRSLFGN) is capable of inducing VLP formation. In some embodiments, a polypeptide comprising a minimal TSG 101 and Alix motifs, optionally connected via flexible linkers (e.g., GSGSGSPTAPPEYGSGSGSLYPLTSLRSLGSGSGSPTAPGSGSGSLYPDLNLDSLGSGSGSPSAP) is capable of inducing VLP formation. Examples of a polypeptide comprising a SARS-CoV-2 antigen and comprising a C-terminal VP40+TSG101 + p6 Alix sequences are provided in Table IV, below.

[001519] In some embodiments, portions of a capsid protein of Porcine circovirus 2 (PVC-2) can be attached to a polypeptide comprising a coronavirus antigen (e.g., as as depicted in Figure 5). In some embodiments, an mRNA construct described herein encodes a polypeptide depicted in Figure 5. Exemplary sequences of a portion of a PVC-2 capsid protein that can induce formation of a VLP are provided in Table V, below.

[001520] Exemplary polpyetide sequences comprising an RBD, full length S polypeptide, an M polypeptide, and E polypeptide are provided in Table IV, below. Also provided in Table IV are exemplary polypeptides comprising a SARS-CoV-2 antigen and a polypeptide sequence, and which can induce formation of a VLP displaying a SARS-CoV-2 antigen. In some embodiments, compositions described herein comprise an mRNA construct encoding a coronavirus antigen, and mRNA construct encoding a polypeptide comprising an M polypeptide, and an mRNA construct encoding a polypeptide that encodes an E polypeptide, each provided in Table IV. In some embodiemnts an mRNA construct described herein encodes a polypeptide comprising a sequence provided in Table IV.

[001521] Table IV: Exemplary Polypeptides For Use in Generating Viral Like Particles (VLPs) Presenting SARS- CoV-2 Antigens

Table V: Exemplary Constructs Comprising a PVC-2 Capsid Polypeptide

Table XI: Sequences of an Exemplary RNA Construct Encoding a Soluble Truncated-Si Polypeptide with EABR(aa 1-528) (SP19-XBB.1.5-NTD-RBD528- (G4S)4 Linker-TM(deltal9)-Linker-EABR)

Table XII: Sequences of an Exemplary RNA Encoding a Polypeptide Comprising a Membrane Anchored SI Polypeptide (SP25(HSV-1 gD_RG)-(NTD- RBD)i4-528-((G₄S)3)-TMD(VSV-G_mid_Q427 ectodomain)

Table XIII: Sequences of an Exemplary RNA Encoding a Polypeptide Comprising a Membrane Anchored SI Polypeptide (SP25(HSV-1 gD_RG)-(NTD- RBD)i4-528-((G₄S)₃)-TM D(VSV-G_long ectodomain)

Table XIV: Sequences of an Exemplary RNA Construct Encoding a Membrane-Anchored RBD and Lacking a Soluble Trimerization Domain (SP19- RBD(XBB.1.5)-GS_Linker-TM(VSV-G))

Table XV: Sequences of an Exemplary RNA Construct Encoding a Membrane-Anchored RBD and Lacking a Soluble Trimerization Domain (SP19- RBD(XBB.1.5)-GS_Linker-TM(VSV-G))

Table XVI: Sequences of an Exemplary RNA Encoding a Polypeptide Comprising a Membrane Anchored RBD Polypeptide (SP25(HSV-1 gD_RG)-RBD327- 528-(G4S)4_Linker-TMD(VSV-G_long ectodomain)

Table XVII: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated-Si Polypeptide (aa 1-528 without Fibritin Domain (SP19-XBB.1.5-NTD-RBD528-(G4S)3_Linker-VSV-G-TMD(short))

Table XVIII: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated-Si Polypeptide (aa 1-541 without Fibritin Domain (SP19-XBB.1.5-NTD-RBD541-(G4S)3_ Linker-VSV-G-TMD(short))

Table XXI: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored RBD Polypeptide (without Fibritin Domain (SP25 GD_HHV1K -XBB.1.5-RBD-GS_Linker-TM(VSV-G_short))

Table XXII: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored RBD Polypeptide (without Fibritin Domain (SP25 GD_HHV1K -XBB.1.5-RBD-GS_Linker-TM(VSV-G_mid_Q427))

Table XXIII: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored RBD Polypeptide (without Fibritin Domain (GD_HHV1K- XBB.1.5-RBD-GS_Linker-TM(VSV-G_mid_F440))

Table XXIV: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated SI Domain Polypeptide (without Fibritin Domain (GD_HHVlK-XBB.1.5-NTD-RBD528-GS_Linker-TM(VSV-G_short))

Table XXV: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated SI Domain Polypeptide (without Fibritin Domain (SP25 GD_HHVlK-XBB.1.5-NTD-RBD528-GS_Linker-TM(VSV-G_mid_F440))

Table XXVI: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated SI Domain Polypeptide (without Fibritin Domain (SP25 GD_HHVlK-XBB.1.5-NTD-RBD528-GS_Linker-TM(VSV-G_long)

Table XXVII: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated SI Domain Polypeptide (without Fibritin Domain (SP25 GD_HHVlK-XBB.1.5-NTD-RBD528-(G4S)2-TM(VSV-G_mid_Q427))

Table XXVIII: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated SI Domain Polypeptide (without Fibritin Domain (SP25 GD_HHVlK-XBB.1.5-NTD-RBD528-(G4S)l-TM(VSV-G_mid_Q427))

Table XXIV: Sequences of an Exemplary RNA Construct Encoding a Membrane Anchored Truncated SI Domain Polypeptide (without Fibritin Domain (SP19-XBB.1.5-NTD-RBD541-(G4S)3_Linker-VSV-G-TMD(short))

Table VII: Sequences of an Exemplary RNA Construct Encoding a Trimerized, Membrane-Anchored RBD (SP19-XBB.1.5_RBD-GS_Linker-Fibritin_Short-GS_Linker-

TM(deltal9))

Example 5: In Vitro Expression of Soluble S2 Polypeptides Comprising Various Stabilizing Mutations [001525] The present Example provides data characterizing the in vitro expression of various polypeptides that comprise an S2 polypeptide comprising one or more stabilizing mutations but that do not comprise a transmembrane domain. In particular, the present Example provides in vitro data characterizing the expression of RNA comprising a nucleotide sequence encoding one of the below listed SARS-CoV-2 antigens. For each of the mutations listed below, mutation positions are indicated relative to SEQ ID NO: 1.

• Construct 1: Full length S protein, comprising K986P and V987P mutations

• Construct 2: S2 polypeptide comprising K986P and V987P mutations and comprising a fibritin domain (RNA encoding SEQ ID NO: 183 in the present Example);

• Construct 3: S2 polypeptide comprising A892P, A899P, A942P, K986P, and V987P mutations and comprising a fibritin domain (RNA encoding SEQ ID NO: 184 in the present Example);

• Construct 4: S2 polypeptide comprising A892P, A899P, A942P, K986P, and V987P mutations and Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1 and comprising a fibritin domain (RNA encoding SEQ ID NO: 185 in the present Example);

• Construct 5: S2 polypeptide comprising mutations Y707C, T883C, A892P, A899P, A942P, and V987P and Gly substitutions at positions 814 and 815 with a fibritin domain (RNA encoding SEQ ID NO: 442 in the present Example);

• Construct 6: S2 polypeptide comprising mutations A892P, A899P, A942P, V987P, V707C, T883C, F970C, G999C, and Gly substitutions at positions 814 and 815;

• Construct 7: S2 polypeptide comprising mutations S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, K986P, and V987P and with a fibritin domain (RNA encoding SEQ ID NO: 443 in the present Example);

• Construct 8: S2 polypeptide comprising mutations F817P, A892P, A899P, A942P, K986P, V987P, F855S, L861E, L864D, V976D, and L984Q and comprising a fibritin domain (an RNA encoding SEQ ID NO: 195 in the present Example).

[001526] RNA was transfected into cell culture. A sample comprising cells not transfected with RNA was also included as a negative control.

[001527] After incubating an appropriate amount of time, intracellular staining was performed using fluorescently labeled antibodies that bind different regions of the S2 domain.

[001528] Polypeptide expression as measured using a fluorescently labeled antibody that binds S2 is shown in Figs. 7(A)-(B). As shown in Figs. 7(A)-(B), all RNA molecules tested produced detectable expression of an S2 polypeptide. Fig. 7(A) shows that all RNA tested produced a comparable percent of cells expressing the S2 polypeptide. Fig. 7(B) shows that, among the constructs tested, S2 polypeptides comprising (i) mutations K986P and V987P (Construct 2), and (ii) mutations Y707C, T883C, A892P, A899P, A942P, and V987P and Gly substitutions at positions corresponding to amino acids 814 and 815 of SEQ ID NO: 1 (Construct 5) exhibited the highest level of S2 expression, with both Construct 2 and Construct 5 showing increased expression as compared to RNA encoding a full length S protein (Construct 1). Construct 6 (comprising A892P, A899P, A942P, V987P, V707C, T883C, F970C, G999C mutations, and Gly substitutions at positions 814 and 815) also showed increased expression as compared to RNA encoding a full length S protein.

[001529] Intracellular staining was also performed using three different antibodies that bind the stem-helix region of the S2 polypeptide, and which previously had been shown to be capable of neutralizing the SARS-CoV-2 virus (antibodies SH nAbl-3). Results are shown in Figs. 8(A)-(C). As shown, each of the RNA molecules tested exhibited increased signal as compared to RNA encoding a full length S protein, demonstrating that the stem-helix region has increased accessibility and/or expression in the encoded polypeptides. As discussed elsewhere in the present disclosure, without wishing to be bound by theory, increased accessibility of the stem-helix peptide may increase the likelihood of inducing production of stem-helix specific anibodies in a subject. The stem helix is highly conserved and comprises neutralizing epitopes, and therefore constructs that offer improved stem helix accessibility may be more likely to induce an improved immune response, including, e.g., increased titers of neutralizing antibodies and increased cross-neutralization (e.g., as compared to a composition that delivers a full length S protein). Of the RNA molecules tested, Construct 2 (encoding an S2 polypeptide comprising mutations K986P and V987P) and Construct 7 (encoding an S2 polypeptide comprising mutations S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, K986P, and V987P) produced the highest stem helix signal. The stem helix region appears to be especially accessible in Construct 7, given that this construct produced one of the lowest levels of expression when probing with an antibody that binds the S2 polypeptide (see Fig. 7(B)) and the highest signal when probing with stem helix specific antibodies (see Figs. 8(A)-(C)).

[001530] Cells were also probed using three different antibodies that bind the fusion peptide of the S2 polypeptide (FP nAbl-3). Results are shown in Figs. 9(A)-(C). As shown, unlike the antibodies that bind the S2 polypeptide and stem helix peptide, in which all constructs showed significant fluorescent signal, fusion peptide signal (a measure of accessibility and expression level) was found to vary greatly among the constructs tested. Among those tested, Construct 2 (encoding an S2 polypeptide comprising mutations K986P and V987P) and Construct 7 (encoding an S2 polypeptide comprising mutations S735C, T859C, Q901M, A1020Q, H1058Y, I770C, A1015C, V826C, L948C, K986P, and V987P) exhibited the highest signal, consistent with the stem helix results. Similar to the stem helix region, the fusion peptide also appears to be especially accessible in Construct 7, given that this construct produced one of the lowest levels of expression when probing with an antibody that binds the S2 polypeptide (see Fig. 7(B)) and the highest signal when probing with stem helix specific antibodies (see Figs. 9(A)-(C)). Remarkably, Construct 1 (an RNA encoding a full length S protein) showed no fusion peptide signal, indicating that this region of the S protein is not readily accessible in the context of the full length S protein. Constructs 2 and 7, in contrast, exhibited strong fusion peptide signal, indicating that the fusion peptide is much more accessible in these constructs as compared to the full length S protein. As discussed elsewhere in the present disclosure, without wishing to be bound by theory, increased fusion peptide accessibility may result in an increased immune response against the fusion peptide region of the S protein (e.g., as compared to a composition that delivers a full length S protein). Given that this region comprises neutralizing epitopes and is highly conserved, induction of antibodies that bind the fusion peptide may result in an improved immune response, including, e.g., increased neutralization titers and/or improved cross-neutralization. Given the increased accessibility of the stem helix peptide and the fusion peptide in Constructs 2 and 7, both of these constructs may induce a stem helix and fusion peptide specific immune reaction in subjects, and therefore may result in an improved immune response as compared to compositions that deliver a full length S protein.

Example 6: In Vitro Expression of RBD-S2 Polypeptides

[001531] The present Example provides in vitro expression data for RNA constructs encoding a polypeptide comprising an RBD and either an S2 polypeptide or one or more fragments of the S2 polypeptide (in particular a stem helix and fusion peptide region of the S2 domain). In the present Example, S2 polypeptides and fragments thereof are of SARS-CoV-2 origin.

[001532] A list of the polypeptides encoded by the RNA molecules tested herein is provided below. The mutations listed below are indicated relative to SEQ ID NO: 1.

• Construct 1: Full length S protein comprising K986P and V987P mutations.

• Construct 2: An S2 polypeptide comprising K986P and V987P mutations.

• Construct 3: RBD of a SARS-CoV-2 S protein, attached to a transmembrane domain and a fibritin trimerization domain.

• Construct 4: A polypeptide comprising an S2 polypeptide, an RBD, two fibritin domains, and comprising a transmembrane domain (RNA encoding SEQ ID NO: 188 in the present Example).

• Construct 5: A polypeptide comprising an S2 polypeptide, an RBD, a fibritin domain, and comprising a transmembrane domain (RNA encoding SEQ ID NO: 444 in the present Example).

• Construct 6: A polypeptide comprising an S2 polypeptide, an RBD, and a transmembrane domain (RNA encoding SEQ ID NO: 445 in the present Example).

• Construct 7: A polypeptide comprising a stem helix (SH) peptide, a fusion peptide (FP), an RBD, a transmembrane domain and a fibritin domain, where the SH and FP are N-terminal to the RBD (RNA encoding SEQ ID NO: 190 in the present Example);

• Construct 8: A polypeptide comprising a stem helix (SH) peptide, a fusion peptide (FP), an RBD, a fibritin domain, and a transmembrane domain, where the SH and FP are C-terminal to the RBD (RNA encoding SEQ ID NO: 191 in the present Example);

[001533] RNA encoding one of the above listed polypeptides was transfected into cells. After incubating an appropriate amount of time, cells were probed with appropriate agents to measure cell surface and intracellular signal (a result of a combination of expression and accessibility) of RBD, S2 polypeptide, stem helix, and fusion peptide regions of the S2 polypeptide.

[001534] Cell surface RBD signal was measured using fluorescently labeled ACE2, and results are shown in Fig. 11. As expected, constructs Construct 1 (encoding a full length S protein), Construct 3 (encoding a polypeptide comprising a transmembrane domain and an RBD, Construct 6, and Construct 8 (comprising an RBD, SH, FP, and transmembrane domain) each showed high surface level signal of RBD. Also as expected, Construct 2, which lacks an RBD, also exhibited low ACE2 signal. Interestingly, Construct 6 exhibited increased cell surface ACE2 signal as compared to Constructs 4 and 5 (which have a similar design as Construct 6, but which comprise one or two fibritin domains), indicating that exclusion of a fibritin domain can improve cell surface expression.

[001535] Cell surface and intracellular S2 polypeptide signal was measured using a fluorescently labeled antibody that binds the S2 polypeptide. Results are provided in Figs. 12(A)-(B). As expected, Construct 3 (which lacks an S2 polypeptide) displayed low cell surface and intracellular S2 polypeptide signal (see Figs. 12(A) and (B)). Constructs 2 and 4-8 all exhibited intracellular S2 polypeptide signal that was higher than that of Construct 1 (encoding a full length S protein; See Fig. 12(A)). As expected, Construct 2 (which lacks a transmembrane domain) exhibited low cell surface S2 signal. Constructs 4-6 (which include a transmembrane domain, but are configured such that, upon cleavage, the S2 domain is not linked to the transmembrane domain and is soluble) exhibited low cell surface S2 signal, indicating that the furin protease site was being cleaved. Constructs 7 and 8, exhibited significant S2 cell surface signal. Construct 8, in particular, exhibited strong S2 signal, which was higher than that observed by Construct 1 (which encoded a full length S polypeptide). The observation that the S2 cell surface signal induced by Construct 8 was higher than that induced by Construct 7 (as shown in Fig. 12(B)) was surprising, given that intracellular S2 signal was higher for Construct 7 than Construct 8 (see Fig. 12(A)). Without wishing to be bound by theory, one potential explanation for this observation is that a greater portion of an encoded polypeptide reaches and/or that SH and/or FP is more accessible at the cell surface membrane when an RBD is N-terminal to the SH and FP sequences (as in Construct 8).

[001536] Cells were also stained for cell surface and intracellular expression of the stem helix (SH) region of the S2 polypeptide, using an antibody that binds the stem helix region and which had previously been shown to be capable of neutralizing a SARS-CoV-2 virus. Once again, as expected, Construct 3 (which lacks regions of the S2 polypeptide) exhibited low intracellular and cell surface SH signal (see Figs. 13(A) and (B)). The rest of the constructs tested displayed increased intracellular SH signal as compared to Construct 1 (encoding a full length S protein), indicating that SH is more highly expressed and/or more accessible in each these constructs.

[001537] Also as expected, low cell surface SH signal was observed for the construct lacking a transmembrane domain (Construct 2). Constructs 4, 5, and 6, which comprise a transmembrane domain, but are configured such that, upon cleavage of the internal furin protease site, the transmembrane domain is not linked to the S2 domain, also exhibited low cell surface SH signal. This result indicates that the furin protease linker is being cleaved, as intended. See Fig. 13(B)). For Constructs 7 and 8, cell surface SH signal was observed, with Construct 8 exhibiting particularly strong SH signal (close to double that of full length S protein). Once again, intracellular signal was higher for Construct 7 as compared to Construct 8, but the opposite was observed for cell surface expression, which is consistent with the SH peptide being more accessible and/or more of the polypeptide reaching the cell surface when an RBD is N-terminal to SH and FP peptides.

[001538] Lastly, intracellular and cell surface signal for the fusion peptide (FP) of the S2 domain was probed using an antibody that had previously been shown to bind this region and also to be capable of neutralizing a SARS-CoV-2 virus. Results are provided in Figs. 14(A) and (B). As expected, Construct 3, which lacks an FP, displayed very low intracellular and cell surface signal. For Construct 1 (encoding a full length S protein), unlike the SH signal, and consistent with the results reported in Example 5 of the present application, very low intracellular and cell surface FP signal was observed (see Figs. 14(A) and (B)). Each of Constructs 2 and 4-8, in contrast, showed detectable intracellular FP signal (see Fig. 14(A)), indicating that the FP is more accessible in each of these constructs as compared to the full length S protein. As expected, low cell surface FP signal was observed for Construct 2, which lacks a transmembrane domain, and 4-6, which comprise a transmembrane domain, but are configured such that, upon cleavage of an internal furin cleavage site, the transmembrane domain is not linked to the S2 polypeptide. This observation is again consistent with the furin protease site being cleaved Constructs 4-6. Constructs 7 and 8 both displayed high cell surface FP signal, with Construct 8 in particular showing very high signal. This is again consistent with a greater portion of polypeptide reaching the cell surface, and/or increased FP accessibility at the cell surface, when RBD is N-terminal to the SH and FP peptides.

[001539] The data provided in the present Example demonstrates that constructs described herein can induce detectable expression of SARS-CoV-2 antigens when transfected into cells. In particular, it demonstrates that constructs provided herein can produce detectable expression of the S2 polypeptide, and the SH and FP regions of the S2 polypeptide. FP signal is especially increased in constructs described herein as compared to constructs that deliver a full length S protein. SH signal was also increased as compared to constructs that deliver a full length S protein. Without wishing to be bound by theory, the SH and FP regions of the S2 polypeptide are highly conserved and also include neutralizing epitopes. Thus, compositions that can induce an immune response directed to this region may be more likely to result in an improved immune response, including, e.g,. higher neutralizing titers, and/or increased cross-neutralization as compared to compositions that deliver an antigen where the SH and/or FP regions are less accessible (including, e.g., compositions that deliver a full length S protein).

[001540] Example 7: Immune Responses Induced by RNA Encoding S2-RBD and SH-FP-RBD Polypeptides in Vaccine Naive Mice

[001541] The present Example describes an experiment in which RBD-S2 and RBD-SH-FP constructs described herein (i.e., RNA encoding a polypeptide comprising (i) an RBD and S2 polypeptide, or (ii) an RBD and stem helix (SH) and fusion peptide (FP) peptides) were administered to vaccine naive mice. Among other things, the data provided in the present Example demonstrates that constructs described herein that include an SH, SP, and RBD region can result in increased neutralization titers as compared to RNA encoding a full length S protein. The data provided in the present Example also demonstrates that RNA encoding an S2 polypeptide and an RBD can result in improved cross neutralization as compared to RNA encoding a full length S protein.

[001542] The RNA constructs tested in the present Example are listed below.

• Construct 1: Encoding a full length S protein (XBB.1.5 adapted).

• Construct 2: Encoding a polypeptide comprising an RBD, a SARS-CoV-2 transmembrane domain, and a fibritin domain, where the RBD is from an S protein of an XBB.1.5 SARS-CoV-2 variant.

• Construct 3: Encoding a a polypeptide comprising an S2 domain of a SARS-CoV-2 Wuhan strain and an RBD of an XBB.1.5 strain, a fibritin domain linked to each of the S2 domain and the RBD, a transmembrane domain, and an internal linker sequence comprising a furin protease site connecting the RBD and the S2 domain (RNA encoding SEQ ID NO: 188 in the present Example).

• Construct 4: Encoding a polypeptide comprising an SH, FP, and RBD (XBB.1.5-adapted) and a transmembrane domain of a SARS-CoV-2 S protein, where the SH and FP are N-terminal to the RBD (RNA endoing SEQ ID NO: 190 in the present Example).

• Construct 5: Encoding a polypeptide comprising an SH, FP, and RBD (XBB.l.S-adapted) and a transmembrane domain of a SARS-CoV-2 S protein, where the SH and FP are C-terminal to the RBD (RNA endoing SEQ ID NO: 191 in the present Example).

[001543] The table in Fig. 15 summarizes the experimental protocol followed in the present Example. In brief, vaccine naive mice were administered two 1 μg doses of LNP-formulated RNA, where the two doses were administered 21 days apart. Sera sample were collected 7, 14, 21, and 34 days after administering the first dose of RNA and titers of neutralizing antibodies against a Wuhan SARS-CoV-2 strain, XBB.1.5 SARS-CoV-2 strain, and BA.4/5 strain were measured using a pseudovirus neutralization assay. At day 34, mice final sera samples were collected and mice were sacrificed.

[001544] Neutralization titers at days 7, 14, 21, and 34 are provided in Figs. 16(A)-(D), respectively. As shown in Fig. 16(D), by day 34, neutralization titers induced by Construct 5 against both an XBB.1.5-adapted and a Wuhan adapted pseudovirus had increased to be ~1.5 times higher than those induced by Construct 1 (encoding a full-length S protein). By day 34, Construct 3 (encoding a polypeptide comprising an S polyeptide of a Wuhan strain and an RBD of an XBB.l.S-adapted strain), had induced neutralization titers against a Wuhan strain that were close to double those induced by Construct 1 (see Fig. 16(D)), thus demonstrating that RNA described herein can result in improved cross-neutralization as compared to compositions that deliver a full length S protein of a SARS-CoV-2 virus.

[001545] Antibody titers against the RBD of the XBB.1.5 S protein and the RBD of the Wuhan S protein were also measured in sera samples collected at day 34. Results are shown in Figs. 17(A) and (B). As shown, each of Constructs 4 and 5 produced higher antibody titers against both a Wuhan and an XBB.1.5 RBD as compared to Construct 1. Non-neutralizing antibodies have been shown to be capable of providing a beneficial effect in subjects. See, e.g., Izadi, Arman, and Pontus Nordenfelt. "Protective non-neutralizing SARS-CoV-2 monoclonal antibodies." Trends in Immunology 45.8 (2024): 609-624, the contents of which are incorporated by reference herein in their entirety.

Example 8: VLP Formation and (3-Annulus tagged Polypeptide Expression In Vitro and Immunogenecity

[001546] The present Example provides initial data characterizing the ability of compositions described herein to induce VLP formation and induce an immune response in mice. Also provided in the present Example is data demonstrating the ability of RNA described herein to induce expression of polypeptides comprising a SARS-CoV-2 antigen and a [3-Annulus multimerization domain.

[001547] Fig. 18(A) provides general schematics of the constructs characterized in the present Example. In short, constructs were tested comprising (i) an RBD or a truncated SI domain (in the present Example, comprising a region corresponding to amino acids 1-528 or 1-541 of SEQ ID NO: 1, where the endogenous secretory signal peptide has been replaced with an SP25-GD-HHV1K secretory signal peptide)), and (ii) a VSV-G transmembrane domain or a p-annulus peptide domain, where the RBD or the truncated SI domain are connected to the VSV-G transmembrane domain or [3-annulus peptide domain via a linker (C'L") in Fig. 18(A)). [001548] In the present Example, RNA was transfected into HEK 293T/17 cells. Samples were then centrifuged and supernatant collected. Sandwich-ELISA was performed using an antibody that binds the S protein and hACE-2-Fc as a capture/detection pair, so as to measure RBD signal. Without wishing to be bound by theory, VLPs are expected to remain in the supernatant after centrifugation. Accordingly, increased RBD signal in the supernatant in cell cultures transfected with RNA encoding a polypeptide comprising a transmembrane domain is consistent with increased VLP formation. Lack of RBD signal in the supernatant and positive RBD signal at the cell surface is indicative of a lack of VLP formation.

[001549] RBD supernatant signal for the constructs listed below is provided in Fig. 18(C).

. 3609 (XBB.1.5-RBD)

. 3618 (RBD_TM VSV-G_Long)

. 3619 (RBD_TM VSV-G_short)

• 3732 (Truncated SI domain)

• 3970 (Truncated SI domain_ VSV-GJong)

• 4050 (Truncated SI domain_ VSV-G_short)

• 4012 (Truncated SI domain_ Beta Ann)

[001550] RNA encoding a polypeptide comprising a truncated SI domain and a p-annulus peptide produced the highest supernatant signal. This result was expected, as this RNA was the only one tested that encoding a polypeptide that lacked a transmembrane domain. Of the RNAs encoding polypeptides that comprised a transmembrane domain, all polypeptides comprising a VSV-G transmembrane domain (3618, 3619, 3970, and 4050) resulted in increased supernatant RBD signal as compared to RNA encoding a SARS-CoV-2 antigen linked to a SARS-CoV-2 transmembrane domain (3609 and 3732; a SARS-CoV-2 transmembrane domain is not expected to induce VLP formation). This observation indicates that RNA described herein encoding a polypeptide comprising a SARS-CoV-2 antigen and a VSV-G transmembrane domains may be capable of inducing VLP formation when transfected into a cell. 3618 produced especially high supernatant signal, indicating that the VSV-GJong transmembrane domain may be especially effective at promoting VLP formation.

[001551] Immunogenecity of the 3619 was also tested in mice. Mice were administered two doses of 3619 or 2303 (encoding a full length S protein). Sera samples were collected 7, 14, 21, 28, and 35 days after administering a first dose. Results are provided in Figs. 19(A)-(F). As shown, asingle dose of RBD-VSV vaccine antigen (3619) showed comparable nAb GMTs (between 80-160), 7-21 days post immunization. 7 days after 2^nd dose 3619 produced a 1.5-fold increased titer compared to 2303. Titers for both compositions decreased 14 days post-boost, but 3619 resulted in less of a decrease (antibody titers were found to be more stable).

Characterizing the Effect of Different VSV-G Transmembrane Domains on VLP Formation

[001552] The effect of different VSV-G transmembrane domains (in particular, the effect of including different membrane proximal sequences) on VLP formation was tested. Cell surface expression and supernatant expression was measured using the same ELISA assay described above in the present Example as a measure of VLP formation.

[001553] First, the effect of different VSV-G sequences on VLP formation was tested in polypeptides that comprise an RBD of a SARS-CoV-2 S protein. The constructs tested in the present Example are listed below and also indicated in Figs. 20(A) and (B).

. 4425: RBD-(G4S)4-TM(Cdell9)

. 4421: RBD-(G4S)3-VSV-G_short

. 4423: RBD-(G4S)3-VSV-G_mid_F440

• 4422: RBD-(G4S)3-VSV-G_mid_Q427

. 4424: RBD-(G4S)3-VSV-GJong

[001554] The membrane proximal sequences of the VSV-G_short, VSV-G_mid_F440, VSV-G_mid_Q427, and VSV-GJong are provided in Fig. 18(B) and also in Table 4. An RNA encoding an RBD and a SARS-CoV-2 transmembrane domain (4425) was also included as a control, as a SARS-CoV-2 S protein transmembrane domain is not known to induce VLP formation. Cell surface and supernatant expression of RBD is provided in Figs. 20(A) and (B). As shown in Fig. 20(A), an inverse correlation between cell surface expression and supernatant RBD signal was observed. In other words, RNA that produced higher cell surface RBD signal produced lower supernatant RBD signal. Each of the constructs comprising a VSV-G transmembrane domain resulted in reduced cell surface RBD signal and increased supernatant signal as compared to constructs comprising a transmembrane domain of a SARS-CoV-2 S protein, which is consistent with VSV-G domains described herein resulting in VLP formation. VSV-GJong and VSV-G_mid_Q427 may be especially effective in promoting VLP formation, as they produced the highest supernatant signal (~10x that produced by RNA encoding a polypeptide comprising a SARS-CoV-2 transmembrane domain; see Fig. 20(B)).

[001555] Next, the effect of different VSV-G sequences on VLP formation was tested when attached to a truncated SI domain. The constructs tested are indicated in Fig. 21 and are also listed below.

• 4462: NTD-RBD-(G4S)4-TM(Cdell9)

. 4458: NTD-RBD-(G4S)3-VSV-G_short . 4460: NTD-RBD-(G4S)3-VSV-G_mid_F440

. 4459: NTD-RBD-(G4S)3-VSV-G_mid_Q427

• 4461: NTD-RBD-(G4S)3-VSV-GJong

[001556] Cell surface and supernatant RBD signal is provided in Figs. 21(A) and (B). Once again, an inverse correlation between cell surface and supernatant RBD signal was observed, with each of the VSV-G domains tested resulting in increased supernatant signal and decreased cell surface signal as compared to an RNA encoding a polypeptide comprising a transmembrane domain of a SARS-CoV-2 S protein (4462), which is consistent with each of the VSV-G domains tested promoting increased VLP formation. VSV-G_mid_Q427 and VSV-GJong were again found to produce the highest supernatant signal (~4x that produced by RNA encoding a polypeptide comprising a SARS-CoV-2 transmembrane domain; see Fig. 20(B)), indicating that these VSV-G domains may be especially effective at promoting VLP formation.

[001557] Immunogecity was also tested in mice. One dose of constructs 2303 (encoding a full length S protein), 4459, 4461, 4425, and 4424 were administered to mice 21 days apart. 7, 14, 21, 28, and 35 days after the first dose, sera samples were collected and tested for XBB.1.5 neutralization titers using a pseudovirus assa. Results are shown in Figs. (A)-(F). As shown, all three VSV-G based NTD-RBD or RBD vaccine antigen showed nAb GMTs of between 46-80 7 days post immunization, which were comparable to those produced by 2303 (61). Neutralizing GMTs of 4459 NTD-RBD VSV-mid construct showed a considerable increase especially in between d21 and d28 (2.6-4.6-fold) compared to 2303. Similar titer increase behaviour was observed especially on d28 for all others three VSV-G based NTD-RBD or RBD vaccine antigen (>1.7-fold) compared to 2303 benchmark at all time points. Moreover, 2303 GMTs were already plateauing on d21, whereas nAb GMTs were still increasing for NTD-RBD vaccine designs. On d28/d35, titers for construct 4459 - harboring signal peptide SP25 and VSV-G-mid - were roughly 5.3-fold higher compared to the 2303 benchmark.

Optimizing GS Linker Length (VSV-G and (3-Annuius Peptide)

[001558] The effect of GS-linker length on both VLP formation and expression of constructs comprising a fJ- annulus peptide was also tested.

[001559] VSV-G: Constructs comprising a truncated SI domain and a VSV-G_mid_Q427 transmembrane domain were tested with different length linkers connecting the two. In the present Example, linker lengths of 5, 10, and 15 amino acids were tested ((G4S)1, (G4S)2, and (G4S)3). Cell surface expression results are provided in Fig. 23(A), and supernatant expression results are provided in Fig. 23(B). As shown in Fig. 23(A), a GS linker of 5 or 10 amino acids resulted in improved membrane expression as compared to a GS linker of 15 amino acids, with a linker of 5 amino acids providing for slightly improved expression as compared to a GS linker of 10 amino acids. As shown in Fig. 23(B), a GS linker of 5 or 10 amino acids also resulted in increased supernatant expression as compared to a GS linker of 15 amino acids. Thus, in some embodiments, including a GS linker of about 5 or 10 amino acids may result in improved antigen expression for constructs comprising a VSV-G transmembrane domain.

[001560] p-annulus peptide: The effect of linker length on antigen expression was also tested for an RNA encoding a polypeptide comprising a truncated SI polypeptide and a p-annulus peptide, where the SI polypeptide and [3-annulus peptide were connected via a GS linker comprising 5, 10, 15, or 20 amino acids. As shown in Fig. 23(C), a GS linker length of 5 amino acids provided increased antigen expression at lower concentrations of RNA. Thus, in some embodiments, including a GS linker of about 5 amino acids may result in improved antigen expression for constructs comprising a p-annulus peptide. Mouse Immunogenecity

[001561] Two doses of RNA encoding a polypeptide comprising a VSV-G transmembrane domain and RBD were also administered to mice and compared to RNA encoding a full length S protein to assess the immunogenicity in vivo. Serum samples were collected at regular intervals and neutralization titers were measured using a pseudovirus neutralization assay, using an XBB.1.5-adapted pseudovirus. Results are shown in Figs 19(A)-(F). As shown, a single dose of RBD-VSV vaccine antigen showed comparable nAb GMTs (of between 80-160), 7-21 days post immunization and were comparable with titers induced by the BNT162b2 benchmark. 7 days after a second dose, neutralizing GMTs of construct 3619 (comprising a VSV-G_short sequence) were 1.5- fold increased compared to BN162b2 benchmark. Titers for both constructs decreased 14 days post-boost, which was in particular pronounced for BNT162b2 benchmark while titer for 3619 trend remained stable.

[001562] Two doses of RNA encoding a polypeptide comprising a VSV-G transmembrane domain and a truncated SI subdomain (aino acids 1-528 in the present Example) were also administered to mice and compared to RNA encoding a full length S protein to assess the immunogenicity in vivo. Serum samples were collected at regular intervals and neutralization titers were measured using a pseudovirus neutralization assay, using an XBB.l.S-adapted pseudovirus. Results are shown in Figs 22(A)-(F). All three VSV-G based NTD-RBD or RBD vaccine antigens show nAb GMTs of between 46-80, 7 days post immunization and were comparable with titers of the BNT162b2 benchmark (61). Neutralizing GMTs of 4459 NTD-RBD VSV-mid construct show a considerable increase especially in-between d21 and d28 (2.6-4.6-fold) compared to BNT162b2. Similar titer increase behaviour was observed especially on d28 for all others three VSV-G based NTD-RBD or RBD vaccine antigen (>1.7-fold) compared to BNT162b2 benchmark at all time points. Moreover, BNT162b2 GMTs were already plateauing on d21, whereas nAb GMTs were still increasing for NTD-RBD vaccine designs. On d28/d35, titers for construct 4459 - harboring the signal peptide SP25 and VSV-G-mid - were roughly 5.3-fold higher compared to the BNT162b2 benchmark.

Sequence Listing Information:

DTD Version: Vl_3 File Name: 2013237-0687. xml Software Name: WIPO Sequence Software Version: 2.3.0 Production Date: 2023-06-26

General Information:

Current application / IP Office: US

Current application / Applicant file reference: 2013237-0687 Earliest priority application / IP Office: US Earliest priority application / Application number: 63/283,976 Earliest priority application / Filing date: 2021-11-29 Applicant name: BioNTech SE Applicant name / Language: en Inventor name: Alexander Muik Inventor name / Language: en Invention title: CORONAVIRUS VACCINE ( en ) Sequence Total Quantity: 177

Sequences :

Sequence Number (ID): 1

Length: 1273

Molecule Type: AA Features Location/Qualifiers :

- REGION, 1..1273

> note, S protein

- source, 1. .1273

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS 60

NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV 120

NNATNWIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE 180

GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NLVRDLPQGF SALEPLVDLP IGINITRFQT 240

LLALHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK 300

CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN 360

CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD 420

YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC 480

NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN 540

FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILDITPC SFGGVSVITP 600

GTNTSNQVAV LYQDVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEHVNNSY 660

ECDIPIGAGI CASYQTQTNS PRRARSVASQ SIIAYTMSLG AENSVAYSNN SIAIPTNFTI 720

SVTTEILPVS MTKTSVDCTM YICGDSTECS NLLLQYGSFC TQLNRALTGI AVEQDKNTQE 780

VFAQVKQIYK TPPIKDFGGF NFSQILPDPS KPSKRSFIED LLFNKVTLAD AGFIKQYGDC 840

LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFGA GAALQIPFAM 900

QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TASALGKLQD WNQNAQALN 960

TLVKQLSSNF GAISSVLNDI LSRLDKVEAE VQIDRLITGR LQSLQTYVTQ QLIRAAEIRA

1020

SANLAATKMS ECVLGQSKRV DFCGKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA

1080

ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDWI GIVNNTVYDP 1140

LQPELDSFKE ELDKYFKNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL

1200

QE LGKYEQYI KWPWYIWLGF IAGLIAIVMV TIMLCCMTSC CSCLKGCCSC GSCCKFDEDD

1260

SEPVLKGVKL HYT

1273

Sequence Number (ID) : 2

Length : 3819

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .3819

> note, Coding Sequence

- source, 1 . . 3819

> mol_type, other RNA

> organism, synthetic construct Residues : atgtttgtgt ttcttgtgct gctgcctctt gtgtcttctc agtgtgtgaa tttgacaaca 60 agaacacagc tgccaccagc ttatacaaat tcttttacca gaggagtgta ttatcctgat 120 aaagtgttta gatcttctgt gctgcacagc acacaggacc tgtttctgcc attttttagc 180 aatgtgacat ggtttcatgc aattcatgtg tctggaacaa atggaacaaa aagatttgat 240 aatcctgtgc tgccttttaa tgatggagtg tattttgctt caacagaaaa gtcaaatatt 300 attagaggat ggatttttgg aacaacactg gattctaaaa cacagtctct gctgattgtg 360 aataatgcaa caaatgtggt gattaaagtg tgtgaatttc agttttgtaa tgatcctttt 420 ctgggagtgt attatcacaa aaataataaa tcttggatgg aatctgaatt tagagtgtat 480 tcctctgcaa ataattgtac atttgaatat gtgtctcagc cttttctgat ggatctggaa 540 ggaaaacagg gcaattttaa aaatctgaga gaatttgtgt ttaaaaatat tgatggatat 600 tttaaaattt attctaaaca cacaccaatt aatttagtga gagatctgcc tcagggattt 660 tctgctctgg aacctctggt ggatctgcca attggcatta atattacaag atttcagaca 720 ctgctggctc tgcacagatc ttatctgaca cctggagatt cttcttctgg atggacagcc 780 ggagctgcag cttattatgt gggctatctg cagccaagaa catttctgct gaaatataat 840 gaaaatggaa caattacaga tgctgtggat tgtgctctgg atcctctgtc tgaaacaaaa 900 tgtacattaa aatcttttac agtggaaaaa ggcatttatc agacatctaa ttttagagtg 960 cagccaacag aatctattgt gagatttcca aatattacaa atctgtgtcc atttggagaa

1020 gtgtttaatg caacaagatt tgcatctgtg tatgcatgga atagaaaaag aatttctaat

1080 tgtgtggctg attattctgt gctgtataat agtgcttctt tttccacatt taaatgttat

1140 ggagtgtctc caacaaaatt aaatgattta tgttttacaa atgtgtatgc tgattctttt

1200 gtgatcagag gtgatgaagt gagacagatt gcccccggac agacaggaaa aattgctgat

1260 tacaattaca aactgcctga tgattttaca ggatgtgtga ttgcttggaa ttctaataat

1320 ttagattcta aagtgggagg aaattacaat tatctgtaca gactgtttag aaaatcaaat

1380 ctgaaacctt ttgaaagaga tatttcaaca gaaatttatc aggctggatc aacaccttgt

1440 aatggagtgg aaggatttaa ttgttatttt ccattacaga gctatggatt tcagccaacc

1500 aatggtgtgg gatatcagcc atatagagtg gtggtgctgt cttttgaact gctgcatgca

1560 cctgcaacag tgtgtggacc taaaaaatct acaaatttag tgaaaaataa atgtgtgaat

1620 tttaatttta atggattaac aggaacagga gtgctgacag aatctaataa aaaatttctg

1680 ccttttcagc agtttggcag agatattgca gataccacag atgcagtgag agatcctcag

1740 acattagaaa ttctggatat tacaccttgt tcttttgggg gtgtgtctgt gattacacct

1800 ggaacaaata catctaatca ggtggctgtg ctgtatcagg atgtgaattg tacagaagtg

1860 ccagtggcaa ttcatgcaga tcagctgaca ccaacatgga gagtgtattc tacaggatct

1920 aatgtgtttc agacaagagc aggatgtctg attggagcag aacatgtgaa taattcttat

1980 gaatgtgata ttccaattgg agcaggcatt tgtgcatctt atcagacaca gacaaattcc

2040 ccaaggagag caagatctgt ggcatctcag tctattattg catacaccat gtctctggga

2100 gcagaaaatt ctgtggcata ttctaataat tctattgcta ttccaacaaa ttttaccatt

2160 tctgtgacaa cagaaatttt acctgtgtct atgacaaaaa catctgtgga ttgtaccatg

2220 tacatttgtg gagattctac agaatgttct aatctgctgc tgcagtatgg atctttttgt

2280 acacagctga atagagcttt aacaggaatt gctgtggaac aggataaaaa tacacaggaa

2340 gtgtttgctc aggtgaaaca gatttacaaa acaccaccaa ttaaagattt tggaggattt

2400 aattttagcc agattctgcc tgatccttct aaaccttcta aaagatcttt tattgaagat

2460 ctgctgttta ataaagtgac actggcagat gcaggattta ttaaacagta tggagattgc

2520 ctgggtgata ttgctgcaag agatctgatt tgtgctcaga aatttaatgg actgacagtg

2580 ctgcctcctc tgctgacaga tgaaatgatt gctcagtaca catctgcttt actggctgga

2640 acaattacaa gcggatggac atttggagct ggagctgctc tgcagattcc ttttgcaatg

2700 cagatggctt acagatttaa tggaattgga gtgacacaga atgtgttata tgaaaatcag

2760 aaactgattg caaatcagtt taattctgca attggcaaaa ttcaggattc tctgtcttct

2820 acagcttctg ctctgggaaa actgcaggat gtggtgaatc agaatgcaca ggcactgaat

2880 actctggtga aacagctgtc tagcaatttt ggggcaattt cttctgtgct gaatgatatt

2940 ctgtctagac tggataaagt ggaagctgaa gtgcagattg atagactgat cacaggaaga

3000 ctgcagtctc tgcagactta tgtgacacag cagctgatta gagctgctga aattagagct

3060 tctgctaatc tggctgctac aaaaatgtct gaatgtgtgc tgggacagtc aaaaagagtg

3120 gatttttgtg gaaaaggata tcatctgatg tcttttccac agtctgctcc acatggagtg

3180 gtgtttttac atgtgacata tgtgccagca caggaaaaga attttaccac agcaccagca

3240 atttgtcatg atggaaaagc acattttcca agagaaggag tgtttgtgtc taatggaaca

3300 cattggtttg tgacacagag aaatttttat gaacctcaga ttattacaac agataataca

3360 tttgtgtcag gaaattgtga tgtggtgatt ggaattgtga ataatacagt gtatgatcca

3420 ctgcagccag aactggattc ttttaaagaa gaactggata aatattttaa aaatcacaca

3480 tctcctgatg tggatttagg agatatttct ggaatcaatg catctgtggt gaatattcag

3540 aaagaaattg atagactgaa tgaagtggcc aaaaatctga atgaatctct gattgatctg

3600 caggaacttg gaaaatatga acagtacatt aaatggcctt ggtacatttg gcttggattt

3660 attgcaggat taattgcaat tgtgatggtg acaattatgt tatgttgtat gacatcatgt

3720 tgttcttgtt taaaaggatg ttgttcttgt ggaagctgtt gtaaatttga tgaagatgat

3780 tctgaacctg tgttaaaagg agtgaaattg cattacaca

3819

Sequence Number (ID) : 3 Length : 218 Molecule Type : AA Features Location/Qualif iers :

- REGION j 1. .218

> note, S Protein RBD Fusion

- source, 1 . . 218

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCWRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN 60

SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT 120

GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVEGFNCYF 180

PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPK 218

Sequence Number (ID) : 4 Length : 654

Molecule Type : RNA

Features Location/Qualif iers : - misc_feature, 1. .654

> note, Coding Sequence

- source, 1. .654

> mol_type, other RNA

> organism, synthetic construct Residues : atgtttgtgt ttcttgtgct gctgcctctt gtgtcttctc agtgtgtggt gagatttcca 60 aatattacaa atctgtgtcc atttggagaa gtgtttaatg caacaagatt tgcatctgtg 120 tatgcatgga atagaaaaag aatttctaat tgtgtggctg attattctgt gctgtataat 180 agtgcttctt tttccacatt taaatgttat ggagtgtctc caacaaaatt aaatgattta 240 tgttttacaa atgtgtatgc tgattctttt gtgatcagag gtgatgaagt gagacagatt 300 gcccccggac agacaggaaa aattgctgat tacaattaca aactgcctga tgattttaca 360 ggatgtgtga ttgcttggaa ttctaataat ttagattcta aagtgggagg aaattacaat 420 tatctgtaca gactgtttag aaaatcaaat ctgaaacctt ttgaaagaga tatttcaaca 480 gaaatttatc aggctggatc aacaccttgt aatggagtgg aaggatttaa ttgttatttt 540 ccattacaga gctatggatt tcagccaacc aatggtgtgg gatatcagcc atatagagtg 600 gtggtgctgt cttttgaact gctgcatgca cctgcaacag tgtgtggacc taaa 654

Sequence Number (ID) : 5

Length : 266

Molecule Type : AA

Features Location/Qualif iers :

- REGION, 1. .266

> note, S Protein RBD Fusion

- source, 1 . . 266

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCWRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN 60

SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT 120

GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVEGFNCYF 180

PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKGS PGSGSGSGYI PEAPRDGQAY 240

VRKDGEWVLL STFLGRSLEV LFQGPG 266

Sequence Number (ID) : 6

Length : 798

Molecule Type : RNA

Features Location/Qualif iers :

- misc_feature, 1. .798

> note, Coding Sequence

- source, 1 . . 798

> mol_type, other RNA

> organism, synthetic construct Residues : atgtttgtgt ttcttgtgct gctgcctctt gtgtcttctc agtgtgtggt gagatttcca 60 aatattacaa atctgtgtcc atttggagaa gtgtttaatg caacaagatt tgcatctgtg 120 tatgcatgga atagaaaaag aatttctaat ■tgtgtggctg attattctgt gctgtataat 180 agtgcttctt tttccacatt taaatgttat ggagtgtctc caacaaaatt aaatgattta 240 tgttttacaa atgtgtatgc tgattctttt gtgatcagag gtgatgaagt gagacagatt 300 gcccccggac agacaggaaa aattgctgat tacaattaca aactgcctga tgattttaca 360 ggatgtgtga ttgcttggaa ttctaataat ttagattcta aagtgggagg aaattacaat 420 tatctgtaca gactgtttag aaaatcaaat ctgaaacctt ttgaaagaga tatttcaaca 480 gaaatttatc aggctggatc aacaccttgt aatggagtgg aaggatttaa ttgttatttt 540 ccattacaga gctatggatt tcagccaacc aatggtgtgg gatatcagcc atatagagtg 600 gtggtgctgt cttttgaact gctgcatgca cctgcaacag tgtgtggacc taaaggctcc 660 cc cggctccg gctccggatc tggttatatt cctgaagctc caagagatgg gcaagcttac 720 gttcgtaaag atggcgaatg ggtattactt tctacctttt taggccggtc cctggaggtg 780 ctgttc cagg gccccggc 798

Sequence Number ( ID) : 7 Length : 1273 Molecule Type : AA Features Location/Qualifiers :

- REGION j 1 . . 1273

> note, S Protein Variant

- source, 1 . . 1273

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLF LPF FS 60

NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV 120

NNATNVVIKV CE FQFCNDPF LGVYYHKNNK SWMESE FRVY SSANNCTFEY VSQPF LMDLE 180

GKQGNFKNLR E FVFKNIDGY FKIYSKHTPI NLVRDLPQGF SALEPLVDLP IGINITRFQT 240

LLALHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTF LLKYN ENGTITDAVD CALDPLSETK 300

CTLKS FTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN 360

CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADS F VIRGDEVRQI APGQTGKIAD 420

YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRL FRKSN LKPF ERDIST E IYQAGSTPC 480

NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV VVLSF E LLHA PATVCGPKKS TNLVKNKCVN 540

FNFNGLTGTG VLTESNKKF L PFQQFGRDIA DTTDAVRDPQ TLEI LDITPC S FGGVSVITP 600

GTNTSNQVAV LYQDVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEHVNNSY 660

ECDIPIGAGI CASYQTQTNS PRRARSVASQ SIIAYTMS LG AENSVAYSNN SIAI PTNFTI 720

SVTTEI LPVS MTKTSVDCTM YICGDSTECS NLLLQYGS FC TQLNRALTGI AVEQDKNTQE 780

VFAQVKQIYK TPPIKDFGGF NFSQI LPDPS KPSKRSFI ED LLFNKVTLAD AGFIKQYGDC 840

LGDIAARDLI CAQKFNGLTV LPPL LTDEMI AQYTSALLAG TITSGWTFGA GAALQIPFAM 900

QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TASALGKLQD VVNQNAQALN 960

TLVKQLSSNF GAISSVLNDI LSRLDPPEAE VQIDRLITGR LQSLQTYVTQ QLIRAAEI RA

1020 SANLAATKMS ECVLGQSKRV DFCGKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA

1080 ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDWI GIVNNTVYDP

1140 LQPELDSFKE E LDKYFKNHT SPDVDLGDIS GINASWNIQ KEIDRLNEVA KNLNESLIDL

1200 QE LGKYEQYI KWPWYIWLGF IAGLIAIVMV TIMLCCMTSC CSC LKGCCSC GSCCKFDEDD

1260 SEPVLKGVKL HYT

1273

Sequence Number ( ID) : 8 Length : 3819 Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .3819

> note, Coding Sequence

- source, 1. . 3819

> mol_type, other RNA

> organism, synthetic construct

Residues : atgtttgtgt ttcttgtgct gctgcctctt gtgtcttctc agtgtgtgaa tttgacaaca 60 agaacacagc tgccaccagc ttatacaaat tcttttacca gaggagtgta ttatcctgat 120 aaagtgttta gatcttctgt gctgcacagc acacaggacc tgtttctgcc attttttagc 180 aatgtgacat ggtttcatgc aattcatgtg tctggaacaa atggaacaaa aagatttgat 240 aatcctgtgc tgccttttaa tgatggagtg tattttgctt caacagaaaa gtcaaatatt 300 attagaggat ggatttttgg aacaacactg gattctaaaa cacagtctct gctgattgtg 360 aataatgcaa caaatgtggt gattaaagtg tgtgaatttc agttttgtaa tgatcctttt 420 ctgggagtgt attatcacaa aaataataaa tcttggatgg aatctgaatt tagagtgtat 480 tcctctgcaa ataattgtac atttgaatat gtgtctcagc cttttctgat ggatctggaa 540 ggaaaacagg gcaattttaa aaatctgaga gaatttgtgt ttaaaaatat tgatggatat 600 tttaaaattt attctaaaca cacaccaatt aatttagtga gagatctgcc tcagggattt 660 tctgctctgg aacctctggt ggatctgcca attggcatta atattacaag atttcagaca 720 ctgctggctc tgcacagatc ttatctgaca cctggagatt cttcttctgg atggacagcc 780 ggagctgcag cttattatgt gggctatctg cagccaagaa catttctgct gaaatataat 840 gaaaatggaa caattacaga tgctgtggat tgtgctctgg atcctctgtc tgaaacaaaa 900 tgtacattaa aatcttttac agtggaaaaa ggcatttatc agacatctaa ttttagagtg 960 cagccaacag aatctattgt gagatttcca aatattacaa atctgtgtcc atttggagaa

1020 gtgtttaatg caacaagatt tgcatctgtg tatgcatgga atagaaaaag aatttctaat

1080 tgtgtggctg attattctgt gctgtataat agtgcttctt tttccacatt taaatgttat

1140 ggagtgtctc caacaaaatt aaatgattta tgttttacaa atgtgtatgc tgattctttt

1200 gtgatcagag gtgatgaagt gagacagatt gcccccggac agacaggaaa aattgctgat

1260 tacaattaca aactgcctga tgattttaca ggatgtgtga ttgcttggaa ttctaataat

1320 ttagattcta aagtgggagg aaattacaat tatctgtaca gactgtttag aaaatcaaat

1380 ctgaaacctt ttgaaagaga tatttcaaca gaaatttatc aggctggatc aacaccttgt

1440 aatggagtgg aaggatttaa ttgttatttt ccattacaga gctatggatt tcagccaacc

1500 aatggtgtgg gatatcagcc atatagagtg gtggtgctgt cttttgaact gctgcatgca

1560 cctgcaacag tgtgtggacc taaaaaatct acaaatttag tgaaaaataa atgtgtgaat

1620 tttaatttta atggattaac aggaacagga gtgctgacag aatctaataa aaaatttctg

1680 ccttttcagc agtttggcag agatattgca gataccacag atgcagtgag agatcctcag

1740 acattagaaa ttctggatat tacaccttgt tcttttgggg gtgtgtctgt gattacacct

1800 ggaacaaata catctaatca ggtggctgtg ctgtatcagg atgtgaattg tacagaagtg

1860 ccagtggcaa ttcatgcaga tcagctgaca ccaacatgga gagtgtattc tacaggatct

1920 aatgtgtttc agacaagagc aggatgtctg attggagcag aacatgtgaa taattcttat

1980 gaatgtgata ttccaattgg agcaggcatt tgtgcatctt atcagacaca gacaaattcc

2040 ccaaggagag caagatctgt ggcatctcag tctattattg catacaccat gtctctggga

2100 gcagaaaatt ctgtggcata ttctaataat tctattgcta ttccaacaaa ttttaccatt

2160 tctgtgacaa cagaaatttt acctgtgtct atgacaaaaa catctgtgga ttgtaccatg

2220 tacatttgtg gagattctac agaatgttct aatctgctgc tgcagtatgg atctttttgt

2280 acacagctga atagagcttt aacaggaatt gctgtggaac aggataaaaa tacacaggaa

2340 gtgtttgctc aggtgaaaca gatttacaaa acaccaccaa ttaaagattt tggaggattt

2400 aattttagcc agattctgcc tgatccttct aaaccttcta aaagatcttt tattgaagat

2460 ctgctgttta ataaagtgac actggcagat gcaggattta ttaaacagta tggagattgc

2520 ctgggtgata ttgctgcaag agatctgatt tgtgctcaga aatttaatgg actgacagtg

2580 ctgcctcctc tgctgacaga tgaaatgatt gctcagtaca catctgcttt actggctgga

2640 acaattacaa gcggatggac atttggagct ggagctgctc tgcagattcc ttttgcaatg

2700 cagatggctt acagatttaa tggaattgga gtgacacaga atgtgttata tgaaaatcag

2760 aaactgattg caaatcagtt taattctgca attggcaaaa ttcaggattc tctgtcttct

2820 acagcttctg ctctgggaaa actgcaggat gtggtgaatc agaatgcaca ggcactgaat

2880 actctggtga aacagctgtc tagcaatttt ggggcaattt cttctgtgct gaatgatatt

2940 ctgtctagac tggatcctcc tgaagctgaa gtgcagattg atagactgat cacaggaaga

3000 ctgcagtctc tgcagactta tgtgacacag cagctgatta gagctgctga aattagagct

3060 tctgctaatc tggctgctac aaaaatgtct gaatgtgtgc tgggacagtc aaaaagagtg

3120 gatttttgtg gaaaaggata tcatctgatg tcttttccac agtctgctcc acatggagtg

3180 gtgtttttac atgtgacata tgtgccagca caggaaaaga attttaccac agcaccagca

3240 atttgtcatg atggaaaagc acattttcca agagaaggag tgtttgtgtc taatggaaca

3300 cattggtttg tgacacagag aaatttttat gaacctcaga ttattacaac agataataca

3360 tttgtgtcag gaaattgtga tgtggtgatt ggaattgtga ataatacagt gtatgatcca

3420 ctgcagccag aactggattc ttttaaagaa gaactggata aatattttaa aaatcacaca

3480 tctcctgatg tggatttagg agatatttct ggaatcaatg catctgtggt gaatattcag

3540 aaagaaattg atagactgaa tgaagtggcc aaaaatctga atgaatctct gattgatctg

3600 caggaacttg gaaaatatga acagtacatt aaatggcctt ggtacatttg gcttggattt

3660 attgcaggat taattgcaat tgtgatggtg acaattatgt tatgttgtat gacatcatgt

3720 tgttcttgtt taaaaggatg ttgttcttgt ggaagctgtt gtaaatttga tgaagatgat

3780 tctgaacctg tgttaaaagg agtgaaattg cattacaca

3819

Sequence Number ( ID) : 9

Length : 3819

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .3819

> note, Coding Sequence

- source, 1 . . 3819

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240 aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300 atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360 aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420 ctgggcgtct actaccacaa gaacaacaag agctggatgg aaagcgagtt ccgggtgtac 480 agcagcgcca acaactgcac cttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggcaagcagg gcaacttcaa gaacctgcgc gagttcgtgt ttaagaacat cgacggctac 600 ttcaagatct acagcaagca cacccctatc aacctcgtgc gggatctgcc tcagggcttc 660 tctgctctgg aacccctggt ggatctgccc atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cctggcgata gcagcagcgg atggacagct 780 ggtgccgccg cttactatgt gggctacctg cagcctagaa ccttcctgct gaagtacaac 840 gagaacggca ccatcaccga cgccgtggat tgtgctctgg atcctctgag cgagacaaag 900 tgcaccctga agtccttcac cgtggaaaag ggcatctacc agaccagcaa cttccgggtg 960 cagcccaccg aatccatcgt gcggttcccc aatatcacca atctgtgccc cttcggcgag

1020 gtgttcaatg ccaccagatt cgcctctgtg tacgcctgga accggaagcg gatcagcaat 1080 tgcgtggccg actactccgt gctgtacaac tccgccagct tcagcacctt caagtgctac

1140 ggcgtgtccc ctaccaagct gaacgacctg tgcttcacaa acgtgtacgc cgacagcttc

1200 gtgatccggg gagatgaagt gcggcagatt gcccctggac agacaggcaa gatcgccgac

1260 tacaactaca agctgcccga cgacttcacc ggctgtgtga ttgcctggaa cagcaacaac

1320 ctggactcca aagtcggcgg caactacaat tacctgtacc ggctgttccg gaagtccaat

1380 ctgaagccct tcgagcggga catctccacc gagatctatc aggccggcag caccccttgt

1440 aacggcgtgg aaggcttcaa ctgctacttc ccactgcagt cctacggctt tcagcccaca

1500 aatggcgtgg gctatcagcc ctacagagtg gtggtgctga gcttcgaact gctgcatgcc

1560 cctgccacag tgtgcggccc taagaaaagc accaatctcg tgaagaacaa atgcgtgaac

1620 ttcaacttca acggcctgac cggcaccggc gtgctgacag agagcaacaa gaagttcctg

1680 ccattccagc agtttggccg ggatatcgcc gataccacag acgccgttag agatccccag

1740 acactggaaa tcctggacat caccccttgc agcttcggcg gagtgtctgt gatcacccct

1800 ggcaccaaca ccagcaatca ggtggcagtg ctgtaccagg acgtgaactg taccgaagtg

1860 cccgtggcca ttcacgccga tcagctgaca cctacatggc gggtgtactc caccggcagc

1920 aatgtgtttc agaccagagc cggctgtctg atcggagccg agcacgtgaa caatagctac

1980 gagtgcgaca tccccatcgg cgctggaatc tgcgccagct accagacaca gacaaacagc

2040 cctcggagag ccagaagcgt ggccagccag agcatcattg cctacacaat gtctctgggc

2100 gccgagaaca gcgtggccta ctccaacaac tctatcgcta tccccaccaa cttcaccatc

2160 agcgtgacca cagagatcct gcctgtgtcc atgaccaaga ccagcgtgga ctgcaccatg

2220 tacatctgcg gcgattccac cgagtgctcc aacctgctgc tgcagtacgg cagcttctgc

2280 acccagctga atagagccct gacagggatc gccgtggaac aggacaagaa cacccaagag

2340 gtgttcgccc aagtgaagca gatctacaag acccctccta tcaaggactt cggcggcttc

2400 aatttcagcc agattctgcc cgatcctagc aagcccagca agcggagctt catcgaggac

2460 ctgctgttca acaaagtgac actggccgac gccggcttca tcaagcagta tggcgattgt

2520 ctgggcgaca ttgccgccag ggatctgatt tgcgcccaga agtttaacgg actgacagtg 2580 ctgcctcctc tgctgaccga tgagatgatc gcccagtaca catctgccct gctggccggc

2640 acaatcacaa gcggctggac atttggagca ggcgccgctc tgcagatccc ctttgctatg

2700 cagatggcct accggttcaa cggcatcgga gtgacccaga atgtgctgta cgagaaccag

2760 aagctgatcg ccaaccagtt caacagcgcc atcggcaaga tccaggacag cctgagcagc

2820 acagcaagcg ccctgggaaa gctgcaggac gtggtcaacc agaatgccca ggcactgaac

2880 accctggtca agcagctgtc ctccaacttc ggcgccatca gctctgtgct gaacgatatc

2940 ctgagcagac tggaccctcc tgaggccgag gtgcagatcg acagactgat cacaggcaga

3000 ctgcagagcc tccagacata cgtgacccag cagctgatca gagccgccga gattagagcc

3060 tctgccaatc tggccgccac caagatgtct gagtgtgtgc tgggccagag caagagagtg

3120 gacttttgcg gcaagggcta ccacctgatg agcttccctc agtctgcccc tcacggcgtg

3180 gtgtttctgc acgtgacata tgtgcccgct caagagaaga atttcaccac cgctccagcc

3240 atctgccacg acggcaaagc ccactttcct agagaaggcg tgttcgtgtc caacggcacc

3300 cattggttcg tgacacagcg gaacttctac gagccccaga tcatcaccac cgacaacacc

3360 ttcgtgtctg gcaactgcga cgtcgtgatc ggcattgtga acaataccgt gtacgaccct

3420 ctgcagcccg agctggacag cttcaaagag gaactggaca agtactttaa gaaccacaca

3480 agccccgacg tggacctggg cgatatcagc ggaatcaatg ccagcgtcgt gaacatccag

3540 aaagagatcg accggctgaa cgaggtggcc aagaatctga acgagagcct gatcgacctg

3600 caagaactgg ggaagtacga gcagtacatc aagtggccct ggtacatctg gctgggcttt

3660 atcgccggac tgattgccat cgtgatggtc acaatcatgc tgtgttgcat gaccagctgc

3720 tgtagctgcc tgaagggctg ttgtagctgt ggcagctgct gcaagttcga cgaggacgat

3780 tctgagcccg tgctgaaggg cgtgaaactg cactacaca

3819

Sequence Number (ID) : 10

Length : 41

Molecule Type : AA

Features Location/Qualif iers :

- REGION, 1. .41

> note, Foldon Sequence - source, 1. .41

> mol_type, protein

> organism, synthetic construct Residues :

GSGYIPEAPR DGQAYVRKDG EWVLLSTFLG RSLEVLFQGP G 41

Sequence Number (ID) : 11

Length : 123

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .123

> note, Coding Sequence

- source, 1 . . 123

> mol_type, other RNA

> organism, synthetic construct

Residues : ggatctggtt atattcctga agctccaaga gatgggcaag cttacgttcg taaagatggc 60 gaatgggtat tactttctac ctttttaggc cggtccctgg aggtgctgtt ccagggcccc 120 ggc 123

Sequence Number (ID) : 12

Length : 47

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .47

> note, 5 ' -UTR

- source, 1. .47

> mol_type, other RNA

> organism, synthetic construct

Residues : aactagtatt cttctggtcc ccacagactc agagagaacc cgccacc 47

Sequence Number (ID) : 13

Length : 278

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .278

> note, 3 ' -UTR

- source, 1. .278

> mol_type, other RNA

> organism, synthetic construct Residues : ctggtactgc atgcacgcaa tgctagctgc ccctttcccg tcctgggtac cccgagtctc 60 ccccgacctc gggtcccagg tatgctccca cctccacctg ccccactcac cacctctgct 120 agttccagac acctcccaag cacgcagcaa tgcagctcaa aacgcttagc ctagccacac 180 ccccacggga aacagcagtg attaaccttt agcaataaac gaaagtttaa ctaagctata 240 ctaaccccag ggttggtcaa tttcgtgcca gccacacc 278

Sequence Number (ID) : 14 Length : 110 Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .110

> note, A30L70

- source, 1. .110

> mol_type, other RNA

> organism, synthetic construct Residues : aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa gcatatgact aaaaaaaaaa aaaaaaaaaa 60 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 110

Sequence Number (ID) : 15 Length : 4282

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .4282

> note, RBL063.1 source, 1. .4282

> mol_type, other RNA

> organism, synthetic construct

Residues : gggcgaacta gtattcttct ggtccccaca gactcagaga gaacccgcca ccatgtttgt 60 gtttcttgtg ctgctgcctc ttgtgtcttc tcagtgtgtg aatttgacaa caagaacaca 120 gctgccacca gcttatacaa attcttttac cagaggagtg tattatcctg ataaagtgtt 180 tagatcttct gtgctgcaca gcacacagga cctgtttctg ccatttttta gcaatgtgac 240 atggtttcat gcaattcatg tgtctggaac aaatggaaca aaaagatttg ataatcctgt 300 gctgcctttt aatgatggag tgtattttgc ttcaacagaa aagtcaaata ttattagagg 360 atggattttt ggaacaacac tggattctaa aacacagtct ctgctgattg tgaataatgc 420 aacaaatgtg gtgattaaag tgtgtgaatt tcagttttgt aatgatcctt ttctgggagt 480 gtattatcac aaaaataata aatcttggat ggaatctgaa tttagagtgt attcctctgc 540 aaataattgt acatttgaat atgtgtctca gccttttctg atggatctgg aaggaaaaca 600 gggcaatttt aaaaatctga gagaatttgt gtttaaaaat attgatggat attttaaaat 660 ttattctaaa cacacaccaa ttaatttagt gagagatctg cctcagggat tttctgctct 720 ggaacctctg gtggatctgc caattggcat taatattaca agatttcaga cactgctggc 780 tctgcacaga tcttatctga cacctggaga ttcttcttct ggatggacag ccggagctgc 840 agcttattat gtgggctatc tgcagccaag aacatttctg ctgaaatata atgaaaatgg 900 aacaattaca gatgctgtgg attgtgctct ggatcctctg tctgaaacaa aatgtacatt 960 aaaatctttt acagtggaaa aaggcattta tcagacatct aattttagag tgcagccaac

1020 agaatctatt gtgagatttc caaatattac aaatctgtgt ccatttggag aagtgtttaa

1080 tgcaacaaga tttgcatctg tgtatgcatg gaatagaaaa agaatttcta attgtgtggc

1140 tgattattct gtgctgtata atagtgcttc tttttccaca tttaaatgtt atggagtgtc

1200 tccaacaaaa ttaaatgatt tatgttttac aaatgtgtat gctgattctt ttgtgatcag

1260 aggtgatgaa gtgagacaga ttgcccccgg acagacagga aaaattgctg attacaatta

1320 caaactgcct gatgatttta caggatgtgt gattgcttgg aattctaata atttagattc 1380 taaagtggga ggaaattaca attatctgta cagactgttt agaaaatcaa atctgaaacc

1440 ttttgaaaga gatatttcaa cagaaattta tcaggctgga tcaacacctt gtaatggagt

1500 ggaaggattt aattgttatt ttccattaca gagctatgga tttcagccaa ccaatggtgt

1560 gggatatcag ccatatagag tggtggtgct gtcttttgaa ctgctgcatg cacctgcaac

1620 agtgtgtgga cctaaaaaat ctacaaattt agtgaaaaat aaatgtgtga attttaattt

1680 taatggatta acaggaacag gagtgctgac agaatctaat aaaaaatttc tgccttttca

1740 gcagtttggc agagatattg cagataccac agatgcagtg agagatcctc agacattaga

1800 aattctggat attacacctt gttcttttgg gggtgtgtct gtgattacac ctggaacaaa

1860 tacatctaat caggtggctg tgctgtatca ggatgtgaat tgtacagaag tgccagtggc

1920 aattcatgca gatcagctga caccaacatg gagagtgtat tctacaggat ctaatgtgtt

1980 tcagacaaga gcaggatgtc tgattggagc agaacatgtg aataattctt atgaatgtga

2040 tattccaatt ggagcaggca tttgtgcatc ttatcagaca cagacaaatt ccccaaggag

2100 agcaagatct gtggcatctc agtctattat tgcatacacc atgtctctgg gagcagaaaa

2160 ttctgtggca tattctaata attctattgc tattccaaca aattttacca tttctgtgac

2220 aacagaaatt ttacctgtgt ctatgacaaa aacatctgtg gattgtacca tgtacatttg

2280 tggagattct acagaatgtt ctaatctgct gctgcagtat ggatcttttt gtacacagct

2340 gaatagagct ttaacaggaa ttgctgtgga acaggataaa aatacacagg aagtgtttgc

2400 tcaggtgaaa cagatttaca aaacaccacc aattaaagat tttggaggat ttaattttag

2460 ccagattctg cctgatcctt ctaaaccttc taaaagatct tttattgaag atctgctgtt

2520 taataaagtg acactggcag atgcaggatt tattaaacag tatggagatt gcctgggtga

2580 tattgctgca agagatctga tttgtgctca gaaatttaat ggactgacag tgctgcctcc

2640 tctgctgaca gatgaaatga ttgctcagta cacatctgct ttactggctg gaacaattac

2700 aagcggatgg acatttggag ctggagctgc tctgcagatt ccttttgcaa tgcagatggc

2760 ttacagattt aatggaattg gagtgacaca gaatgtgtta tatgaaaatc agaaactgat

2820 tgcaaatcag tttaattctg caattggcaa aattcaggat tctctgtctt ctacagcttc 2880 tgctctggga aaactgcagg atgtggtgaa tcagaatgca caggcactga atactctggt

2940 gaaacagctg tctagcaatt ttggggcaat ttcttctgtg ctgaatgata ttctgtctag

3000 actggatcct cctgaagctg aagtgcagat tgatagactg atcacaggaa gactgcagtc

3060 tctgcagact tatgtgacac agcagctgat tagagctgct gaaattagag cttctgctaa

3120 tctggctgct acaaaaatgt ctgaatgtgt gctgggacag tcaaaaagag tggatttttg

3180 tggaaaagga tatcatctga tgtcttttcc acagtctgct ccacatggag tggtgttttt

3240 acatgtgaca tatgtgccag cacaggaaaa gaattttacc acagcaccag caatttgtca

3300 tgatggaaaa gcacattttc caagagaagg agtgtttgtg tctaatggaa cacattggtt

3360 tgtgacacag agaaattttt atgaacctca gattattaca acagataata catttgtgtc

3420 aggaaattgt gatgtggtga ttggaattgt gaataataca gtgtatgatc cactgcagcc

3480 agaactggat tcttttaaag aagaactgga taaatatttt aaaaatcaca catctcctga

3540 tgtggattta ggagatattt ctggaatcaa tgcatctgtg gtgaatattc agaaagaaat

3600 tgatagactg aatgaagtgg ccaaaaatct gaatgaatct ctgattgatc tgcaggaact

3660 tggaaaatat gaacagtaca ttaaatggcc ttggtacatt tggcttggat ttattgcagg

3720 attaattgca attgtgatgg tgacaattat gttatgttgt atgacatcat gttgttcttg

3780 tttaaaagga tgttgttctt gtggaagctg ttgtaaattt gatgaagatg attctgaacc

3840 tgtgttaaaa ggagtgaaat tgcattacac atgatgactc gagctggtac tgcatgcacg

3900 caatgctagc tgcccctttc ccgtcctggg taccccgagt ctcccccgac ctcgggtccc

3960 aggtatgctc ccacctccac ctgccccact caccacctct gctagttcca gacacctccc

4020 aagcacgcag caatgcagct caaaacgctt agcctagcca cacccccacg ggaaacagca

4080 gtgattaacc tttagcaata aacgaaagtt taactaagct atactaaccc cagggttggt

4140 caatttcgtg ccagccacac cctggagcta gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4200 aagcatatga ctaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaaaaaaaa aa

4282 Sequence Number (ID) : 16

Length : 4282

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .4282

> note, RBL063.2

- source, 1. .4282

> mol_type, other RNA

> organism, synthetic construct Residues : gggcgaacta gtattcttct ggtccccaca gactcagaga gaacccgcca ccatgttcgt 60 gttcctggtg ctgctgcctc tggtgtccag ccagtgtgtg aacctgacca ccagaacaca 120 gctgcctcca gcctacacca acagctttac cagaggcgtg tactaccccg acaaggtgtt 180 cagatccagc gtgctgcact ctacccagga cctgttcctg cctttcttca gcaacgtgac 240 ctggttccac gccatccacg tgtccggcac caatggcacc aagagattcg acaaccccgt 300 gctgcccttc aacgacgggg tgtactttgc cagcaccgag aagtccaaca tcatcagagg 360 ctggatcttc ggcaccacac tggacagcaa gacccagagc ctgctgatcg tgaacaacgc 420 caccaacgtg gtcatcaaag tgtgcgagtt ccagttctgc aacgacccct tcctgggcgt 480 ctactaccac aagaacaaca agagctggat ggaaagcgag ttccgggtgt acagcagcgc 540 caacaactgc accttcgagt acgtgtccca gcctttcctg atggacctgg aaggcaagca 600 gggcaacttc aagaacctgc gcgagttcgt gtttaagaac atcgacggct acttcaagat 660 ctacagcaag cacaccccta tcaacctcgt gcgggatctg cctcagggct tctctgctct 720 ggaacccctg gtggatctgc ccatcggcat caacatcacc cggtttcaga cactgctggc 780 cctgcacaga agctacctga cacctggcga tagcagcagc ggatggacag ctggtgccgc 840 cgcttactat gtgggctacc tgcagcctag aaccttcctg ctgaagtaca acgagaacgg 900 caccatcacc gacgccgtgg attgtgctct ggatcctctg agcgagacaa agtgcaccct 960 gaagtccttc accgtggaaa agggcatcta ccagaccagc aacttccggg tgcagcccac

1020 cgaatccatc gtgcggttcc ccaatatcac caatctgtgc cccttcggcg aggtgttcaa

1080 tgccaccaga ttcgcctctg tgtacgcctg gaaccggaag cggatcagca attgcgtggc

1140 cgactactcc gtgctgtaca actccgccag cttcagcacc ttcaagtgct acggcgtgtc

1200 ccctaccaag ctgaacgacc tgtgcttcac aaacgtgtac gccgacagct tcgtgatccg

1260 gggagatgaa gtgcggcaga ttgcccctgg acagacaggc aagatcgccg actacaacta

1320 caagctgccc gacgacttca ccggctgtgt gattgcctgg aacagcaaca acctggactc

1380 caaagtcggc ggcaactaca attacctgta ccggctgttc cggaagtcca atctgaagcc

1440 cttcgagcgg gacatctcca ccgagatcta tcaggccggc agcacccctt gtaacggcgt

1500 ggaaggcttc aactgctact tcccactgca gtcctacggc tttcagccca caaatggcgt

1560 gggctatcag ccctacagag tggtggtgct gagcttcgaa ctgctgcatg cccctgccac

1620 agtgtgcggc cctaagaaaa gcaccaatct cgtgaagaac aaatgcgtga acttcaactt

1680 caacggcctg accggcaccg gcgtgctgac agagagcaac aagaagttcc tgccattcca

1740 gcagtttggc cgggatatcg ccgataccac agacgccgtt agagatcccc agacactgga

1800 aatcctggac atcacccctt gcagcttcgg cggagtgtct gtgatcaccc ctggcaccaa

1860 caccagcaat caggtggcag tgctgtacca ggacgtgaac tgtaccgaag tgcccgtggc

1920 cattcacgcc gatcagctga cacctacatg gcgggtgtac tccaccggca gcaatgtgtt

1980 tcagaccaga gccggctgtc tgatcggagc cgagcacgtg aacaatagct acgagtgcga

2040 catccccatc ggcgctggaa tctgcgccag ctaccagaca cagacaaaca gccctcggag

2100 agccagaagc gtggccagcc agagcatcat tgcctacaca atgtctctgg gcgccgagaa

2160 cagcgtggcc tactccaaca actctatcgc tatccccacc aacttcacca tcagcgtgac

2220 cacagagatc ctgcctgtgt ccatgaccaa gaccagcgtg gactgcacca tgtacatctg

2280 cggcgattcc accgagtgct ccaacctgct gctgcagtac ggcagcttct gcacccagct

2340 gaatagagcc ctgacaggga tcgccgtgga acaggacaag aacacccaag aggtgttcgc

2400 ccaagtgaag cagatctaca agacccctcc tatcaaggac ttcggcggct tcaatttcag

2460 ccagattctg cccgatccta gcaagcccag caagcggagc ttcatcgagg acctgctgtt

2520 caacaaagtg acactggccg acgccggctt catcaagcag tatggcgatt gtctgggcga

2580 cattgccgcc agggatctga tttgcgccca gaagtttaac ggactgacag tgctgcctcc

2640 tctgctgacc gatgagatga tcgcccagta cacatctgcc ctgctggccg gcacaatcac

2700 aagcggctgg acatttggag caggcgccgc tctgcagatc ccctttgcta tgcagatggc

2760 ctaccggttc aacggcatcg gagtgaccca gaatgtgctg tacgagaacc agaagctgat

2820 cgccaaccag ttcaacagcg ccatcggcaa gatccaggac agcctgagca gcacagcaag

2880 cgccctggga aagctgcagg acgtggtcaa ccagaatgcc caggcactga acaccctggt

2940 caagcagctg tcctccaact tcggcgccat cagctctgtg ctgaacgata tcctgagcag

3000 actggaccct cctgaggccg aggtgcagat cgacagactg atcacaggca gactgcagag

3060 cctccagaca tacgtgaccc agcagctgat cagagccgcc gagattagag cctctgccaa

3120 tctggccgcc accaagatgt ctgagtgtgt gctgggccag agcaagagag tggacttttg

3180 cggcaagggc taccacctga tgagcttccc tcagtctgcc cctcacggcg tggtgtttct

3240 gcacgtgaca tatgtgcccg ctcaagagaa gaatttcacc accgctccag ccatctgcca

3300 cgacggcaaa gcccactttc ctagagaagg cgtgttcgtg tccaacggca cccattggtt

3360 cgtgacacag cggaacttct acgagcccca gatcatcacc accgacaaca ccttcgtgtc

3420 tggcaactgc gacgtcgtga tcggcattgt gaacaatacc gtgtacgacc ctctgcagcc

3480 cgagctggac agcttcaaag aggaactgga caagtacttt aagaaccaca caagccccga

3540 cgtggacctg ggcgatatca gcggaatcaa tgccagcgtc gtgaacatcc agaaagagat

3600 cgaccggctg aacgaggtgg ccaagaatct gaacgagagc ctgatcgacc tgcaagaact

3660 ggggaagtac gagcagtaca tcaagtggcc ctggtacatc tggctgggct ttatcgccgg

3720 actgattgcc atcgtgatgg tcacaatcat gctgtgttgc atgaccagct gctgtagctg

3780 cctgaagggc tgttgtagct gtggcagctg ctgcaagttc gacgaggacg attctgagcc

3840 cgtgctgaag ggcgtgaaac tgcactacac atgatgactc gagctggtac tgcatgcacg

3900 caatgctagc tgcccctttc ccgtcctggg taccccgagt ctcccccgac ctcgggtccc

3960 aggtatgctc ccacctccac ctgccccact caccacctct gctagttcca gacacctccc

4020 aagcacgcag caatgcagct caaaacgctt agcctagcca cacccccacg ggaaacagca

4080 gtgattaacc tttagcaata aacgaaagtt taactaagct atactaaccc cagggttggt

4140 caatttcgtg ccagccacac cctggagcta gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4200 aagcatatga ctaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaaaaaaaa aa

4282

Sequence Number (ID) : 17

Length : 1261

Molecule Type : RNA

Features Location/Qualif iers :

- misc_feature, 1. .1261

> note, RBL063.3

- source, 1. .1261

> mol_type, other RNA

> organism, synthetic construct Residues : gggcgaacta gtattcttct ggtccccaca gactcagaga gaacccgcca ccatgtttgt 60 gtttcttgtg ctgctgcctc ttgtgtcttc tcagtgtgtg gtgagatttc caaatattac 120 aaatctgtgt ccatttggag aagtgtttaa tgcaacaaga tttgcatctg tgtatgcatg 180 gaatagaaaa agaatttcta attgtgtggc tgattattct gtgctgtata atagtgcttc 240 tttttccaca tttaaatgtt atggagtgtc tccaacaaaa ttaaatgatt tatgttttac 300 aaatgtgtat gctgattctt ttgtgatcag aggtgatgaa gtgagacaga ttgcccccgg 360 acagacagga aaaattgctg attacaatta caaactgcct gatgatttta caggatgtgt 420 gattgcttgg aattctaata atttagattc taaagtggga ggaaattaca attatctgta 480 cagactgttt agaaaatcaa atctgaaacc ttttgaaaga gatatttcaa cagaaattta 540 tcaggctgga tcaacacctt gtaatggagt ggaaggattt aattgttatt ttccattaca 600 gagctatgga tttcagccaa ccaatggtgt gggatatcag ccatatagag tggtggtgct 660 gtcttttgaa ctgctgcatg cacctgcaac agtgtgtgga cctaaaggct cccccggctc 720 cggctccgga tctggttata ttcctgaagc tccaagagat gggcaagctt acgttcgtaa 780 agatggcgaa tgggtattac tttctacctt tttaggccgg tccctggagg tgctgttcca 840 gggccccggc tgatgactcg agctggtact gcatgcacgc aatgctagct gcccctttcc 900 cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc cacctccacc 960 tgccccactc accacctctg ctagttccag acacctccca agcacgcagc aatgcagctc

1020 aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct ttagcaataa

1080 acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc cagccacacc

1140 ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac taaaaaaaaa

1200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

1260 a

1261

Sequence Number (ID) : 18

Length : 250

Molecule Type : AA

Features Location/Qualif iers :

- REGION j 1. .250

> note, S Protein RBD Fusion

- source, 1 . . 250

> mol_type, protein

> organism, synthetic construct Residues :

VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK 60

LNDLCFTNVY ADSFVIRGDE VRQIAPGQTG KIADYNYKLP DDFTGCVIAW NSNNLDSKVG 120

GNYNYLYRLF RKSNLKPFER DISTEIYQAG STPCNGVEGF NCYFPLQSYG FQPTNGVGYQ 180

PYRVWLSFE LLHAPATVCG PKGSPGSGSG SGYIPEAPRD GQAYVRKDGE WVLLSTFLGR 240

SLEVLFQGPG 250

Sequence Number (ID) : 19

Length : 4283

Molecule Type : RNA

Features Location/Qualif iers :

- misc_feature, 1. .4283

> note, RBP020.1 - source, 1. .4283

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgtttg 60 tgtttcttgt gctgctgcct cttgtgtctt ctcagtgtgt gaatttgaca acaagaacac 120 agctgccacc agcttataca aattctttta ccagaggagt gtattatcct gataaagtgt 180 ttagatcttc tgtgctgcac agcacacagg acctgtttct gccatttttt agcaatgtga 240 catggtttca tgcaattcat gtgtctggaa caaatggaac aaaaagattt gataatcctg 300 tgctgccttt taatgatgga gtgtattttg cttcaacaga aaagtcaaat attattagag 360 gatggatttt tggaacaaca ctggattcta aaacacagtc tctgctgatt gtgaataatg 420 caacaaatgt ggtgattaaa gtgtgtgaat ttcagttttg taatgatcct tttctgggag 480 tgtattatca caaaaataat aaatcttgga tggaatctga atttagagtg tattcctctg 540 caaataattg tacatttgaa tatgtgtctc agccttttct gatggatctg gaaggaaaac 600 agggcaattt taaaaatctg agagaatttg tgtttaaaaa tattgatgga tattttaaaa 660 tttattctaa acacacacca attaatttag tgagagatct gcctcaggga ttttctgctc 720 tggaacctct ggtggatctg ccaattggca ttaatattac aagatttcag acactgctgg 780 ctctgcacag atcttatctg acacctggag attcttcttc tggatggaca gccggagctg 840 cagcttatta tgtgggctat ctgcagccaa gaacatttct gctgaaatat aatgaaaatg 900 gaacaattac agatgctgtg gattgtgctc tggatcctct gtctgaaaca aaatgtacat 960 taaaatcttt tacagtggaa aaaggcattt atcagacatc taattttaga gtgcagccaa

1020 cagaatctat tgtgagattt ccaaatatta caaatctgtg tccatttgga gaagtgttta

1080 atgcaacaag atttgcatct gtgtatgcat ggaatagaaa aagaatttct aattgtgtgg

1140 ctgattattc tgtgctgtat aatagtgctt ctttttccac atttaaatgt tatggagtgt

1200 ctccaacaaa attaaatgat ttatgtttta caaatgtgta tgctgattct tttgtgatca

1260 gaggtgatga agtgagacag attgcccccg gacagacagg aaaaattgct gattacaatt

1320 acaaactgcc tgatgatttt acaggatgtg tgattgcttg gaattctaat aatttagatt

1380 ctaaagtggg aggaaattac aattatctgt acagactgtt tagaaaatca aatctgaaac

1440 cttttgaaag agatatttca acagaaattt atcaggctgg atcaacacct tgtaatggag

1500 tggaaggatt taattgttat tttccattac agagctatgg atttcagcca accaatggtg

1560 tgggatatca gccatataga gtggtggtgc tgtcttttga actgctgcat gcacctgcaa

1620 cagtgtgtgg acctaaaaaa tctacaaatt tagtgaaaaa taaatgtgtg aattttaatt

1680 ttaatggatt aacaggaaca ggagtgctga cagaatctaa taaaaaattt ctgccttttc

1740 agcagtttgg cagagatatt gcagatacca cagatgcagt gagagatcct cagacattag

1800 aaattctgga tattacacct tgttcttttg ggggtgtgtc tgtgattaca cctggaacaa

1860 atacatctaa tcaggtggct gtgctgtatc aggatgtgaa ttgtacagaa gtgccagtgg

1920 caattcatgc agatcagctg acaccaacat ggagagtgta ttctacagga tctaatgtgt

1980 ttcagacaag agcaggatgt ctgattggag cagaacatgt gaataattct tatgaatgtg

2040 atattccaat tggagcaggc atttgtgcat cttatcagac acagacaaat tccccaagga

2100 gagcaagatc tgtggcatct cagtctatta ttgcatacac catgtctctg ggagcagaaa

2160 attctgtggc atattctaat aattctattg ctattccaac aaattttacc atttctgtga

2220 caacagaaat tttacctgtg tctatgacaa aaacatctgt ggattgtacc atgtacattt

2280 gtggagattc tacagaatgt tctaatctgc tgctgcagta tggatctttt tgtacacagc

2340 tgaatagagc tttaacagga attgctgtgg aacaggataa aaatacacag gaagtgtttg

2400 ctcaggtgaa acagatttac aaaacaccac caattaaaga ttttggagga tttaatttta

2460 gccagattct gcctgatcct tctaaacctt ctaaaagatc ttttattgaa gatctgctgt

2520 ttaataaagt gacactggca gatgcaggat ttattaaaca gtatggagat tgcctgggtg

2580 atattgctgc aagagatctg atttgtgctc agaaatttaa tggactgaca gtgctgcctc

2640 ctctgctgac agatgaaatg attgctcagt acacatctgc tttactggct ggaacaatta

2700 caagcggatg gacatttgga gctggagctg ctctgcagat tccttttgca atgcagatgg

2760 cttacagatt taatggaatt ggagtgacac agaatgtgtt atatgaaaat cagaaactga

2820 ttgcaaatca gtttaattct gcaattggca aaattcagga ttctctgtct tctacagctt

2880 ctgctctggg aaaactgcag gatgtggtga atcagaatgc acaggcactg aatactctgg

2940 tgaaacagct gtctagcaat tttggggcaa tttcttctgt gctgaatgat attctgtcta

3000 gactggatcc tcctgaagct gaagtgcaga ttgatagact gatcacagga agactgcagt

3060 ctctgcagac ttatgtgaca cagcagctga ttagagctgc tgaaattaga gcttctgcta

3120 atctggctgc tacaaaaatg tctgaatgtg tgctgggaca gtcaaaaaga gtggattttt

3180 gtggaaaagg atatcatctg atgtcttttc cacagtctgc tccacatgga gtggtgtttt

3240 tacatgtgac atatgtgcca gcacaggaaa agaattttac cacagcacca gcaatttgtc

3300 atgatggaaa agcacatttt ccaagagaag gagtgtttgt gtctaatgga acacattggt

3360 ttgtgacaca gagaaatttt tatgaacctc agattattac aacagataat acatttgtgt

3420 caggaaattg tgatgtggtg attggaattg tgaataatac agtgtatgat ccactgcagc

3480 cagaactgga ttcttttaaa gaagaactgg ataaatattt taaaaatcac acatctcctg

3540 atgtggattt aggagatatt tctggaatca atgcatctgt ggtgaatatt cagaaagaaa

3600 ttgatagact gaatgaagtg gccaaaaatc tgaatgaatc tctgattgat ctgcaggaac

3660 ttggaaaata tgaacagtac attaaatggc cttggtacat ttggcttgga tttattgcag

3720 gattaattgc aattgtgatg gtgacaatta tgttatgttg tatgacatca tgttgttctt

3780 gtttaaaagg atgttgttct tgtggaagct gttgtaaatt tgatgaagat gattctgaac

3840 ctgtgttaaa aggagtgaaa ttgcattaca catgatgact cgagctggta ctgcatgcac

3900 gcaatgctag ctgccccttt cccgtcctgg gtaccccgag tctcccccga cctcgggtcc

3960 caggtatgct cccacctcca cctgccccac tcaccacctc tgctagttcc agacacctcc

4020 caagcacgca gcaatgcagc tcaaaacgct tagcctagcc acacccccac gggaaacagc

4080 agtgattaac ctttagcaat aaacgaaagt ttaactaagc tatactaacc ccagggttgg

4140 tcaatttcgt gccagccaca ccctggagct agcaaaaaaa aaaaaaaaaa aaaaaaaaaa

4200 aaagcatatg actaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaaaaaaaa aaa

4283

Sequence Number (ID) : 20

Length : 4283

Molecule Type : RNA

Features Location/Qualif iers :

- misc_feature, 1. .4283

> note, RBP020.2

- source, 1 . .4283

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgacc accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgccatccac gtgtccggca ccaatggcac caagagattc gacaaccccg 300 tgctgccctt caacgacggg gtgtactttg ccagcaccga gaagtccaac atcatcagag 360 gctggatctt cggcaccaca ctggacagca agacccagag cctgctgatc gtgaacaacg 420 ccaccaacgt ggtcatcaaa gtgtgcgagt tccagttctg caacgacccc ttcctgggcg 480 tctactacca caagaacaac aagagctgga tggaaagcga gttccgggtg tacagcagcg 540 ccaacaactg caccttcgag tacgtgtccc agcctttcct gatggacctg gaaggcaagc 600 agggcaactt caagaacctg cgcgagttcg tgtttaagaa catcgacggc tacttcaaga 660 tctacagcaa gcacacccct atcaacctcg tgcgggatct gcctcagggc ttctctgctc 720 tggaacccct ggtggatctg cccatcggca tcaacatcac ccggtttcag acactgctgg 780 ccctgcacag aagctacctg acacctggcg atagcagcag cggatggaca gctggtgccg 840 ccgcttacta tgtgggctac ctgcagccta gaaccttcct gctgaagtac aacgagaacg 900 gcaccatcac cgacgccgtg gattgtgctc tggatcctct gagcgagaca aagtgcaccc 960 tgaagtcctt caccgtggaa aagggcatct accagaccag caacttccgg gtgcagccca

1020 ccgaatccat cgtgcggttc cccaatatca ccaatctgtg ccccttcggc gaggtgttca

1080 atgccaccag attcgcctct gtgtacgcct ggaaccggaa gcggatcagc aattgcgtgg

1140 ccgactactc cgtgctgtac aactccgcca gcttcagcac cttcaagtgc tacggcgtgt

1200 cccctaccaa gctgaacgac ctgtgcttca caaacgtgta cgccgacagc ttcgtgatcc

1260 ggggagatga agtgcggcag attgcccctg gacagacagg caagatcgcc gactacaact

1320 acaagctgcc cgacgacttc accggctgtg tgattgcctg gaacagcaac aacctggact

1380 ccaaagtcgg cggcaactac aattacctgt accggctgtt ccggaagtcc aatctgaagc

1440 ccttcgagcg ggacatctcc accgagatct atcaggccgg cagcacccct tgtaacggcg

1500 tggaaggctt caactgctac ttcccactgc agtcctacgg ctttcagccc acaaatggcg

1560 tgggctatca gccctacaga gtggtggtgc tgagcttcga actgctgcat gcccctgcca

1620 cagtgtgcgg ccctaagaaa agcaccaatc tcgtgaagaa caaatgcgtg aacttcaact

1680 tcaacggcct gaccggcacc ggcgtgctga cagagagcaa caagaagttc ctgccattcc

1740 agcagtttgg ccgggatatc gccgatacca cagacgccgt tagagatccc cagacactgg

1800 aaatcctgga catcacccct tgcagcttcg gcggagtgtc tgtgatcacc cctggcacca

1860 acaccagcaa tcaggtggca gtgctgtacc aggacgtgaa ctgtaccgaa gtgcccgtgg

1920 ccattcacgc cgatcagctg acacctacat ggcgggtgta ctccaccggc agcaatgtgt

1980 ttcagaccag agccggctgt ctgatcggag ccgagcacgt gaacaatagc tacgagtgcg

2040 acatccccat cggcgctgga atctgcgcca gctaccagac acagacaaac agccctcgga

2100 gagccagaag cgtggccagc cagagcatca ttgcctacac aatgtctctg ggcgccgaga

2160 acagcgtggc ctactccaac aactctatcg ctatccccac caacttcacc atcagcgtga 2220 ccacagagat cctgcctgtg tccatgacca agaccagcgt ggactgcacc atgtacatct

2280 gcggcgattc caccgagtgc tccaacctgc tgctgcagta cggcagcttc tgcacccagc

2340 tgaatagagc cctgacaggg atcgccgtgg aacaggacaa gaacacccaa gaggtgttcg

2400 cccaagtgaa gcagatctac aagacccctc ctatcaagga cttcggcggc ttcaatttca

2460 gccagattct gcccgatcct agcaagccca gcaagcggag cttcatcgag gacctgctgt

2520 tcaacaaagt gacactggcc gacgccggct tcatcaagca gtatggcgat tgtctgggcg

2580 acattgccgc cagggatctg atttgcgccc agaagtttaa cggactgaca gtgctgcctc

2640 ctctgctgac cgatgagatg atcgcccagt acacatctgc cctgctggcc ggcacaatca

2700 caagcggctg gacatttgga gcaggcgccg ctctgcagat cccctttgct atgcagatgg

2760 cctaccggtt caacggcatc ggagtgaccc agaatgtgct gtacgagaac cagaagctga

2820 tcgccaacca gttcaacagc gccatcggca agatccagga cagcctgagc agcacagcaa

2880 gcgccctggg aaagctgcag gacgtggtca accagaatgc ccaggcactg aacaccctgg

2940 tcaagcagct gtcctccaac ttcggcgcca tcagctctgt gctgaacgat atcctgagca

3000 gactggaccc tcctgaggcc gaggtgcaga tcgacagact gatcacaggc agactgcaga

3060 gcctccagac atacgtgacc cagcagctga tcagagccgc cgagattaga gcctctgcca

3120 atctggccgc caccaagatg tctgagtgtg tgctgggcca gagcaagaga gtggactttt

3180 gcggcaaggg ctaccacctg atgagcttcc ctcagtctgc ccctcacggc gtggtgtttc

3240 tgcacgtgac atatgtgccc gctcaagaga agaatttcac caccgctcca gccatctgcc

3300 acgacggcaa agcccacttt cctagagaag gcgtgttcgt gtccaacggc acccattggt

3360 tcgtgacaca gcggaacttc tacgagcccc agatcatcac caccgacaac accttcgtgt

3420 ctggcaactg cgacgtcgtg atcggcattg tgaacaatac cgtgtacgac cctctgcagc

3480 ccgagctgga cagcttcaaa gaggaactgg acaagtactt taagaaccac acaagccccg

3540 acgtggacct gggcgatatc agcggaatca atgccagcgt cgtgaacatc cagaaagaga

3600 tcgaccggct gaacgaggtg gccaagaatc tgaacgagag cctgatcgac ctgcaagaac

3660 tggggaagta cgagcagtac atcaagtggc cctggtacat ctggctgggc tttatcgccg 3720 gactgattgc catcgtgatg gtcacaatca tgctgtgttg catgaccagc tgctgtagct

3780 gcctgaaggg ctgttgtagc tgtggcagct gctgcaagtt cgacgaggac gattctgagc

3840 ccgtgctgaa gggcgtgaaa ctgcactaca catgatgact cgagctggta ctgcatgcac

3900 gcaatgctag ctgccccttt cccgtcctgg gtaccccgag tctcccccga cctcgggtcc

3960 caggtatgct cccacctcca cctgccccac tcaccacctc tgctagttcc agacacctcc

4020 caagcacgca gcaatgcagc tcaaaacgct tagcctagcc acacccccac gggaaacagc

4080 agtgattaac ctttagcaat aaacgaaagt ttaactaagc tatactaacc ccagggttgg

4140 tcaatttcgt gccagccaca ccctggagct agcaaaaaaa aaaaaaaaaa aaaaaaaaaa

4200 aaagcatatg actaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaaaaaaaa aaa

4283

Sequence Number ( ID) : 21

Length : 1262

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .1262

> note, RBP020. 3 source, 1 . . 1262

> mol_type, other RNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgtttg 60 tgtttcttgt gctgctgcct cttgtgtctt ctcagtgtgt ggtgagattt ccaaatatta 120 caaatctgtg tccatttgga gaagtgttta atgcaacaag atttgcatct gtgtatgcat 180 ggaatagaaa aagaatttct aattgtgtgg ctgattattc tgtgctgtat aatagtgctt 240 ctttttccac atttaaatgt tatggagtgt ctccaacaaa attaaatgat ttatgtttta 300 caaatgtgta tgctgattct tttgtgatca gaggtgatga agtgagacag attgcccccg 360 gacagacagg aaaaattgct gattacaatt acaaactgcc tgatgatttt acaggatgtg 420 tgattgcttg gaattctaat aatttagatt ctaaagtggg aggaaattac aattatctgt 480 acagactgtt tagaaaatca aatctgaaac cttttgaaag agatatttca acagaaattt 540 atcaggctgg atcaacacct tgtaatggag tggaaggatt taattgttat tttccattac 600 agagctatgg atttcagcca accaatggtg tgggatatca gccatataga gtggtggtgc 660 tgtcttttga actgctgcat gcacctgcaa cagtgtgtgg acctaaaggc tcccccggct 720 ccggctccgg atctggttat attcctgaag ctccaagaga tgggcaagct tacgttcgta 780 aagatggcga atgggtatta ctttctacct ttttaggccg gtccctggag gtgctgttcc 840 agggccccgg ctgatgactc gagctggtac tgcatgcacg caatgctagc tgcccctttc 900 ccgtcctggg taccccgagt ctcccccgac ctcgggtccc aggtatgctc ccacctccac 960 ctgccccact caccacctct gctagttcca gacacctccc aagcacgcag caatgcagct

1020 caaaacgctt agcctagcca cacccccacg ggaaacagca gtgattaacc tttagcaata

1080 aacgaaagtt taactaagct atactaaccc cagggttggt caatttcgtg ccagccacac

1140 cctggagcta gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aagcatatga ctaaaaaaaa

1200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

1260 aa

1262

Sequence Number ( ID) : 22 Length : 1879 Molecule Type : AA Features Location/Qualifiers :

- REGION j 1 . . 1879

> note, Vi ral Protein

- source, 1 . . 1879

> mol_type, protein

> organism, synthetic construct Residues :

MEKVHVDI E E DSPF LRALQR SF PQF EVEAK QVTDNDHANA RAFSHLASKL I ETEVDPSDT 60

ILDIGSAPAR RMYSKHKYHC ICPMRCAEDP DRLYKYATKL KKNCKE ITDK E LDKKMKE LA 120

AVMSDPDLET ETMCLHDDES CRYEGQVAVY QDVYAVDGPT SLYHQANKGV RVAYWIGFDT 180

TPFMFKNLAG AYPSYSTNWA DETVLTARNI GLCSSDVME R SRRGMSI LRK KYLKPSNNVL 240

FSVGSTIYHE KRDLLRSWHL PSVFHLRGKQ NYTCRC ETIV SCDGYVVKRI AISPGLYGKP 300

SGYAATMHRE GF LCCKVTDT LNGERVSFPV CTYVPATLCD QMTGILATDV SADDAQKLLV 360

GLNQRIWNG RTQRNTNTMK NYLLPWAQA FARWAKEYKE DQEDERPLGL RDRQLVMGCC 420

IAIAF RRHKITS IYKRPDTQTI IKVNSDFHSF VLPRIGSNTL E IGLRTRIRK MLEEHKEPSP 480

LITAEDVQEA KCAADEAKEV REAE E LRAAL PPLAADVE E P TLEADVDLML QEAGAGSVET 540

PRGLIKVTSY AGEDKIGSYA VLSPQAVLKS EKLSCIHPLA EQVIVITHSG RKGRYAVEPY 600

HGKWVPEGH AIPVQDFQAL S ESATIVYNE RE FVNRYLHH IATHGGALNT DE EYYKTVKP 660

SEHDGEYLYD IDRKQCVKKE LVTGLGLTGE LVDPPFHE FA YESLRTRPAA PYQVPTIGVY 720

GVPGSGKSGI IKSAVTKKDL VVSAKKENCA E IIRDVKKMK GLDVNARTVD SVLLNGCKHP 780

VETLYIDEAF ACHAGTLRAL IAIIRPKKAV LCGDPKQCGF FNMMCLKVHF NHEICTQVFH 840

KSISRRCTKS VTSVVSTLFY DKKMRTTNPK ETKIVIDTTG STKPKQDDLI LTCF RGWVKQ 900

LQIDYKGNEI MTAAASQGLT RKGVYAVRYK VNENPLYAPT SEHVNVLLTR TEDRIVWKTL 960

AGDPWIKTLT AKYPGNFTAT I E EWQAEHDA IMRHI LERPD PTDVFQNKAN VCWAKALVPV

1020

LKTAGIDMTT EQWNTVDYF E TDKAHSAE IV LNQLCVRF FG LDLDSGLFSA PTVPLSIRNN

1080

HWDNSPSPNM YGLNKEWRQ LSRRYPQLPR AVATGRVYDM NTGTLRNYDP RINLVPVNRR

1140

LPHALVLHHN EHPQSDFSSF VSKLKGRTVL WGEKLSVPG KMVDWLSDRP EATF RARLDL

1200

GIPGDVPKYD IIFVNVRTPY KYHHYQQC ED HAIKLSMLTK KACLHLNPGG TCVSIGYGYA

1260

DRASESIIGA IARQFKFSRV CKPKSSL E ET EVL FVFIGYD RKARTHNPYK LSSTLTNIYT

1320

GSRLHEAGCA PSYHWRGDI ATATEGVIIN AANSKGQPGG GVCGALYKKF PESFDLQPIE 1380

VGKARLVKGA AKHIIHAVGP NFNKVSEVEG DKQLAEAYES IAKIVNDNNY KSVAIPLLST

1440

GIFSGNKDRL TQSLNHLLTA LDTTDADVAI YCRDKKWEMT LKEAVARREA VEEICISDDS

1500

SVTEPDAELV RVHPKSSLAG RKGYSTSDGK TFSYLEGTKF HQAAKDIAEI NAMWPVATEA

1560

NEQVCMYILG ESMSSIRSKC PVEESEASTP PSTLPCLCIH AMTPERVQRL KASRPEQITV

1620

CSSFPLPKYR ITGVQKIQCS QPILFSPKVP AYIHPRKYLV ETPPVDETPE PSAENQSTEG

1680

TPEQPPLITE DETRTRTPEP IIIEEEEEDS ISLLSDGPTH QVLQVEADIH GPPSVSSSSW

1740

SIPHASDFDV DSLSILDTLE GASVTSGATS AETNSYFAKS MEFLARPVPA PRTVFRNPPH

1800

PAPRTRTPSL APSRACSRTS LVSTPPGVNR VITREELEAL TPSRTPSRSV SRTSLVSNPP

1860

GVNRVITREE FEAFVAQQQ

1879

Sequence Number (ID): 23

Length: 613

Molecule Type: AA

Features Location/Qualifiers :

- REGION j 1..613

> note, Viral Protein

- source, 1. .613

> mol_type, protein

> organism, synthetic construct

Residues :

RFDAGAYIFS SDTGQGHLQQ KSVRQTVLSE WLERTELEI SYAPRLDQEK EELLRKKLQL 60

NPTPANRSRY QSRKVENMKA ITARRILQGL GHYLKAEGKV ECYRTLHPVP LYSSSVNRAF 120

SSPKVAVEAC NAMLKENFPT VASYCIIPEY DAYLDMVDGA SCCLDTASFC PAKLRSFPKK 180

HSYLEPTIRS AVPSAIQNTL QNVLAAATKR NCNVTQMREL PVLDSAAFNV ECFKKYACNN 240

EYWETFKENP IRLTEENWN YITKLKGPKA AALFAKTHNL NMLQDIPMDR FVMDLKRDVK 300

VTPGTKHTEE RPKVQVIQAA DPLATAYLCG IHRELVRRLN AVLLPNIHTL FDMSAEDFDA 360

IIAEHFQPGD CVLETDIASF DKSEDDAMAL TALMILEDLG VDAELLTLIE AAFGEISSIH 420

LPTKTKFKFG AMMKSGMFLT LFVNTVINIV IASRVLRERL TGSPCAAFIG DDNIVKGVKS 480

DKLMADRCAT WLNMEVKIID AWGEKAPYF CGGFILCDSV TGTACRVADP LKRLFKLGKP 540

LAADDEHDDD RRRALHEEST RWNRVGILSE LCKAVESRYE TVGTSIIVMA MTTLASSVKS 600

FSYLRGAPIT LYG 613

Sequence Number (ID): 24

Length: 11917

Molecule Type: RNA

Features Location/Qualifiers:

- misc_feature, 1..11917

> note, RBS004.1

- source, 1. .11917

> mol_type, other RNA > organism, synthetic construct

Residues : gatgggcggc gcatgagaga agcccagacc aattacctac ccaaaatgga gaaagttcac 60 gttgacatcg aggaagacag cccattcctc agagctttgc agcggagctt cccgcagttt 120 gaggtagaag ccaagcaggt cactgataat gaccatgcta atgccagagc gttttcgcat 180 ctggcttcaa aactgatcga aacggaggtg gacccatccg acacgatcct tgacattgga 240 agtgcgcccg cccgcagaat gtattctaag cacaagtatc attgtatctg tccgatgaga 300 tgtgcggaag atccggacag attgtataag tatgcaacta agctgaagaa aaactgtaag 360 gaaataactg ataaggaatt ggacaagaaa atgaaggagc tcgccgccgt catgagcgac 420 cctgacctgg aaactgagac tatgtgcctc cacgacgacg agtcgtgtcg ctacgaaggg 480 caagtcgctg tttaccagga tgtatacgcg gttgacggac cgacaagtct ctatcaccaa 540 gccaataagg gagttagagt cgcctactgg ataggctttg acaccacccc ttttatgttt 600 aagaacttgg ctggagcata tccatcatac tctaccaact gggccgacga aaccgtgtta 660 acggctcgta acataggcct atgcagctct gacgttatgg agcggtcacg tagagggatg 720 tccattctta gaaagaagta tttgaaacca tccaacaatg ttctattctc tgttggctcg 780 accatctacc acgaaaagag ggacttactg aggagctggc acctgccgtc tgtatttcac 840 ttacgtggca agcaaaatta cacatgtcgg tgtgagacta tagttagttg cgacgggtac 900 gtcgttaaaa gaatagctat cagtccaggc ctgtatggga agccttcagg ctatgctgct 960 acgatgcacc gcgagggatt cttgtgctgc aaagtgacag acacattgaa cggggagagg

1020 gtctcttttc ccgtgtgcac gtatgtgcca gctacattgt gtgaccaaat gactggcata

1080 ctggcaacag atgtcagtgc ggacgacgcg caaaaactgc tggttgggct caaccagcgt

1140 atagtcgtca acggtcgcac ccagagaaac accaatacca tgaaaaatta ccttttgccc

1200 gtagtggccc aggcatttgc taggtgggca aaggaatata aggaagatca agaagatgaa

1260 aggccactag gactacgaga tagacagtta gtcatggggt gttgttgggc ttttagaagg

1320 cacaagataa catctattta taagcgcccg gatacccaaa ccatcatcaa agtgaacagc

1380 gatttccact cattcgtgct gcccaggata ggcagtaaca cattggagat cgggctgaga

1440 acaagaatca ggaaaatgtt agaggagcac aaggagccgt cacctctcat taccgccgag

1500 gacgtacaag aagctaagtg cgcagccgat gaggctaagg aggtgcgtga agccgaggag

1560 ttgcgcgcag ctctaccacc tttggcagct gatgttgagg agcccactct ggaagccgat

1620 gtcgacttga tgttacaaga ggctggggcc ggctcagtgg agacacctcg tggcttgata

1680 aaggttacca gctacgctgg cgaggacaag atcggctctt acgctgtgct ttctccgcag

1740 gctgtactca agagtgaaaa attatcttgc atccaccctc tcgctgaaca agtcatagtg

1800 ataacacact ctggccgaaa agggcgttat gccgtggaac cataccatgg taaagtagtg

1860 gtgccagagg gacatgcaat acccgtccag gactttcaag ctctgagtga aagtgccacc

1920 attgtgtaca acgaacgtga gttcgtaaac aggtacctgc accatattgc cacacatgga

1980 ggagcgctga acactgatga agaatattac aaaactgtca agcccagcga gcacgacggc

2040 gaatacctgt acgacatcga caggaaacag tgcgtcaaga aagagctagt cactgggcta

2100 gggctcacag gcgagctggt cgatcctccc ttccatgaat tcgcctacga gagtctgaga

2160 acacgaccag ccgctcctta ccaagtacca accatagggg tgtatggcgt gccaggatca

2220 ggcaagtctg gcatcattaa aagcgcagtc accaaaaaag atctagtggt gagcgccaag

2280 aaagaaaact gtgcagaaat tataagggac gtcaagaaaa tgaaagggct ggacgtcaat

2340 gccagaactg tggactcagt gctcttgaat ggatgcaaac accccgtaga gaccctgtat

2400 attgacgagg cttttgcttg tcatgcaggt actctcagag cgctcatagc cattataaga

2460 cctaaaaagg cagtgctctg cggagatccc aaacagtgcg gtttttttaa catgatgtgc

2520 ctgaaagtgc attttaacca cgagatttgc acacaagtct tccacaaaag catctctcgc

2580 cgttgcacta aatctgtgac ttcggtcgtc tcaaccttgt tttacgacaa aaaaatgaga

2640 acgacgaatc cgaaagagac taagattgtg attgacacta ccggcagtac caaacctaag

2700 caggacgatc tcattctcac ttgtttcaga gggtgggtga agcagttgca aatagattac

2760 aaaggcaacg aaataatgac ggcagctgcc tctcaagggc tgacccgtaa aggtgtgtat

2820 gccgttcggt acaaggtgaa tgaaaatcct ctgtacgcac ccacctcaga acatgtgaac

2880 gtcctactga cccgcacgga ggaccgcatc gtgtggaaaa cactagccgg cgacccatgg

2940 ataaaaacac tgactgccaa gtaccctggg aatttcactg ccacgataga ggagtggcaa

3000 gcagagcatg atgccatcat gaggcacatc ttggagagac cggaccctac cgacgtcttc

3060 cagaataagg caaacgtgtg ttgggccaag gctttagtgc cggtgctgaa gaccgctggc

3120 atagacatga ccactgaaca atggaacact gtggattatt ttgaaacgga caaagctcac

3180 tcagcagaga tagtattgaa ccaactatgc gtgaggttct ttggactcga tctggactcc

3240 ggtctatttt ctgcacccac tgttccgtta tccattagga ataatcactg ggataactcc

3300 ccgtcgccta acatgtacgg gctgaataaa gaagtggtcc gtcagctctc tcgcaggtac

3360 ccacaactgc ctcgggcagt tgccactggt agagtctatg acatgaacac tggtacactg

3420 cgcaattatg atccgcgcat aaacctagta cctgtaaaca gaagactgcc tcatgcttta

3480 gtcctccacc ataatgaaca cccacagagt gacttttctt cattcgtcag caaattgaag

3540 ggcagaactg tcctggtggt cggggaaaag ttgtccgtcc caggcaaaat ggttgactgg

3600 ttgtcagacc ggcctgaggc taccttcaga gctcggctgg atttaggcat cccaggtgat

3660 gtgcccaaat atgacataat atttgttaat gtgaggaccc catataaata ccatcactat

3720 cagcagtgtg aagaccatgc cattaagcta agcatgttga ccaagaaagc atgtctgcat

3780 ctgaatcccg gcggaacctg tgtcagcata ggttatggtt acgctgacag ggccagcgaa

3840 agcatcattg gtgctatagc gcggcagttc aagttttccc gagtatgcaa accgaaatcc

3900 tcacttgagg agacggaagt tctgtttgta ttcattgggt acgatcgcaa ggcccgtacg

3960 cacaatcctt acaagctatc atcaaccttg accaacattt atacaggttc cagactccac

4020 gaagccggat gtgcaccctc atatcatgtg gtgcgagggg atattgccac ggccaccgaa

4080 ggagtgatta taaatgctgc taacagcaaa ggacaacctg gcggaggggt gtgcggagcg

4140 ctgtataaga aattcccgga aagtttcgat ttacagccga tcgaagtagg aaaagcgcga

4200 ctggtcaaag gtgcagctaa acatatcatt catgccgtag gaccaaactt caacaaagtt

4260 tcggaggttg aaggtgacaa acagttggca gaggcttatg agtccatcgc taagattgtc

4320 aacgataaca attacaagtc agtagcgatt ccactgttgt ccaccggcat cttttccggg

4380 aacaaagatc gactaaccca atcattgaac catttgctga cagctttaga caccactgat

4440 gcagatgtag ccatatactg cagggacaag aaatgggaaa tgactctcaa ggaagcagtg

4500 gctaggagag aagcagtgga ggagatatgc atatccgacg attcttcagt gacagaacct

4560 gatgcagagc tggtgagggt gcatcccaag agttctttgg ctggaaggaa gggctacagc

4620 acaagcgatg gcaaaacttt ctcatatttg gaagggacca agtttcacca ggcggccaag

4680 gatatagcag aaattaatgc catgtggccc gttgcaacgg aggccaatga gcaggtatgc

4740 atgtatatcc tcggagaaag catgagcagt attaggtcga aatgccccgt cgaggagtcg

4800 gaagcctcca caccacctag cacgctgcct tgcttgtgca tccatgccat gactccagaa

4860 agagtacagc gcctaaaagc ctcacgtcca gaacaaatta ctgtgtgctc atcctttcca

4920 ttgccgaagt atagaatcac tggtgtgcag aagatccaat gctcccagcc tatattgttc

4980 tcaccgaaag tgcctgcgta tattcatcca aggaagtatc tcgtggaaac accaccggta

5040 gacgagactc cggagccatc ggcagagaac caatccacag aggggacacc tgaacaacca

5100 ccacttataa ccgaggatga gaccaggact agaacgcctg agccgatcat catcgaagaa

5160 gaagaagaag atagcataag tttgctgtca gatggcccga cccaccaggt gctgcaagtc

5220 gaggcagaca ttcacgggcc gccctctgta tctagctcat cctggtccat tcctcatgca

5280 tccgactttg atgtggacag tttatccata cttgacaccc tggagggagc tagcgtgacc

5340 agcggggcaa cgtcagccga gactaactct tacttcgcaa agagtatgga gtttctggcg

5400 cgaccggtgc ctgcgcctcg aacagtattc aggaaccctc cacatcccgc tccgcgcaca

5460 agaacaccgt cacttgcacc cagcagggcc tgctccagaa ccagcctagt ttccaccccg

5520 ccaggcgtga atagggtgat cactagagag gagctcgaag cgcttacccc gtcacgcact

5580 cctagcaggt cggtctccag aaccagcctg gtctccaacc cgccaggcgt aaatagggtg

5640 attacaagag aggagtttga ggcgttcgta gcacaacaac aatgacggtt tgatgcgggt

5700 gcatacatct tttcctccga caccggtcaa gggcatttac aacaaaaatc agtaaggcaa

5760 acggtgctat ccgaagtggt gttggagagg accgaattgg agatttcgta tgccccgcgc

5820 ctcgaccaag aaaaagaaga attactacgc aagaaattac agttaaatcc cacacctgct

5880 aacagaagca gataccagtc caggaaggtg gagaacatga aagccataac agctagacgt

5940 attctgcaag gcctagggca ttatttgaag gcagaaggaa aagtggagtg ctaccgaacc

6000 ctgcatcctg ttcctttgta ttcatctagt gtgaaccgtg ccttttcaag ccccaaggtc

6060 gcagtggaag cctgtaacgc catgttgaaa gagaactttc cgactgtggc ttcttactgt

6120 attattccag agtacgatgc ctatttggac atggttgacg gagcttcatg ctgcttagac

6180 actgccagtt tttgccctgc aaagctgcgc agctttccaa agaaacactc ctatttggaa

6240 cccacaatac gatcggcagt gccttcagcg atccagaaca cgctccagaa cgtcctggca

6300 gctgccacaa aaagaaattg caatgtcacg caaatgagag aattgcccgt attggattcg

6360 gcggccttta atgtggaatg cttcaagaaa tatgcgtgta ataatgaata ttgggaaacg

6420 tttaaagaaa accccatcag gcttactgaa gaaaacgtgg taaattacat taccaaatta

6480 aaaggaccaa aagctgctgc tctttttgcg aagacacata atttgaatat gttgcaggac

6540 ataccaatgg acaggtttgt aatggactta aagagagacg tgaaagtgac tccaggaaca

6600 aaacatactg aagaacggcc caaggtacag gtgatccagg ctgccgatcc gctagcaaca

6660 gcgtatctgt gcggaatcca ccgagagctg gttaggagat taaatgcggt cctgcttccg

6720 aacattcata cactgtttga tatgtcggct gaagactttg acgctattat agccgagcac

6780 ttccagcctg gggattgtgt tctggaaact gacatcgcgt cgtttgataa aagtgaggac

6840 gacgccatgg ctctgaccgc gttaatgatt ctggaagact taggtgtgga cgcagagctg

6900 ttgacgctga ttgaggcggc tttcggcgaa atttcatcaa tacatttgcc cactaaaact

6960 aaatttaaat tcggagccat gatgaaatct ggaatgttcc tcacactgtt tgtgaacaca

7020 gtcattaaca ttgtaatcgc aagcagagtg ttgagagaac ggctaaccgg atcaccatgt

7080 gcagcattca ttggagatga caatatcgtg aaaggagtca aatcggacaa attaatggca

7140 gacaggtgcg ccacctggtt gaatatggaa gtcaagatta tagatgctgt ggtgggcgag

7200 aaagcgcctt atttctgtgg agggtttatt ttgtgtgact ccgtgaccgg cacagcgtgc

7260 cgtgtggcag accccctaaa aaggctgttt aagctaggca aacctctggc agcagacgat

7320 gaacatgatg atgacaggag aagggcattg catgaggagt caacacgctg gaaccgagtg

7380 ggtattcttt cagagctgtg caaggcagta gaatcaaggt atgaaaccgt aggaacttcc

7440 atcatagtta tggccatgac tactctagct agcagtgtta aatcattcag ctacctgaga

7500 ggggccccta taactctcta cggctaacct gaatggacta cgacatagtc tagtccgcca

7560 agactagtat gtttgtgttt cttgtgctgc tgcctcttgt gtcttctcag tgtgtgaatt

7620 tgacaacaag aacacagctg ccaccagctt atacaaattc ttttaccaga ggagtgtatt

7680 atcctgataa agtgtttaga tcttctgtgc tgcacagcac acaggacctg tttctgccat

7740 tttttagcaa tgtgacatgg tttcatgcaa ttcatgtgtc tggaacaaat ggaacaaaaa

7800 gatttgataa tcctgtgctg ccttttaatg atggagtgta ttttgcttca acagaaaagt

7860 caaatattat tagaggatgg atttttggaa caacactgga ttctaaaaca cagtctctgc

7920 tgattgtgaa taatgcaaca aatgtggtga ttaaagtgtg tgaatttcag ttttgtaatg

7980 atccttttct gggagtgtat tatcacaaaa ataataaatc ttggatggaa tctgaattta

8040 gagtgtattc ctctgcaaat aattgtacat ttgaatatgt gtctcagcct tttctgatgg

8100 atctggaagg aaaacagggc aattttaaaa atctgagaga atttgtgttt aaaaatattg

8160 atggatattt taaaatttat tctaaacaca caccaattaa tttagtgaga gatctgcctc

8220 agggattttc tgctctggaa cctctggtgg atctgccaat tggcattaat attacaagat

8280 ttcagacact gctggctctg cacagatctt atctgacacc tggagattct tcttctggat

8340 ggacagccgg agctgcagct tattatgtgg gctatctgca gccaagaaca tttctgctga

8400 aatataatga aaatggaaca attacagatg ctgtggattg tgctctggat cctctgtctg

8460 aaacaaaatg tacattaaaa tcttttacag tggaaaaagg catttatcag acatctaatt

8520 ttagagtgca gccaacagaa tctattgtga gatttccaaa tattacaaat ctgtgtccat

8580 ttggagaagt gtttaatgca acaagatttg catctgtgta tgcatggaat agaaaaagaa

8640 tttctaattg tgtggctgat tattctgtgc tgtataatag tgcttctttt tccacattta

8700 aatgttatgg agtgtctcca acaaaattaa atgatttatg ttttacaaat gtgtatgctg

8760 attcttttgt gatcagaggt gatgaagtga gacagattgc ccccggacag acaggaaaaa

8820 ttgctgatta caattacaaa ctgcctgatg attttacagg atgtgtgatt gcttggaatt

8880 ctaataattt agattctaaa gtgggaggaa attacaatta tctgtacaga ctgtttagaa

8940 aatcaaatct gaaacctttt gaaagagata tttcaacaga aatttatcag gctggatcaa

9000 caccttgtaa tggagtggaa ggatttaatt gttattttcc attacagagc tatggatttc

9060 agccaaccaa tggtgtggga tatcagccat atagagtggt ggtgctgtct tttgaactgc

9120 tgcatgcacc tgcaacagtg tgtggaccta aaaaatctac aaatttagtg aaaaataaat

9180 gtgtgaattt taattttaat ggattaacag gaacaggagt gctgacagaa tctaataaaa

9240 aatttctgcc ttttcagcag tttggcagag atattgcaga taccacagat gcagtgagag

9300 atcctcagac attagaaatt ctggatatta caccttgttc ttttgggggt gtgtctgtga

9360 ttacacctgg aacaaataca tctaatcagg tggctgtgct gtatcaggat gtgaattgta

9420 cagaagtgcc agtggcaatt catgcagatc agctgacacc aacatggaga gtgtattcta

9480 caggatctaa tgtgtttcag acaagagcag gatgtctgat tggagcagaa catgtgaata

9540 attcttatga atgtgatatt ccaattggag caggcatttg tgcatcttat cagacacaga

9600 caaattcccc aaggagagca agatctgtgg catctcagtc tattattgca tacaccatgt

9660 ctctgggagc agaaaattct gtggcatatt ctaataattc tattgctatt ccaacaaatt

9720 ttaccatttc tgtgacaaca gaaattttac ctgtgtctat gacaaaaaca tctgtggatt

9780 gtaccatgta catttgtgga gattctacag aatgttctaa tctgctgctg cagtatggat

9840 ctttttgtac acagctgaat agagctttaa caggaattgc tgtggaacag gataaaaata

9900 cacaggaagt gtttgctcag gtgaaacaga tttacaaaac accaccaatt aaagattttg

9960 gaggatttaa ttttagccag attctgcctg atccttctaa accttctaaa agatctttta

10020 ttgaagatct gctgtttaat aaagtgacac tggcagatgc aggatttatt aaacagtatg

10080 gagattgcct gggtgatatt gctgcaagag atctgatttg tgctcagaaa tttaatggac

10140 tgacagtgct gcctcctctg ctgacagatg aaatgattgc tcagtacaca tctgctttac

10200 tggctggaac aattacaagc ggatggacat ttggagctgg agctgctctg cagattcctt

10260 ttgcaatgca gatggcttac agatttaatg gaattggagt gacacagaat gtgttatatg

10320 aaaatcagaa actgattgca aatcagttta attctgcaat tggcaaaatt caggattctc

10380 tgtcttctac agcttctgct ctgggaaaac tgcaggatgt ggtgaatcag aatgcacagg

10440 cactgaatac tctggtgaaa cagctgtcta gcaattttgg ggcaatttct tctgtgctga

10500 atgatattct gtctagactg gatcctcctg aagctgaagt gcagattgat agactgatca

10560 caggaagact gcagtctctg cagacttatg tgacacagca gctgattaga gctgctgaaa

10620 ttagagcttc tgctaatctg gctgctacaa aaatgtctga atgtgtgctg ggacagtcaa

10680 aaagagtgga tttttgtgga aaaggatatc atctgatgtc ttttccacag tctgctccac

10740 atggagtggt gtttttacat gtgacatatg tgccagcaca ggaaaagaat tttaccacag

10800 caccagcaat ttgtcatgat ggaaaagcac attttccaag agaaggagtg tttgtgtcta

10860 atggaacaca ttggtttgtg acacagagaa atttttatga acctcagatt attacaacag

10920 ataatacatt tgtgtcagga aattgtgatg tggtgattgg aattgtgaat aatacagtgt

10980 atgatccact gcagccagaa ctggattctt ttaaagaaga actggataaa tattttaaaa

11040 atcacacatc tcctgatgtg gatttaggag atatttctgg aatcaatgca tctgtggtga

11100 atattcagaa agaaattgat agactgaatg aagtggccaa aaatctgaat gaatctctga

11160 ttgatctgca ggaacttgga aaatatgaac agtacattaa atggccttgg tacatttggc

11220 ttggatttat tgcaggatta attgcaattg tgatggtgac aattatgtta tgttgtatga

11280 catcatgttg ttcttgttta aaaggatgtt gttcttgtgg aagctgttgt aaatttgatg

11340 aagatgattc tgaacctgtg ttaaaaggag tgaaattgca ttacacatga tgactcgagc

11400 tggtactgca tgcacgcaat gctagctgcc cctttcccgt cctgggtacc ccgagtctcc

11460 cccgacctcg ggtcccaggt atgctcccac ctccacctgc cccactcacc acctctgcta

11520 gttccagaca cctcccaagc acgcagcaat gcagctcaaa acgcttagcc tagccacacc

11580 cccacgggaa acagcagtga ttaaccttta gcaataaacg aaagtttaac taagctatac

11640 taaccccagg gttggtcaat ttcgtgccag ccacaccgcg gccgcatgaa tacagcagca

11700 attggcaagc tgcttacata gaactcgcgg cgattggcat gccgccttaa aatttttatt

11760 ttattttttc ttttcttttc cgaatcggat tttgttttta atatttcaaa aaaaaaaaaa

11820 aaaaaaaaaa aaaaaaagca tatgactaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

11880 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa

11917

Sequence Number (ID) : 25

Length : 11917

Molecule Type : RNA

Features Location/Qualif iers :

- misc_feature, 1. .11917

> note, RBS004.2

- source, 1. .11917

> mol_type, other RNA

> organism, synthetic construct Residues : gatgggcggc gcatgagaga agcccagacc aattacctac ccaaaatgga gaaagttcac 60 gttgacatcg aggaagacag cccattcctc agagctttgc agcggagctt cccgcagttt 120 gaggtagaag ccaagcaggt cactgataat gaccatgcta atgccagagc gttttcgcat 180 ctggcttcaa aactgatcga aacggaggtg gacccatccg acacgatcct tgacattgga 240 agtgcgcccg cccgcagaat gtattctaag cacaagtatc attgtatctg tccgatgaga 300 tgtgcggaag atccggacag attgtataag tatgcaacta agctgaagaa aaactgtaag 360 gaaataactg ataaggaatt ggacaagaaa atgaaggagc tcgccgccgt catgagcgac 420 cctgacctgg aaactgagac tatgtgcctc cacgacgacg agtcgtgtcg ctacgaaggg 480 caagtcgctg tttaccagga tgtatacgcg gttgacggac cgacaagtct ctatcaccaa 540 gccaataagg gagttagagt cgcctactgg ataggctttg acaccacccc ttttatgttt 600 aagaacttgg ctggagcata tccatcatac tctaccaact gggccgacga aaccgtgtta 660 acggctcgta acataggcct atgcagctct gacgttatgg agcggtcacg tagagggatg 720 tccattctta gaaagaagta tttgaaacca tccaacaatg ttctattctc tgttggctcg 780 accatctacc acgaaaagag ggacttactg aggagctggc acctgccgtc tgtatttcac 840 ttacgtggca agcaaaatta cacatgtcgg tgtgagacta tagttagttg cgacgggtac 900 gtcgttaaaa gaatagctat cagtccaggc ctgtatggga agccttcagg ctatgctgct 960 acgatgcacc gcgagggatt cttgtgctgc aaagtgacag acacattgaa cggggagagg

1020 gtctcttttc ccgtgtgcac gtatgtgcca gctacattgt gtgaccaaat gactggcata

1080 ctggcaacag atgtcagtgc ggacgacgcg caaaaactgc tggttgggct caaccagcgt

1140 atagtcgtca acggtcgcac ccagagaaac accaatacca tgaaaaatta ccttttgccc

1200 gtagtggccc aggcatttgc taggtgggca aaggaatata aggaagatca agaagatgaa

1260 aggccactag gactacgaga tagacagtta gtcatggggt gttgttgggc ttttagaagg

1320 cacaagataa catctattta taagcgcccg gatacccaaa ccatcatcaa agtgaacagc

1380 gatttccact cattcgtgct gcccaggata ggcagtaaca cattggagat cgggctgaga

1440 acaagaatca ggaaaatgtt agaggagcac aaggagccgt cacctctcat taccgccgag

1500 gacgtacaag aagctaagtg cgcagccgat gaggctaagg aggtgcgtga agccgaggag

1560 ttgcgcgcag ctctaccacc tttggcagct gatgttgagg agcccactct ggaagccgat

1620 gtcgacttga tgttacaaga ggctggggcc ggctcagtgg agacacctcg tggcttgata

1680 aaggttacca gctacgctgg cgaggacaag atcggctctt acgctgtgct ttctccgcag

1740 gctgtactca agagtgaaaa attatcttgc atccaccctc tcgctgaaca agtcatagtg

1800 ataacacact ctggccgaaa agggcgttat gccgtggaac cataccatgg taaagtagtg

1860 gtgccagagg gacatgcaat acccgtccag gactttcaag ctctgagtga aagtgccacc

1920 attgtgtaca acgaacgtga gttcgtaaac aggtacctgc accatattgc cacacatgga

1980 ggagcgctga acactgatga agaatattac aaaactgtca agcccagcga gcacgacggc

2040 gaatacctgt acgacatcga caggaaacag tgcgtcaaga aagagctagt cactgggcta

2100 gggctcacag gcgagctggt cgatcctccc ttccatgaat tcgcctacga gagtctgaga 2160 acacgaccag ccgctcctta ccaagtacca accatagggg tgtatggcgt gccaggatca

2220 ggcaagtctg gcatcattaa aagcgcagtc accaaaaaag atctagtggt gagcgccaag

2280 aaagaaaact gtgcagaaat tataagggac gtcaagaaaa tgaaagggct ggacgtcaat

2340 gccagaactg tggactcagt gctcttgaat ggatgcaaac accccgtaga gaccctgtat

2400 attgacgagg cttttgcttg tcatgcaggt actctcagag cgctcatagc cattataaga

2460 cctaaaaagg cagtgctctg cggagatccc aaacagtgcg gtttttttaa catgatgtgc

2520 ctgaaagtgc attttaacca cgagatttgc acacaagtct tccacaaaag catctctcgc

2580 cgttgcacta aatctgtgac ttcggtcgtc tcaaccttgt tttacgacaa aaaaatgaga

2640 acgacgaatc cgaaagagac taagattgtg attgacacta ccggcagtac caaacctaag

2700 caggacgatc tcattctcac ttgtttcaga gggtgggtga agcagttgca aatagattac

2760 aaaggcaacg aaataatgac ggcagctgcc tctcaagggc tgacccgtaa aggtgtgtat

2820 gccgttcggt acaaggtgaa tgaaaatcct ctgtacgcac ccacctcaga acatgtgaac

2880 gtcctactga cccgcacgga ggaccgcatc gtgtggaaaa cactagccgg cgacccatgg

2940 ataaaaacac tgactgccaa gtaccctggg aatttcactg ccacgataga ggagtggcaa

3000 gcagagcatg atgccatcat gaggcacatc ttggagagac cggaccctac cgacgtcttc

3060 cagaataagg caaacgtgtg ttgggccaag gctttagtgc cggtgctgaa gaccgctggc

3120 atagacatga ccactgaaca atggaacact gtggattatt ttgaaacgga caaagctcac

3180 tcagcagaga tagtattgaa ccaactatgc gtgaggttct ttggactcga tctggactcc

3240 ggtctatttt ctgcacccac tgttccgtta tccattagga ataatcactg ggataactcc

3300 ccgtcgccta acatgtacgg gctgaataaa gaagtggtcc gtcagctctc tcgcaggtac

3360 ccacaactgc ctcgggcagt tgccactggt agagtctatg acatgaacac tggtacactg

3420 cgcaattatg atccgcgcat aaacctagta cctgtaaaca gaagactgcc tcatgcttta

3480 gtcctccacc ataatgaaca cccacagagt gacttttctt cattcgtcag caaattgaag

3540 ggcagaactg tcctggtggt cggggaaaag ttgtccgtcc caggcaaaat ggttgactgg

3600 ttgtcagacc ggcctgaggc taccttcaga gctcggctgg atttaggcat cccaggtgat 3660 gtgcccaaat atgacataat atttgttaat gtgaggaccc catataaata ccatcactat

3720 cagcagtgtg aagaccatgc cattaagcta agcatgttga ccaagaaagc atgtctgcat

3780 ctgaatcccg gcggaacctg tgtcagcata ggttatggtt acgctgacag ggccagcgaa

3840 agcatcattg gtgctatagc gcggcagttc aagttttccc gagtatgcaa accgaaatcc

3900 tcacttgagg agacggaagt tctgtttgta ttcattgggt acgatcgcaa ggcccgtacg

3960 cacaatcctt acaagctatc atcaaccttg accaacattt atacaggttc cagactccac

4020 gaagccggat gtgcaccctc atatcatgtg gtgcgagggg atattgccac ggccaccgaa

4080 ggagtgatta taaatgctgc taacagcaaa ggacaacctg gcggaggggt gtgcggagcg

4140 ctgtataaga aattcccgga aagtttcgat ttacagccga tcgaagtagg aaaagcgcga

4200 ctggtcaaag gtgcagctaa acatatcatt catgccgtag gaccaaactt caacaaagtt

4260 tcggaggttg aaggtgacaa acagttggca gaggcttatg agtccatcgc taagattgtc

4320 aacgataaca attacaagtc agtagcgatt ccactgttgt ccaccggcat cttttccggg

4380 aacaaagatc gactaaccca atcattgaac catttgctga cagctttaga caccactgat

4440 gcagatgtag ccatatactg cagggacaag aaatgggaaa tgactctcaa ggaagcagtg

4500 gctaggagag aagcagtgga ggagatatgc atatccgacg attcttcagt gacagaacct

4560 gatgcagagc tggtgagggt gcatcccaag agttctttgg ctggaaggaa gggctacagc

4620 acaagcgatg gcaaaacttt ctcatatttg gaagggacca agtttcacca ggcggccaag

4680 gatatagcag aaattaatgc catgtggccc gttgcaacgg aggccaatga gcaggtatgc

4740 atgtatatcc tcggagaaag catgagcagt attaggtcga aatgccccgt cgaggagtcg

4800 gaagcctcca caccacctag cacgctgcct tgcttgtgca tccatgccat gactccagaa

4860 agagtacagc gcctaaaagc ctcacgtcca gaacaaatta ctgtgtgctc atcctttcca

4920 ttgccgaagt atagaatcac tggtgtgcag aagatccaat gctcccagcc tatattgttc

4980 tcaccgaaag tgcctgcgta tattcatcca aggaagtatc tcgtggaaac accaccggta

5040 gacgagactc cggagccatc ggcagagaac caatccacag aggggacacc tgaacaacca

5100 ccacttataa ccgaggatga gaccaggact agaacgcctg agccgatcat catcgaagaa 5160 gaagaagaag atagcataag tttgctgtca gatggcccga cccaccaggt gctgcaagtc

5220 gaggcagaca ttcacgggcc gccctctgta tctagctcat cctggtccat tcctcatgca

5280 tccgactttg atgtggacag tttatccata cttgacaccc tggagggagc tagcgtgacc

5340 agcggggcaa cgtcagccga gactaactct tacttcgcaa agagtatgga gtttctggcg

5400 cgaccggtgc ctgcgcctcg aacagtattc aggaaccctc cacatcccgc tccgcgcaca

5460 agaacaccgt cacttgcacc cagcagggcc tgctccagaa ccagcctagt ttccaccccg

5520 ccaggcgtga atagggtgat cactagagag gagctcgaag cgcttacccc gtcacgcact

5580 cctagcaggt cggtctccag aaccagcctg gtctccaacc cgccaggcgt aaatagggtg

5640 attacaagag aggagtttga ggcgttcgta gcacaacaac aatgacggtt tgatgcgggt

5700 gcatacatct tttcctccga caccggtcaa gggcatttac aacaaaaatc agtaaggcaa

5760 acggtgctat ccgaagtggt gttggagagg accgaattgg agatttcgta tgccccgcgc

5820 ctcgaccaag aaaaagaaga attactacgc aagaaattac agttaaatcc cacacctgct

5880 aacagaagca gataccagtc caggaaggtg gagaacatga aagccataac agctagacgt

5940 attctgcaag gcctagggca ttatttgaag gcagaaggaa aagtggagtg ctaccgaacc

6000 ctgcatcctg ttcctttgta ttcatctagt gtgaaccgtg ccttttcaag ccccaaggtc

6060 gcagtggaag cctgtaacgc catgttgaaa gagaactttc cgactgtggc ttcttactgt

6120 attattccag agtacgatgc ctatttggac atggttgacg gagcttcatg ctgcttagac

6180 actgccagtt tttgccctgc aaagctgcgc agctttccaa agaaacactc ctatttggaa

6240 cccacaatac gatcggcagt gccttcagcg atccagaaca cgctccagaa cgtcctggca

6300 gctgccacaa aaagaaattg caatgtcacg caaatgagag aattgcccgt attggattcg

6360 gcggccttta atgtggaatg cttcaagaaa tatgcgtgta ataatgaata ttgggaaacg

6420 tttaaagaaa accccatcag gcttactgaa gaaaacgtgg taaattacat taccaaatta

6480 aaaggaccaa aagctgctgc tctttttgcg aagacacata atttgaatat gttgcaggac

6540 ataccaatgg acaggtttgt aatggactta aagagagacg tgaaagtgac tccaggaaca

6600 aaacatactg aagaacggcc caaggtacag gtgatccagg ctgccgatcc gctagcaaca 6660 gcgtatctgt gcggaatcca ccgagagctg gttaggagat taaatgcggt cctgcttccg

6720 aacattcata cactgtttga tatgtcggct gaagactttg acgctattat agccgagcac

6780 ttccagcctg gggattgtgt tctggaaact gacatcgcgt cgtttgataa aagtgaggac

6840 gacgccatgg ctctgaccgc gttaatgatt ctggaagact taggtgtgga cgcagagctg

6900 ttgacgctga ttgaggcggc tttcggcgaa atttcatcaa tacatttgcc cactaaaact

6960 aaatttaaat tcggagccat gatgaaatct ggaatgttcc tcacactgtt tgtgaacaca

7020 gtcattaaca ttgtaatcgc aagcagagtg ttgagagaac ggctaaccgg atcaccatgt

7080 gcagcattca ttggagatga caatatcgtg aaaggagtca aatcggacaa attaatggca

7140 gacaggtgcg ccacctggtt gaatatggaa gtcaagatta tagatgctgt ggtgggcgag

7200 aaagcgcctt atttctgtgg agggtttatt ttgtgtgact ccgtgaccgg cacagcgtgc

7260 cgtgtggcag accccctaaa aaggctgttt aagctaggca aacctctggc agcagacgat

7320 gaacatgatg atgacaggag aagggcattg catgaggagt caacacgctg gaaccgagtg

7380 ggtattcttt cagagctgtg caaggcagta gaatcaaggt atgaaaccgt aggaacttcc

7440 atcatagtta tggccatgac tactctagct agcagtgtta aatcattcag ctacctgaga

7500 ggggccccta taactctcta cggctaacct gaatggacta cgacatagtc tagtccgcca

7560 agactagtat gttcgtgttc ctggtgctgc tgcctctggt gtccagccag tgtgtgaacc

7620 tgaccaccag aacacagctg cctccagcct acaccaacag ctttaccaga ggcgtgtact

7680 accccgacaa ggtgttcaga tccagcgtgc tgcactctac ccaggacctg ttcctgcctt

7740 tcttcagcaa cgtgacctgg ttccacgcca tccacgtgtc cggcaccaat ggcaccaaga

7800 gattcgacaa ccccgtgctg cccttcaacg acggggtgta ctttgccagc accgagaagt

7860 ccaacatcat cagaggctgg atcttcggca ccacactgga cagcaagacc cagagcctgc

7920 tgatcgtgaa caacgccacc aacgtggtca tcaaagtgtg cgagttccag ttctgcaacg

7980 accccttcct gggcgtctac taccacaaga acaacaagag ctggatggaa agcgagttcc

8040 gggtgtacag cagcgccaac aactgcacct tcgagtacgt gtcccagcct ttcctgatgg

8100 acctggaagg caagcagggc aacttcaaga acctgcgcga gttcgtgttt aagaacatcg 8160 acggctactt caagatctac agcaagcaca cccctatcaa cctcgtgcgg gatctgcctc

8220 agggcttctc tgctctggaa cccctggtgg atctgcccat cggcatcaac atcacccggt

8280 ttcagacact gctggccctg cacagaagct acctgacacc tggcgatagc agcagcggat

8340 ggacagctgg tgccgccgct tactatgtgg gctacctgca gcctagaacc ttcctgctga

8400 agtacaacga gaacggcacc atcaccgacg ccgtggattg tgctctggat cctctgagcg

8460 agacaaagtg caccctgaag tccttcaccg tggaaaaggg catctaccag accagcaact

8520 tccgggtgca gcccaccgaa tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct

8580 tcggcgaggt gttcaatgcc accagattcg cctctgtgta cgcctggaac cggaagcgga

8640 tcagcaattg cgtggccgac tactccgtgc tgtacaactc cgccagcttc agcaccttca

8700 agtgctacgg cgtgtcccct accaagctga acgacctgtg cttcacaaac gtgtacgccg

8760 acagcttcgt gatccgggga gatgaagtgc ggcagattgc ccctggacag acaggcaaga

8820 tcgccgacta caactacaag ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca

8880 gcaacaacct ggactccaaa gtcggcggca actacaatta cctgtaccgg ctgttccgga

8940 agtccaatct gaagcccttc gagcgggaca tctccaccga gatctatcag gccggcagca

9000 ccccttgtaa cggcgtggaa ggcttcaact gctacttccc actgcagtcc tacggctttc

9060 agcccacaaa tggcgtgggc tatcagccct acagagtggt ggtgctgagc ttcgaactgc

9120 tgcatgcccc tgccacagtg tgcggcccta agaaaagcac caatctcgtg aagaacaaat

9180 gcgtgaactt caacttcaac ggcctgaccg gcaccggcgt gctgacagag agcaacaaga

9240 agttcctgcc attccagcag tttggccggg atatcgccga taccacagac gccgttagag

9300 atccccagac actggaaatc ctggacatca ccccttgcag cttcggcgga gtgtctgtga

9360 tcacccctgg caccaacacc agcaatcagg tggcagtgct gtaccaggac gtgaactgta

9420 ccgaagtgcc cgtggccatt cacgccgatc agctgacacc tacatggcgg gtgtactcca

9480 ccggcagcaa tgtgtttcag accagagccg gctgtctgat cggagccgag cacgtgaaca

9540 atagctacga gtgcgacatc cccatcggcg ctggaatctg cgccagctac cagacacaga

9600 caaacagccc tcggagagcc agaagcgtgg ccagccagag catcattgcc tacacaatgt 9660 ctctgggcgc cgagaacagc gtggcctact ccaacaactc tatcgctatc cccaccaact

9720 tcaccatcag cgtgaccaca gagatcctgc ctgtgtccat gaccaagacc agcgtggact

9780 gcaccatgta catctgcggc gattccaccg agtgctccaa cctgctgctg cagtacggca

9840 gcttctgcac ccagctgaat agagccctga cagggatcgc cgtggaacag gacaagaaca

9900 cccaagaggt gttcgcccaa gtgaagcaga tctacaagac ccctcctatc aaggacttcg

9960 gcggcttcaa tttcagccag attctgcccg atcctagcaa gcccagcaag cggagcttca

10020 tcgaggacct gctgttcaac aaagtgacac tggccgacgc cggcttcatc aagcagtatg

10080 gcgattgtct gggcgacatt gccgccaggg atctgatttg cgcccagaag tttaacggac

10140 tgacagtgct gcctcctctg ctgaccgatg agatgatcgc ccagtacaca tctgccctgc

10200 tggccggcac aatcacaagc ggctggacat ttggagcagg cgccgctctg cagatcccct

10260 ttgctatgca gatggcctac cggttcaacg gcatcggagt gacccagaat gtgctgtacg

10320 agaaccagaa gctgatcgcc aaccagttca acagcgccat cggcaagatc caggacagcc

10380 tgagcagcac agcaagcgcc ctgggaaagc tgcaggacgt ggtcaaccag aatgcccagg

10440 cactgaacac cctggtcaag cagctgtcct ccaacttcgg cgccatcagc tctgtgctga

10500 acgatatcct gagcagactg gaccctcctg aggccgaggt gcagatcgac agactgatca

10560 caggcagact gcagagcctc cagacatacg tgacccagca gctgatcaga gccgccgaga

10620 ttagagcctc tgccaatctg gccgccacca agatgtctga gtgtgtgctg ggccagagca

10680 agagagtgga cttttgcggc aagggctacc acctgatgag cttccctcag tctgcccctc

10740 acggcgtggt gtttctgcac gtgacatatg tgcccgctca agagaagaat ttcaccaccg

10800 ctccagccat ctgccacgac ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca

10860 acggcaccca ttggttcgtg acacagcgga acttctacga gccccagatc atcaccaccg

10920 acaacacctt cgtgtctggc aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt

10980 acgaccctct gcagcccgag ctggacagct tcaaagagga actggacaag tactttaaga

11040 accacacaag ccccgacgtg gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga

11100 acatccagaa agagatcgac cggctgaacg aggtggccaa gaatctgaac gagagcctga 11160 tcgacctgca agaactgggg aagtacgagc agtacatcaa gtggccctgg tacatctggc

11220 tgggctttat cgccggactg attgccatcg tgatggtcac aatcatgctg tgttgcatga

11280 ccagctgctg tagctgcctg aagggctgtt gtagctgtgg cagctgctgc aagttcgacg

11340 aggacgattc tgagcccgtg ctgaagggcg tgaaactgca ctacacatga tgactcgagc

11400 tggtactgca tgcacgcaat gctagctgcc cctttcccgt cctgggtacc ccgagtctcc

11460 cccgacctcg ggtcccaggt atgctcccac ctccacctgc cccactcacc acctctgcta

11520 gttccagaca cctcccaagc acgcagcaat gcagctcaaa acgcttagcc tagccacacc

11580 cccacgggaa acagcagtga ttaaccttta gcaataaacg aaagtttaac taagctatac

11640 taaccccagg gttggtcaat ttcgtgccag ccacaccgcg gccgcatgaa tacagcagca

11700 attggcaagc tgcttacata gaactcgcgg cgattggcat gccgccttaa aatttttatt

11760 ttattttttc ttttcttttc cgaatcggat tttgttttta atatttcaaa aaaaaaaaaa

11820 aaaaaaaaaa aaaaaaagca tatgactaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

11880 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa

11917

Sequence Number (ID) : 26

Length : 8896

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .8896

> note, RBS004.3

- source, 1. .8896

> mol_type, other RNA

> organism, synthetic construct Residues : gatgggcggc gcatgagaga agcccagacc aattacctac ccaaaatgga gaaagttcac 60 gttgacatcg aggaagacag cccattcctc agagctttgc agcggagctt cccgcagttt 120 gaggtagaag ccaagcaggt cactgataat gaccatgcta atgccagagc gttttcgcat 180 ctggcttcaa aactgatcga aacggaggtg gacccatccg acacgatcct tgacattgga 240 agtgcgcccg cccgcagaat gtattctaag cacaagtatc attgtatctg tccgatgaga 300 tgtgcggaag atccggacag attgtataag tatgcaacta agctgaagaa aaactgtaag 360 gaaataactg ataaggaatt ggacaagaaa atgaaggagc tcgccgccgt catgagcgac 420 cctgacctgg aaactgagac tatgtgcctc cacgacgacg agtcgtgtcg ctacgaaggg 480 caagtcgctg tttaccagga tgtatacgcg gttgacggac cgacaagtct ctatcaccaa 540 gccaataagg gagttagagt cgcctactgg ataggctttg acaccacccc ttttatgttt 600 aagaacttgg ctggagcata tccatcatac tctaccaact gggccgacga aaccgtgtta 660 acggctcgta acataggcct atgcagctct gacgttatgg agcggtcacg tagagggatg 720 tccattctta gaaagaagta tttgaaacca tccaacaatg ttctattctc tgttggctcg 780 accatctacc acgaaaagag ggacttactg aggagctggc acctgccgtc tgtatttcac 840 ttacgtggca agcaaaatta cacatgtcgg tgtgagacta tagttagttg cgacgggtac 900 gtcgttaaaa gaatagctat cagtccaggc ctgtatggga agccttcagg ctatgctgct 960 acgatgcacc gcgagggatt cttgtgctgc aaagtgacag acacattgaa cggggagagg

1020 gtctcttttc ccgtgtgcac gtatgtgcca gctacattgt gtgaccaaat gactggcata

1080 ctggcaacag atgtcagtgc ggacgacgcg caaaaactgc tggttgggct caaccagcgt

1140 atagtcgtca acggtcgcac ccagagaaac accaatacca tgaaaaatta ccttttgccc

1200 gtagtggccc aggcatttgc taggtgggca aaggaatata aggaagatca agaagatgaa

1260 aggccactag gactacgaga tagacagtta gtcatggggt gttgttgggc ttttagaagg

1320 cacaagataa catctattta taagcgcccg gatacccaaa ccatcatcaa agtgaacagc

1380 gatttccact cattcgtgct gcccaggata ggcagtaaca cattggagat cgggctgaga

1440 acaagaatca ggaaaatgtt agaggagcac aaggagccgt cacctctcat taccgccgag

1500 gacgtacaag aagctaagtg cgcagccgat gaggctaagg aggtgcgtga agccgaggag

1560 ttgcgcgcag ctctaccacc tttggcagct gatgttgagg agcccactct ggaagccgat

1620 gtcgacttga tgttacaaga ggctggggcc ggctcagtgg agacacctcg tggcttgata

1680 aaggttacca gctacgctgg cgaggacaag atcggctctt acgctgtgct ttctccgcag

1740 gctgtactca agagtgaaaa attatcttgc atccaccctc tcgctgaaca agtcatagtg

1800 ataacacact ctggccgaaa agggcgttat gccgtggaac cataccatgg taaagtagtg

1860 gtgccagagg gacatgcaat acccgtccag gactttcaag ctctgagtga aagtgccacc

1920 attgtgtaca acgaacgtga gttcgtaaac aggtacctgc accatattgc cacacatgga

1980 ggagcgctga acactgatga agaatattac aaaactgtca agcccagcga gcacgacggc

2040 gaatacctgt acgacatcga caggaaacag tgcgtcaaga aagagctagt cactgggcta

2100 gggctcacag gcgagctggt cgatcctccc ttccatgaat tcgcctacga gagtctgaga

2160 acacgaccag ccgctcctta ccaagtacca accatagggg tgtatggcgt gccaggatca

2220 ggcaagtctg gcatcattaa aagcgcagtc accaaaaaag atctagtggt gagcgccaag

2280 aaagaaaact gtgcagaaat tataagggac gtcaagaaaa tgaaagggct ggacgtcaat

2340 gccagaactg tggactcagt gctcttgaat ggatgcaaac accccgtaga gaccctgtat

2400 attgacgagg cttttgcttg tcatgcaggt actctcagag cgctcatagc cattataaga

2460 cctaaaaagg cagtgctctg cggagatccc aaacagtgcg gtttttttaa catgatgtgc

2520 ctgaaagtgc attttaacca cgagatttgc acacaagtct tccacaaaag catctctcgc

2580 cgttgcacta aatctgtgac ttcggtcgtc tcaaccttgt tttacgacaa aaaaatgaga

2640 acgacgaatc cgaaagagac taagattgtg attgacacta ccggcagtac caaacctaag

2700 caggacgatc tcattctcac ttgtttcaga gggtgggtga agcagttgca aatagattac

2760 aaaggcaacg aaataatgac ggcagctgcc tctcaagggc tgacccgtaa aggtgtgtat

2820 gccgttcggt acaaggtgaa tgaaaatcct ctgtacgcac ccacctcaga acatgtgaac

2880 gtcctactga cccgcacgga ggaccgcatc gtgtggaaaa cactagccgg cgacccatgg

2940 ataaaaacac tgactgccaa gtaccctggg aatttcactg ccacgataga ggagtggcaa

3000 gcagagcatg atgccatcat gaggcacatc ttggagagac cggaccctac cgacgtcttc

3060 cagaataagg caaacgtgtg ttgggccaag gctttagtgc cggtgctgaa gaccgctggc

3120 atagacatga ccactgaaca atggaacact gtggattatt ttgaaacgga caaagctcac

3180 tcagcagaga tagtattgaa ccaactatgc gtgaggttct ttggactcga tctggactcc

3240 ggtctatttt ctgcacccac tgttccgtta tccattagga ataatcactg ggataactcc

3300 ccgtcgccta acatgtacgg gctgaataaa gaagtggtcc gtcagctctc tcgcaggtac

3360 ccacaactgc ctcgggcagt tgccactggt agagtctatg acatgaacac tggtacactg

3420 cgcaattatg atccgcgcat aaacctagta cctgtaaaca gaagactgcc tcatgcttta

3480 gtcctccacc ataatgaaca cccacagagt gacttttctt cattcgtcag caaattgaag

3540 ggcagaactg tcctggtggt cggggaaaag ttgtccgtcc caggcaaaat ggttgactgg

3600 ttgtcagacc ggcctgaggc taccttcaga gctcggctgg atttaggcat cccaggtgat

3660 gtgcccaaat atgacataat atttgttaat gtgaggaccc catataaata ccatcactat

3720 cagcagtgtg aagaccatgc cattaagcta agcatgttga ccaagaaagc atgtctgcat

3780 ctgaatcccg gcggaacctg tgtcagcata ggttatggtt acgctgacag ggccagcgaa

3840 agcatcattg gtgctatagc gcggcagttc aagttttccc gagtatgcaa accgaaatcc

3900 tcacttgagg agacggaagt tctgtttgta ttcattgggt acgatcgcaa ggcccgtacg

3960 cacaatcctt acaagctatc atcaaccttg accaacattt atacaggttc cagactccac

4020 gaagccggat gtgcaccctc atatcatgtg gtgcgagggg atattgccac ggccaccgaa

4080 ggagtgatta taaatgctgc taacagcaaa ggacaacctg gcggaggggt gtgcggagcg

4140 ctgtataaga aattcccgga aagtttcgat ttacagccga tcgaagtagg aaaagcgcga

4200 ctggtcaaag gtgcagctaa acatatcatt catgccgtag gaccaaactt caacaaagtt

4260 tcggaggttg aaggtgacaa acagttggca gaggcttatg agtccatcgc taagattgtc

4320 aacgataaca attacaagtc agtagcgatt ccactgttgt ccaccggcat cttttccggg

4380 aacaaagatc gactaaccca atcattgaac catttgctga cagctttaga caccactgat

4440 gcagatgtag ccatatactg cagggacaag aaatgggaaa tgactctcaa ggaagcagtg

4500 gctaggagag aagcagtgga ggagatatgc atatccgacg attcttcagt gacagaacct

4560 gatgcagagc tggtgagggt gcatcccaag agttctttgg ctggaaggaa gggctacagc

4620 acaagcgatg gcaaaacttt ctcatatttg gaagggacca agtttcacca ggcggccaag

4680 gatatagcag aaattaatgc catgtggccc gttgcaacgg aggccaatga gcaggtatgc

4740 atgtatatcc tcggagaaag catgagcagt attaggtcga aatgccccgt cgaggagtcg

4800 gaagcctcca caccacctag cacgctgcct tgcttgtgca tccatgccat gactccagaa

4860 agagtacagc gcctaaaagc ctcacgtcca gaacaaatta ctgtgtgctc atcctttcca

4920 ttgccgaagt atagaatcac tggtgtgcag aagatccaat gctcccagcc tatattgttc

4980 tcaccgaaag tgcctgcgta tattcatcca aggaagtatc tcgtggaaac accaccggta

5040 gacgagactc cggagccatc ggcagagaac caatccacag aggggacacc tgaacaacca

5100 ccacttataa ccgaggatga gaccaggact agaacgcctg agccgatcat catcgaagaa

5160 gaagaagaag atagcataag tttgctgtca gatggcccga cccaccaggt gctgcaagtc

5220 gaggcagaca ttcacgggcc gccctctgta tctagctcat cctggtccat tcctcatgca

5280 tccgactttg atgtggacag tttatccata cttgacaccc tggagggagc tagcgtgacc

5340 agcggggcaa cgtcagccga gactaactct tacttcgcaa agagtatgga gtttctggcg

5400 cgaccggtgc ctgcgcctcg aacagtattc aggaaccctc cacatcccgc tccgcgcaca

5460 agaacaccgt cacttgcacc cagcagggcc tgctccagaa ccagcctagt ttccaccccg

5520 ccaggcgtga atagggtgat cactagagag gagctcgaag cgcttacccc gtcacgcact

5580 cctagcaggt cggtctccag aaccagcctg gtctccaacc cgccaggcgt aaatagggtg

5640 attacaagag aggagtttga ggcgttcgta gcacaacaac aatgacggtt tgatgcgggt

5700 gcatacatct tttcctccga caccggtcaa gggcatttac aacaaaaatc agtaaggcaa

5760 acggtgctat ccgaagtggt gttggagagg accgaattgg agatttcgta tgccccgcgc

5820 ctcgaccaag aaaaagaaga attactacgc aagaaattac agttaaatcc cacacctgct

5880 aacagaagca gataccagtc caggaaggtg gagaacatga aagccataac agctagacgt

5940 attctgcaag gcctagggca ttatttgaag gcagaaggaa aagtggagtg ctaccgaacc

6000 ctgcatcctg ttcctttgta ttcatctagt gtgaaccgtg ccttttcaag ccccaaggtc

6060 gcagtggaag cctgtaacgc catgttgaaa gagaactttc cgactgtggc ttcttactgt

6120 attattccag agtacgatgc ctatttggac atggttgacg gagcttcatg ctgcttagac

6180 actgccagtt tttgccctgc aaagctgcgc agctttccaa agaaacactc ctatttggaa

6240 cccacaatac gatcggcagt gccttcagcg atccagaaca cgctccagaa cgtcctggca

6300 gctgccacaa aaagaaattg caatgtcacg caaatgagag aattgcccgt attggattcg

6360 gcggccttta atgtggaatg cttcaagaaa tatgcgtgta ataatgaata ttgggaaacg

6420 tttaaagaaa accccatcag gcttactgaa gaaaacgtgg taaattacat taccaaatta

6480 aaaggaccaa aagctgctgc tctttttgcg aagacacata atttgaatat gttgcaggac

6540 ataccaatgg acaggtttgt aatggactta aagagagacg tgaaagtgac tccaggaaca

6600 aaacatactg aagaacggcc caaggtacag gtgatccagg ctgccgatcc gctagcaaca

6660 gcgtatctgt gcggaatcca ccgagagctg gttaggagat taaatgcggt cctgcttccg

6720 aacattcata cactgtttga tatgtcggct gaagactttg acgctattat agccgagcac

6780 ttccagcctg gggattgtgt tctggaaact gacatcgcgt cgtttgataa aagtgaggac

6840 gacgccatgg ctctgaccgc gttaatgatt ctggaagact taggtgtgga cgcagagctg

6900 ttgacgctga ttgaggcggc tttcggcgaa atttcatcaa tacatttgcc cactaaaact

6960 aaatttaaat tcggagccat gatgaaatct ggaatgttcc tcacactgtt tgtgaacaca

7020 gtcattaaca ttgtaatcgc aagcagagtg ttgagagaac ggctaaccgg atcaccatgt

7080 gcagcattca ttggagatga caatatcgtg aaaggagtca aatcggacaa attaatggca

7140 gacaggtgcg ccacctggtt gaatatggaa gtcaagatta tagatgctgt ggtgggcgag

7200 aaagcgcctt atttctgtgg agggtttatt ttgtgtgact ccgtgaccgg cacagcgtgc

7260 cgtgtggcag accccctaaa aaggctgttt aagctaggca aacctctggc agcagacgat

7320 gaacatgatg atgacaggag aagggcattg catgaggagt caacacgctg gaaccgagtg

7380 ggtattcttt cagagctgtg caaggcagta gaatcaaggt atgaaaccgt aggaacttcc

7440 atcatagtta tggccatgac tactctagct agcagtgtta aatcattcag ctacctgaga

7500 ggggccccta taactctcta cggctaacct gaatggacta cgacatagtc tagtccgcca

7560 agactagtat gtttgtgttt cttgtgctgc tgcctcttgt gtcttctcag tgtgtggtga

7620 gatttccaaa tattacaaat ctgtgtccat ttggagaagt gtttaatgca acaagatttg

7680 catctgtgta tgcatggaat agaaaaagaa tttctaattg tgtggctgat tattctgtgc

7740 tgtataatag tgcttctttt tccacattta aatgttatgg agtgtctcca acaaaattaa

7800 atgatttatg ttttacaaat gtgtatgctg attcttttgt gatcagaggt gatgaagtga

7860 gacagattgc ccccggacag acaggaaaaa ttgctgatta caattacaaa ctgcctgatg

7920 attttacagg atgtgtgatt gcttggaatt ctaataattt agattctaaa gtgggaggaa

7980 attacaatta tctgtacaga ctgtttagaa aatcaaatct gaaacctttt gaaagagata

8040 tttcaacaga aatttatcag gctggatcaa caccttgtaa tggagtggaa ggatttaatt

8100 gttattttcc attacagagc tatggatttc agccaaccaa tggtgtggga tatcagccat

8160 atagagtggt ggtgctgtct tttgaactgc tgcatgcacc tgcaacagtg tgtggaccta

8220 aaggctcccc cggctccggc tccggatctg gttatattcc tgaagctcca agagatgggc

8280 aagcttacgt tcgtaaagat ggcgaatggg tattactttc taccttttta ggccggtccc

8340 tggaggtgct gttccagggc cccggctgat gactcgagct ggtactgcat gcacgcaatg

8400 ctagctgccc ctttcccgtc ctgggtaccc cgagtctccc ccgacctcgg gtcccaggta

8460 tgctcccacc tccacctgcc ccactcacca cctctgctag ttccagacac ctcccaagca

8520 cgcagcaatg cagctcaaaa cgcttagcct agccacaccc ccacgggaaa cagcagtgat

8580 taacctttag caataaacga aagtttaact aagctatact aaccccaggg ttggtcaatt

8640 tcgtgccagc cacaccgcgg ccgcatgaat acagcagcaa ttggcaagct gcttacatag

8700 aactcgcggc gattggcatg ccgccttaaa atttttattt tattttttct tttcttttcc

8760 gaatcggatt ttgtttttaa tatttcaaaa aaaaaaaaaa aaaaaaaaaa aaaaaagcat

8820 atgactaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

8880 aaaaaaaaaa aaaaaa

8896

Sequence Number (ID) : 27

Length : 9079

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .9079

> note, RBS004.4

- source, 1 . . 9079

> mol_type, other RNA

> organism, synthetic construct Residues : gatgggcggc gcatgagaga agcccagacc aattacctac ccaaaatgga gaaagttcac 60 gttgacatcg aggaagacag cccattcctc agagctttgc agcggagctt cccgcagttt 120 gaggtagaag ccaagcaggt cactgataat gaccatgcta atgccagagc gttttcgcat 180 ctggcttcaa aactgatcga aacggaggtg gacccatccg acacgatcct tgacattgga 240 agtgcgcccg cccgcagaat gtattctaag cacaagtatc attgtatctg tccgatgaga 300 tgtgcggaag atccggacag attgtataag tatgcaacta agctgaagaa aaactgtaag 360 gaaataactg ataaggaatt ggacaagaaa atgaaggagc tcgccgccgt catgagcgac 420 cctgacctgg aaactgagac tatgtgcctc cacgacgacg agtcgtgtcg ctacgaaggg 480 caagtcgctg tttaccagga tgtatacgcg gttgacggac cgacaagtct ctatcaccaa 540 gccaataagg gagttagagt cgcctactgg ataggctttg acaccacccc ttttatgttt 600 aagaacttgg ctggagcata tccatcatac tctaccaact gggccgacga aaccgtgtta 660 acggctcgta acataggcct atgcagctct gacgttatgg agcggtcacg tagagggatg 720 tccattctta gaaagaagta tttgaaacca tccaacaatg ttctattctc tgttggctcg 780 accatctacc acgaaaagag ggacttactg aggagctggc acctgccgtc tgtatttcac 840 ttacgtggca agcaaaatta cacatgtcgg tgtgagacta tagttagttg cgacgggtac 900 gtcgttaaaa gaatagctat cagtccaggc ctgtatggga agccttcagg ctatgctgct 960 acgatgcacc gcgagggatt cttgtgctgc aaagtgacag acacattgaa cggggagagg

1020 gtctcttttc ccgtgtgcac gtatgtgcca gctacattgt gtgaccaaat gactggcata 1080 ctggcaacag atgtcagtgc ggacgacgcg caaaaactgc tggttgggct caaccagcgt

1140 atagtcgtca acggtcgcac ccagagaaac accaatacca tgaaaaatta ccttttgccc

1200 gtagtggccc aggcatttgc taggtgggca aaggaatata aggaagatca agaagatgaa

1260 aggccactag gactacgaga tagacagtta gtcatggggt gttgttgggc ttttagaagg

1320 cacaagataa catctattta taagcgcccg gatacccaaa ccatcatcaa agtgaacagc

1380 gatttccact cattcgtgct gcccaggata ggcagtaaca cattggagat cgggctgaga

1440 acaagaatca ggaaaatgtt agaggagcac aaggagccgt cacctctcat taccgccgag

1500 gacgtacaag aagctaagtg cgcagccgat gaggctaagg aggtgcgtga agccgaggag

1560 ttgcgcgcag ctctaccacc tttggcagct gatgttgagg agcccactct ggaagccgat

1620 gtcgacttga tgttacaaga ggctggggcc ggctcagtgg agacacctcg tggcttgata

1680 aaggttacca gctacgctgg cgaggacaag atcggctctt acgctgtgct ttctccgcag

1740 gctgtactca agagtgaaaa attatcttgc atccaccctc tcgctgaaca agtcatagtg

1800 ataacacact ctggccgaaa agggcgttat gccgtggaac cataccatgg taaagtagtg

1860 gtgccagagg gacatgcaat acccgtccag gactttcaag ctctgagtga aagtgccacc

1920 attgtgtaca acgaacgtga gttcgtaaac aggtacctgc accatattgc cacacatgga

1980 ggagcgctga acactgatga agaatattac aaaactgtca agcccagcga gcacgacggc

2040 gaatacctgt acgacatcga caggaaacag tgcgtcaaga aagagctagt cactgggcta

2100 gggctcacag gcgagctggt cgatcctccc ttccatgaat tcgcctacga gagtctgaga

2160 acacgaccag ccgctcctta ccaagtacca accatagggg tgtatggcgt gccaggatca

2220 ggcaagtctg gcatcattaa aagcgcagtc accaaaaaag atctagtggt gagcgccaag

2280 aaagaaaact gtgcagaaat tataagggac gtcaagaaaa tgaaagggct ggacgtcaat

2340 gccagaactg tggactcagt gctcttgaat ggatgcaaac accccgtaga gaccctgtat

2400 attgacgagg cttttgcttg tcatgcaggt actctcagag cgctcatagc cattataaga

2460 cctaaaaagg cagtgctctg cggagatccc aaacagtgcg gtttttttaa catgatgtgc

2520 ctgaaagtgc attttaacca cgagatttgc acacaagtct tccacaaaag catctctcgc 2580 cgttgcacta aatctgtgac ttcggtcgtc tcaaccttgt tttacgacaa aaaaatgaga

2640 acgacgaatc cgaaagagac taagattgtg attgacacta ccggcagtac caaacctaag

2700 caggacgatc tcattctcac ttgtttcaga gggtgggtga agcagttgca aatagattac

2760 aaaggcaacg aaataatgac ggcagctgcc tctcaagggc tgacccgtaa aggtgtgtat

2820 gccgttcggt acaaggtgaa tgaaaatcct ctgtacgcac ccacctcaga acatgtgaac

2880 gtcctactga cccgcacgga ggaccgcatc gtgtggaaaa cactagccgg cgacccatgg

2940 ataaaaacac tgactgccaa gtaccctggg aatttcactg ccacgataga ggagtggcaa

3000 gcagagcatg atgccatcat gaggcacatc ttggagagac cggaccctac cgacgtcttc

3060 cagaataagg caaacgtgtg ttgggccaag gctttagtgc cggtgctgaa gaccgctggc

3120 atagacatga ccactgaaca atggaacact gtggattatt ttgaaacgga caaagctcac

3180 tcagcagaga tagtattgaa ccaactatgc gtgaggttct ttggactcga tctggactcc

3240 ggtctatttt ctgcacccac tgttccgtta tccattagga ataatcactg ggataactcc

3300 ccgtcgccta acatgtacgg gctgaataaa gaagtggtcc gtcagctctc tcgcaggtac

3360 ccacaactgc ctcgggcagt tgccactggt agagtctatg acatgaacac tggtacactg

3420 cgcaattatg atccgcgcat aaacctagta cctgtaaaca gaagactgcc tcatgcttta

3480 gtcctccacc ataatgaaca cccacagagt gacttttctt cattcgtcag caaattgaag

3540 ggcagaactg tcctggtggt cggggaaaag ttgtccgtcc caggcaaaat ggttgactgg

3600 ttgtcagacc ggcctgaggc taccttcaga gctcggctgg atttaggcat cccaggtgat

3660 gtgcccaaat atgacataat atttgttaat gtgaggaccc catataaata ccatcactat

3720 cagcagtgtg aagaccatgc cattaagcta agcatgttga ccaagaaagc atgtctgcat

3780 ctgaatcccg gcggaacctg tgtcagcata ggttatggtt acgctgacag ggccagcgaa

3840 agcatcattg gtgctatagc gcggcagttc aagttttccc gagtatgcaa accgaaatcc

3900 tcacttgagg agacggaagt tctgtttgta ttcattgggt acgatcgcaa ggcccgtacg

3960 cacaatcctt acaagctatc atcaaccttg accaacattt atacaggttc cagactccac

4020 gaagccggat gtgcaccctc atatcatgtg gtgcgagggg atattgccac ggccaccgaa 4080 ggagtgatta taaatgctgc taacagcaaa ggacaacctg gcggaggggt gtgcggagcg

4140 ctgtataaga aattcccgga aagtttcgat ttacagccga tcgaagtagg aaaagcgcga

4200 ctggtcaaag gtgcagctaa acatatcatt catgccgtag gaccaaactt caacaaagtt

4260 tcggaggttg aaggtgacaa acagttggca gaggcttatg agtccatcgc taagattgtc

4320 aacgataaca attacaagtc agtagcgatt ccactgttgt ccaccggcat cttttccggg

4380 aacaaagatc gactaaccca atcattgaac catttgctga cagctttaga caccactgat

4440 gcagatgtag ccatatactg cagggacaag aaatgggaaa tgactctcaa ggaagcagtg

4500 gctaggagag aagcagtgga ggagatatgc atatccgacg attcttcagt gacagaacct

4560 gatgcagagc tggtgagggt gcatcccaag agttctttgg ctggaaggaa gggctacagc

4620 acaagcgatg gcaaaacttt ctcatatttg gaagggacca agtttcacca ggcggccaag

4680 gatatagcag aaattaatgc catgtggccc gttgcaacgg aggccaatga gcaggtatgc

4740 atgtatatcc tcggagaaag catgagcagt attaggtcga aatgccccgt cgaggagtcg

4800 gaagcctcca caccacctag cacgctgcct tgcttgtgca tccatgccat gactccagaa

4860 agagtacagc gcctaaaagc ctcacgtcca gaacaaatta ctgtgtgctc atcctttcca

4920 ttgccgaagt atagaatcac tggtgtgcag aagatccaat gctcccagcc tatattgttc

4980 tcaccgaaag tgcctgcgta tattcatcca aggaagtatc tcgtggaaac accaccggta

5040 gacgagactc cggagccatc ggcagagaac caatccacag aggggacacc tgaacaacca

5100 ccacttataa ccgaggatga gaccaggact agaacgcctg agccgatcat catcgaagaa

5160 gaagaagaag atagcataag tttgctgtca gatggcccga cccaccaggt gctgcaagtc

5220 gaggcagaca ttcacgggcc gccctctgta tctagctcat cctggtccat tcctcatgca

5280 tccgactttg atgtggacag tttatccata cttgacaccc tggagggagc tagcgtgacc

5340 agcggggcaa cgtcagccga gactaactct tacttcgcaa agagtatgga gtttctggcg

5400 cgaccggtgc ctgcgcctcg aacagtattc aggaaccctc cacatcccgc tccgcgcaca

5460 agaacaccgt cacttgcacc cagcagggcc tgctccagaa ccagcctagt ttccaccccg

5520 ccaggcgtga atagggtgat cactagagag gagctcgaag cgcttacccc gtcacgcact 5580 cctagcaggt cggtctccag aaccagcctg gtctccaacc cgccaggcgt aaatagggtg

5640 attacaagag aggagtttga ggcgttcgta gcacaacaac aatgacggtt tgatgcgggt

5700 gcatacatct tttcctccga caccggtcaa gggcatttac aacaaaaatc agtaaggcaa

5760 acggtgctat ccgaagtggt gttggagagg accgaattgg agatttcgta tgccccgcgc

5820 ctcgaccaag aaaaagaaga attactacgc aagaaattac agttaaatcc cacacctgct

5880 aacagaagca gataccagtc caggaaggtg gagaacatga aagccataac agctagacgt

5940 attctgcaag gcctagggca ttatttgaag gcagaaggaa aagtggagtg ctaccgaacc

6000 ctgcatcctg ttcctttgta ttcatctagt gtgaaccgtg ccttttcaag ccccaaggtc

6060 gcagtggaag cctgtaacgc catgttgaaa gagaactttc cgactgtggc ttcttactgt

6120 attattccag agtacgatgc ctatttggac atggttgacg gagcttcatg ctgcttagac

6180 actgccagtt tttgccctgc aaagctgcgc agctttccaa agaaacactc ctatttggaa

6240 cccacaatac gatcggcagt gccttcagcg atccagaaca cgctccagaa cgtcctggca

6300 gctgccacaa aaagaaattg caatgtcacg caaatgagag aattgcccgt attggattcg

6360 gcggccttta atgtggaatg cttcaagaaa tatgcgtgta ataatgaata ttgggaaacg

6420 tttaaagaaa accccatcag gcttactgaa gaaaacgtgg taaattacat taccaaatta

6480 aaaggaccaa aagctgctgc tctttttgcg aagacacata atttgaatat gttgcaggac

6540 ataccaatgg acaggtttgt aatggactta aagagagacg tgaaagtgac tccaggaaca

6600 aaacatactg aagaacggcc caaggtacag gtgatccagg ctgccgatcc gctagcaaca

6660 gcgtatctgt gcggaatcca ccgagagctg gttaggagat taaatgcggt cctgcttccg

6720 aacattcata cactgtttga tatgtcggct gaagactttg acgctattat agccgagcac

6780 ttccagcctg gggattgtgt tctggaaact gacatcgcgt cgtttgataa aagtgaggac

6840 gacgccatgg ctctgaccgc gttaatgatt ctggaagact taggtgtgga cgcagagctg

6900 ttgacgctga ttgaggcggc tttcggcgaa atttcatcaa tacatttgcc cactaaaact

6960 aaatttaaat tcggagccat gatgaaatct ggaatgttcc tcacactgtt tgtgaacaca

7020 gtcattaaca ttgtaatcgc aagcagagtg ttgagagaac ggctaaccgg atcaccatgt 7080 gcagcattca ttggagatga caatatcgtg aaaggagtca aatcggacaa attaatggca

7140 gacaggtgcg ccacctggtt gaatatggaa gtcaagatta tagatgctgt ggtgggcgag

7200 aaagcgcctt atttctgtgg agggtttatt ttgtgtgact ccgtgaccgg cacagcgtgc

7260 cgtgtggcag accccctaaa aaggctgttt aagctaggca aacctctggc agcagacgat

7320 gaacatgatg atgacaggag aagggcattg catgaggagt caacacgctg gaaccgagtg

7380 ggtattcttt cagagctgtg caaggcagta gaatcaaggt atgaaaccgt aggaacttcc

7440 atcatagtta tggccatgac tactctagct agcagtgtta aatcattcag ctacctgaga

7500 ggggccccta taactctcta cggctaacct gaatggacta cgacatagtc tagtccgcca

7560 agactagtat gtttgtgttt cttgtgctgc tgcctcttgt gtcttctcag tgtgtggtga

7620 gatttccaaa tattacaaat ctgtgtccat ttggagaagt gtttaatgca acaagatttg

7680 catctgtgta tgcatggaat agaaaaagaa tttctaattg tgtggctgat tattctgtgc

7740 tgtataatag tgcttctttt tccacattta aatgttatgg agtgtctcca acaaaattaa

7800 atgatttatg ttttacaaat gtgtatgctg attcttttgt gatcagaggt gatgaagtga

7860 gacagattgc ccccggacag acaggaaaaa ttgctgatta caattacaaa ctgcctgatg

7920 attttacagg atgtgtgatt gcttggaatt ctaataattt agattctaaa gtgggaggaa

7980 attacaatta tctgtacaga ctgtttagaa aatcaaatct gaaacctttt gaaagagata

8040 tttcaacaga aatttatcag gctggatcaa caccttgtaa tggagtggaa ggatttaatt

8100 gttattttcc attacagagc tatggatttc agccaaccaa tggtgtggga tatcagccat

8160 atagagtggt ggtgctgtct tttgaactgc tgcatgcacc tgcaacagtg tgtggaccta

8220 aaggctcccc cggctccggc tccggatctg gttatattcc tgaagctcca agagatgggc

8280 aagcttacgt tcgtaaagat ggcgaatggg tattactttc taccttttta ggaagcggca

8340 gcggatctga acagtacatt aaatggcctt ggtacatttg gcttggattt attgcaggat

8400 taattgcaat tgtgatggtg acaattatgt tatgttgtat gacatcatgt tgttcttgtt

8460 taaaaggatg ttgttcttgt ggaagctgtt gtaaatttga tgaagatgat tctgaacctg

8520 tgttaaaagg agtgaaattg cattacacat gatgactcga gctggtactg catgcacgca 8580 atgctagctg cccctttccc gtcctgggta ccccgagtct cccccgacct cgggtcccag

8640 gtatgctccc acctccacct gccccactca ccacctctgc tagttccaga cacctcccaa

8700 gcacgcagca atgcagctca aaacgcttag cctagccaca cccccacggg aaacagcagt

8760 gattaacctt tagcaataaa cgaaagttta actaagctat actaacccca gggttggtca

8820 atttcgtgcc agccacaccg cggccgcatg aatacagcag caattggcaa gctgcttaca

8880 tagaactcgc ggcgattggc atgccgcctt aaaattttta ttttattttt tcttttcttt

8940 tccgaatcgg attttgtttt taatatttca aaaaaaaaaa aaaaaaaaaa aaaaaaaaag

9000 catatgacta aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

9060 aaaaaaaaaa aaaaaaaaa

9079

Sequence Number (ID) : 28

Length : 327

Molecule Type : AA

Features Location/Qualifiers :

- REGION j 1. . 327

> note, Vaccine Antigen

- source, 1 . . 327

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCWRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN 60

SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT 120

GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVEGFNCYF 180

PLQSYGFQPT NGVGYQPYRV VVLSF ELLHA PATVCGPKGS PGSGSGSGYI PEAPRDGQAY 240

VRKDGEWVLL STFLGSGSGS EQYIKWPWYI WLGFIAGLIA IVMVTIMLCC MTSCCSCLKG 300

CCSCGSCCKF DEDDSEPVLK GVKLHYT 327

Sequence Number ( ID) : 29

Length : 311

Molecule Type : AA

Features Location/Qualifiers :

- REGION, 1. . 311

> note, BNT162b3c

- source, 1. . 311

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLTV RFPNITNLCP FGEVFNATRF ASVYAWNRKR ISNCVADYSV 60

LYNSASFSTF KCYGVSPTKL NDLCFTNVYA DSFVIRGDEV RQIAPGQTGK IADYNYKLPD 120

DFTGCVIAWN SNNLDSKVGG NYNYLYRLFR KSNLKPFERD ISTEIYQAGS TPCNGVEGFN 180 CYFPLQSYGF QPTNGVGYQP YRWVLSFEL LHAPATVCGP KGSPGSGSGS GYIPEAPRDG 240 QAYVRKDGEW VLLSTFLGSG SGSEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC 300 LKGCCSCGSC C 311

Sequence Number (ID) : 30

Length : 1397

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .1397

> note, BNT162b3c

- source, 1 . .1397

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgtttg 60 tgtttcttgt gctgctgcct cttgtgtctt ctcagtgtgt gaatttgaca gtgagatttc 120 caaatattac aaatctgtgt ccatttggag aagtgtttaa tgcaacaaga tttgcatctg 180 tgtatgcatg gaatagaaaa agaatttcta attgtgtggc tgattattct gtgctgtata 240 atagtgcttc tttttccaca tttaaatgtt atggagtgtc tccaacaaaa ttaaatgatt 300 tatgttttac aaatgtgtat gctgattctt ttgtgatcag aggtgatgaa gtgagacaga 360 ttgcccccgg acagacagga aaaattgctg attacaatta caaactgcct gatgatttta 420 caggatgtgt gattgcttgg aattctaata atttagattc taaagtggga ggaaattaca 480 attatctgta cagactgttt agaaaatcaa atctgaaacc ttttgaaaga gatatttcaa 540 cagaaattta tcaggctgga tcaacacctt gtaatggagt ggaaggattt aattgttatt 600 ttccattaca gagctatgga tttcagccaa ccaatggtgt gggatatcag ccatatagag 660 tggtggtgct gtcttttgaa ctgctgcatg cacctgcaac agtgtgtgga cctaaaggct 720 cccccggctc cggctccgga tctggttata ttcctgaagc tccaagagat gggcaagctt 780 acgttcgtaa agatggcgaa tgggtattac tttctacctt tttaggaagc ggcagcggat 840 ctgaacagta cattaaatgg ccttggtaca tttggcttgg atttattgca ggattaattg 900 caattgtgat ggtgacaatt atgttatgtt gtatgacatc atgttgttct tgtttaaaag 960 gatgttgttc ttgtggaagc tgttgttgat gactcgagct ggtactgcat gcacgcaatg

1020 ctagctgccc ctttcccgtc ctgggtaccc cgagtctccc ccgacctcgg gtcccaggta

1080 tgctcccacc tccacctgcc ccactcacca cctctgctag ttccagacac ctcccaagca

1140 cgcagcaatg cagctcaaaa cgcttagcct agccacaccc ccacgggaaa cagcagtgat

1200 taacctttag caataaacga aagtttaact aagctatact aaccccaggg ttggtcaatt

1260 tcgtgccagc cacaccctgg agctagcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaagca

1320 tatgactaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

1380 aaaaaaaaaa aaaaaaa

1397

Sequence Number (ID) : 31 Length : 314

Molecule Type : AA Features Location/Qualifiers :

- REGION j 1. .314

> note, BNT162b3d

- source, 1 . . 314

> mol type, protein

> organism, synthetic construct

Residues :

MDWIWRILFL VGAATGAHSQ MQVRFPNITN LCPFGEVFNA TRFASVYAWN RKRISNCVAD 60

YSVLYNSASF STFKCYGVSP TKLNDLCFTN VYADSFVIRG DEVRQIAPGQ TGKIADYNYK 120

LPDDFTGCVI AWNSNNLDSK VGGNYNYLYR LFRKSNLKPF ERDISTEIYQ AGSTPCNGVE 180

GFNCYFPLQS YGFQPTNGVG YQPYRVWLS FELLHAPATV CGPKGSPGSG SGSGYIPEAP 240

RDGQAYVRKD GEIAIVLLSTF L GSGSGSEQYI KWPWYIWLGF IAGLIAIVMV TIMLCCMTSC 300

CSCLKGCCSC GSCC 314

Sequence Number (ID) : 32

Length : 1406

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .1406

> note, BNT162b3d source, 1 . . 1406

> mol_type, other RNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatggatt 60 ggatttggag aatcctgttc ctcgtgggag ccgctacagg agcccactcc cagatgcagg 120 tgagatttcc aaatattaca aatctgtgtc catttggaga agtgtttaat gcaacaagat 180 ttgcatctgt gtatgcatgg aatagaaaaa gaatttctaa ttgtgtggct gattattctg 240 tgctgtataa tagtgcttct ttttccacat ttaaatgtta tggagtgtct ccaacaaaat 300 taaatgattt atgttttaca aatgtgtatg ctgattcttt tgtgatcaga ggtgatgaag 360 tgagacagat tgcccccgga cagacaggaa aaattgctga ttacaattac aaactgcctg 420 atgattttac aggatgtgtg attgcttgga attctaataa tttagattct aaagtgggag 480 gaaattacaa ttatctgtac agactgttta gaaaatcaaa tctgaaacct tttgaaagag 540 atatttcaac agaaatttat caggctggat caacaccttg taatggagtg gaaggattta 600 attgttattt tccattacag agctatggat ttcagccaac caatggtgtg ggatatcagc 660 catatagagt ggtggtgctg tcttttgaac tgctgcatgc acctgcaaca gtgtgtggac 720 ctaaaggctc ccccggctcc ggctccggat ctggttatat tcctgaagct ccaagagatg 780 ggcaagctta cgttcgtaaa gatggcgaat gggtattact ttctaccttt ttaggaagcg 840 gcagcggatc tgaacagtac attaaatggc cttggtacat ttggcttgga tttattgcag 900 gattaattgc aattgtgatg gtgacaatta tgttatgttg tatgacatca tgttgttctt 960 gtttaaaagg atgttgttct tgtggaagct gttgttgatg actcgagctg gtactgcatg

1020 cacgcaatgc tagctgcccc tttcccgtcc tgggtacccc gagtctcccc cgacctcggg

1080 tcccaggtat gctcccacct ccacctgccc cactcaccac ctctgctagt tccagacacc

1140 tcccaagcac gcagcaatgc agctcaaaac gcttagccta gccacacccc cacgggaaac

1200 agcagtgatt aacctttagc aataaacgaa agtttaacta agctatacta accccagggt

1260 tggtcaattt cgtgccagcc acaccctgga gctagcaaaa aaaaaaaaaa aaaaaaaaaa

1320 aaaaaagcat atgactaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

1380 aaaaaaaaaa aaaaaaaaaa aaaaaa

1406

Sequence Number (ID): 33

Length: 9

Molecule Type: AA

Features Location/Qualifiers :

- REGION, 1..9

> note, Linker

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

GSPGSGSGS 9

Sequence Number (ID): 34

Length: 6

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..6

> note, Linker

- source, 1..6

> mol_type, protein

> organism, synthetic construct

Residues : GSGSGS 6

Sequence Number (ID): 35

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

YLQPRTFLL 9

Sequence Number (ID): 36

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9 > mol_type, protein

> organism, synthetic construct Residues :

RLQSLQTYV

Sequence Number (ID): 37

Length: 9

Molecule Type: AA

Features Location/Qualifiers :

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

QYIKWPWYI 9

Sequence Number (ID): 38

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

NYNYLYRLF 9

Sequence Number (ID): 39

Length: 10

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..10

> note, Epitope

- source, 1..10

> mol_type, protein

> organism, synthetic construct Residues :

KWPWYIWLGF 10

Sequence Number (ID): 40

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

QPTESIVRF 9

Sequence Number (ID): 41

Length: 9

Molecule Type: AA

Features Location/Qualifiers :

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

IPFAMQMAY 9

Sequence Number (ID): 42

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

LPFNDGVYF 9

Sequence Number (ID): 43

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol type, protein

> organism, synthetic construct Residues :

GVYFASTEK 9

Sequence Number (ID): 44

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

CVADYSVLY 9 Sequence Number (ID): 45

Length: 9

Molecule Type: AA

Features Location/Qualifiers :

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

KCYGVSPTK 9

Sequence Number (ID): 46

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

FQPTNGVGY 9

Sequence Number (ID): 47

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

GTHWFVTQR 9

Sequence Number (ID): 48

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- REGION, 1..9

> note, Epitope

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

VYDPLQPEL 9

Sequence Number (ID): 49 Length: 1270

Molecule Type: AA

Features Location/Qualifiers :

- REGION, 1..1270

> note, Vaccine sequence

- source, 1. .1270

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS 60

NVTWFHVISG TNGTKRFDNP VLPFNDGVYF ASIEKSNIIR GWIFGTTLDS KTQSLLIVNN 120

ATNWIKVCE FQFCNDPFLD HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN 180

FKNLREFVFK NIDGYFKIYS KHTPIIVREP EDLPQGFSAL EPLVDLPIGI NITRFQTLLA 240

LHRSYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL 300

KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFDEVFN ATRFASVYAW NRKRISNCVA 360

DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYNY 420

KLPDDFTGCV IAWNSNKLDS KVSGNYNYLY RLFRKSNLKP FERDISTEIY QAGNKPCNGV 480

AGFNCYFPLR SYSFRPTYGV GHQPYRWVL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF 540

NGLKGTGVLT ESNKKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN 600

TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EYVNNSYECD 660

IPIGAGICAS YQTQTKSHRR ARSVASQSII AYTMSLGAEN SVAYSNNSIA IPTNFTISVT 720

TEILPVSMTK TSVDCTMYIC GDSTECSNLL LQYGSFCTQL KRALTGIAVE QDKNTQEVFA 780

QVKQIYKTPP IKYFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD 840

IAARDLICAQ KFKGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA 900

YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDWN HNAQALNTLV 960

KQLSSKFGAI SSVLNDIFSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN

1020

LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGWFL HVTYVPAQEK NFTTAPAICH

1080

DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDWIGIV NNTVYDPLQP

1140

ELDSFKEELD KYFKNHTSPD VDLGDISGIN ASWNIQKEI DRLNEVAKNL NESLIDLQEL

1200

GKYEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC LKGCCSCGSC CKFDEDDSEP

1260

VLKGVKLHYT

1270

Sequence Number (ID): 50

Length: 3816

Molecule Type: RNA

Features Location/Qualifiers:

- misc_feature, 1..3816

> note, Coding sequence

- source, 1. .3816

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgt gatctccggc accaatggca ccaagagatt cgacaacccc 240 gtgctgccct tcaacgacgg ggtgtacttt gccagcatcg agaagtccaa catcatcaga 300 ggctggatct tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac 360 gccaccaacg tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcatcgt gagagagccc gaggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcgacga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa cctggccccc ttcttcacct tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggagatgaag tgcggcagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc

1320 aaagtcagcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg

1440 gccggcttca actgctactt cccactgcgg tcctacagct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga agggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaagg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cttcagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 51

Length : 4274

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .4274

> note, Vaccine RNA

- source, 1. .4274

> mol_type, other RNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgacc accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgtgatctcc ggcaccaatg gcaccaagag attcgacaac cccgtgctgc 300 ccttcaacga cggggtgtac tttgccagca tcgagaagtc caacatcatc agaggctgga 360 tcttcggcac cacactggac agcaagaccc agagcctgct gatcgtgaac aacgccacca 420 acgtggtcat caaagtgtgc gagttccagt tctgcaacga ccccttcctg gaccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcat cgtgagagag cccgaggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcga cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacctggcc cccttcttca ccttcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggagatg

1260 aagtgcggca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caagctggac tccaaagtca 1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggccggct

1500 tcaactgcta cttcccactg cggtcctaca gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaagggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta agggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg 2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcttcagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa

4274 Sequence Number (ID): 52 Length: 1270 Molecule Type: AA Features Location/Qualifiers:

- REGION j 1..1270

> note, Vaccine sequence

- source, 1..1270

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS 60

NVTWFHVISG TNGTKRFDNP VLPFNDGVYF ASIEKSNIIR GWIFGTTLDS KTQSLLIVNN 120

ATNWIKVCE FQFCNDPFLD HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN 180

FKNLREFVFK NIDGYFKIYS KHTPIIVREP EDLPQGFSAL EPLVDLPIGI NITRFQTLLA 240

LHRSYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL 300

KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFDEVFN ATRFASVYAW NRKRISNCVA 360

DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGKIADYNY 420

KLPDDFTGCV IAWNSNNLDS KVGGNYNYLY RLFRKSNLKP FERDISTEIY QAGNKPCNGV 480

AGFNCYFPLR SYSFRPTYGV GHQPYRVWL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF 540

NGLKGTGVLT ESNKKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN 600

TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EYVNNSYECD 660

IPIGAGICAS YQTQTKSHRR ARSVASQSII AYTMSLGAEN SVAYSNNSIA IPTNFTISVT 720

TEILPVSMTK TSVDCTMYIC GDSTECSNLL LQYGSFCTQL KRALTGIAVE QDKNTQEVFA 780

QVKQIYKTPP IKYFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD 840

IAARDLICAQ KFKGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA 900

YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDWN HNAQALNTLV 960

KQLSSKFGAI SSVLNDIFSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN

1020

LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGWFL HVTYVPAQEK NFTTAPAICH

1080

DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDWIGIV NNTVYDPLQP

1140

ELDSFKEELD KYFKNHTSPD VDLGDISGIN ASWNIQKEI DRLNEVAKNL NESLIDLQEL

1200

GKYEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC LKGCCSCGSC CKFDEDDSEP

1260

VLKGVKLHYT

1270

Sequence Number (ID): 53

Length: 3816

Molecule Type: RNA

Features Location/Qualifiers:

- misc_feature, 1..3816

> note, Coding sequence

- source, 1. .3816

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgt gatctccggc accaatggca ccaagagatt cgacaacccc 240 gtgctgccct tcaacgacgg ggtgtacttt gccagcatcg agaagtccaa catcatcaga 300 ggctggatct tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac 360 gccaccaacg tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcatcgt gagagagccc gaggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcgacga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa cctggccccc ttcttcacct tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggagatgaag tgcggcagat tgcccctgga cagacaggca agatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa cctggactcc

1320 aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg

1440 gccggcttca actgctactt cccactgcgg tcctacagct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga agggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga 2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaagg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cttcagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc 3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 54

Length : 4274

Molecule Type : RNA

Features Location/Qualifiers :

- misc_feature, 1. .4274

> note, Vaccine RNA

- source, 1 . .4274

> mol type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgacc accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgtgatctcc ggcaccaatg gcaccaagag attcgacaac cccgtgctgc 300 ccttcaacga cggggtgtac tttgccagca tcgagaagtc caacatcatc agaggctgga 360 tcttcggcac cacactggac agcaagaccc agagcctgct gatcgtgaac aacgccacca 420 acgtggtcat caaagtgtgc gagttccagt tctgcaacga ccccttcctg gaccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcat cgtgagagag cccgaggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcga cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacctggcc cccttcttca ccttcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggagatg

1260 aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac tccaaagtcg

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggccggct

1500 tcaactgcta cttcccactg cggtcctaca gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaagggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta agggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcttcagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa

4274 Sequence Number (ID): 55

Length: 1270

Molecule Type: AA

Features Location/Qualifiers :

- source, 1. .1270

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNFTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS 60

NVTWFHAIHV SGTNGTKRFA NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV 120

NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE 180

GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NLVRGLPQGF SALEPLVDLP IGINITRFQT 240

LHISYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL 300

KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFGEVFN ATRFASVYAW NRKRISNCVA 360

DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYNY 420

KLPDDFTGCV IAWNSNNLDS KVGGNYNYLY RLFRKSNLKP FERDISTEIY QAGSTPCNGV 480

KGFNCYFPLQ SYGFQPTYGV GYQPYRWVL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF 540

NGLTGTGVLT ESNKKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN 600

TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EHVNNSYECD 660

IPIGAGICAS YQTQTNSPRR ARSVASQSII AYTMSLGVEN SVAYSNNSIA IPTNFTISVT 720

TEILPVSMTK TSVDCTMYIC GDSTECSNLL LQYGSFCTQL NRALTGIAVE QDKNTQEVFA 780

QVKQIYKTPP IKDFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD 840

IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA 900

YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDWN QNAQALNTLV 960

KQLSSNFGAI SSVLNDILSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN

1020

LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGWFL HVTYVPAQEK NFTTAPAICH

1080

DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNTVYDPLQP

1140

ELDSFKEELD KYFKNHTSPD VDLGDISGIN ASWNIQKEI DRLNEVAKNL NESLIDLQEL

1200

GKYEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC LKGCCSCGSC CKFDEDDSEP

1260

VLKGVKLHYT

1270

Sequence Number (ID): 56

Length: 3817

Molecule Type: RNA

Features Location/Qualifiers:

- source, 1. .3817

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cttcaccacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgcc 240 aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300 atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360 aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420 ctgggcgtct actaccacaa gaacaacaag agctggatgg aaagcgagtt ccgggtgtac 480 agcagcgcca acaactgcac cttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggcaagcagg gcaacttcaa gaacctgcgc gagttcgtgt ttaagaacat cgacggctac 600 ttcaagatct acagcaagca cacccctatc aacctcgtgc ggggcctgcc tcagggcttc 660 tctgctctgg aacccctggt ggatctgccc atcggcatca acatcacccg gtttcagaca 720 ctgcacatca gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcggcga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa ctccgccagc ttcagcacct tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggagatgaag tgcggcagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa cctggactcc

1320 aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca gcaccccttg taacggcgtg

1440 aagggcttca actgctactt cccactgcag tcctacggct ttcagcccac atacggcgtg

1500 ggctatcagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagcacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaacag ccctcggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgtcgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aatagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaaggact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cagaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaactt cggcgccatc agctctgtgc tgaacgatat cctgagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatgac

3817

Sequence Number (ID) : 57

Length : 4274

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1. .4274

> mol_type, other RNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacttcacc accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgccatccac gtgtccggca ccaatggcac caagagattc gccaaccccg 300 tgctgccctt caacgacggg gtgtactttg ccagcaccga gaagtccaac atcatcagag 360 gctggatctt cggcaccaca ctggacagca agacccagag cctgctgatc gtgaacaacg 420 ccaccaacgt ggtcatcaaa gtgtgcgagt tccagttctg caacgacccc ttcctgggcg 480 tctactacca caagaacaac aagagctgga tggaaagcga gttccgggtg tacagcagcg 540 ccaacaactg caccttcgag tacgtgtccc agcctttcct gatggacctg gaaggcaagc 600 agggcaactt caagaacctg cgcgagttcg tgtttaagaa catcgacggc tacttcaaga 660 tctacagcaa gcacacccct atcaacctcg tgcggggcct gcctcagggc ttctctgctc 720 tggaacccct ggtggatctg cccatcggca tcaacatcac ccggtttcag acactgcaca 780 tcagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggagatg

1260 aagtgcggca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac tccaaagtcg

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcagcacccc ttgtaacggc gtgaagggct 1500 tcaactgcta cttcccactg cagtcctacg gctttcagcc cacatacggc gtgggctatc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa cagccctcgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgtcgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaatagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccagaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa cttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc 3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa

4274

Sequence Number (ID) : 58

Length : 1270

Molecule Type : AA

Features Location/Qualif iers : - source, 1 . . 1270

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLF LPF FS 60

NVTWFHAISG TNGTKRFDNP VLPFNDGVYF ASTEKSNIIR GWI FGTTLDS KTQSLLIVNN 120

ATNWIKVCE FQFCNDPFLG VYHKNNKSWM ES E FRVYSSA NNCTFEYVSQ PF LMDLEGKQ 180

GNFKNLRE FV FKNIDGYFKI YSKHTPINLV RDLPQGFSAL EPLVDLPIGI NITRFQTLLA 240

LHRSYLTPGD SSSGWTAGAA AYYVGYLQPR TF LLKYNENG TITDAVDCAL DPLSETKCTL 300

KS FTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFGEVFN ATRFASVYAW NRKRISNCVA 360

DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVI R GDEVRQIAPG QTGKIADYNY 420

KLPDDFTGCV IAIAINSNN LDS KVGGNYNYLY RL FRKSNLKP F E RDISTEIY QAGSTPCNGV 480

EGFNCYFPLQ SYGFQPTYGV GYQPYRVWL SF E LLHAPAT VCGPKKSTNL VKNKCVNFNF 540

NGLTGTGVLT ESNKKF LPFQ QFGRDIDDTT DAVRDPQTL E I LDITPCSFG GVSVITPGTN 600

TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EHVNNSYECD 660

IPIGAGICAS YQTQTNSHRR ARSVASQSII AYTMS LGAEN SVAYSNNSIA IPINFTISVT 720

TE I LPVSMTK TSVDCTMYIC GDSTECSNLL LQYGS FCTQL NRALTGIAVE QDKNTQEVFA 780

QVKQIYKTPP IKDFGGFNFS QI LPDPSKPS KRSFI EDLL F NKVTLADAGF IKQYGDCLGD 840

IAARDLICAQ KFNGLTVLPP L LTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA 900

YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDWN QNAQALNTLV 960

KQLSSNFGAI SSVLNDI LAR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEI RASAN

1020

LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGWF L HVTYVPAQEK NFTTAPAICH

1080

DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ I ITTHNTFVS GNCDVVIGIV NNTVYDPLQP

1140

E LDSFKEE LD KYFKNHTSPD VDLGDISGIN ASWNIQKE I DRLNEVAKNL NESLIDLQE L

1200

GKYEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC LKGCCSCGSC CKFDEDDS EP

1260

VLKGVKLHYT

1270

Sequence Number ( ID) : 59

Length : 3816

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1 . . 3816

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60 agaacacagc tgcctccagc ctacaccaac agctttac ca gaggcgtgta ctac cccgac 120 aaggtgttca gatc cagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgac ct ggttccacgc catctccggc accaatggca ccaagagatt cgacaac ccc 240 gtgctgccct tcaacgacgg ggtgtacttt gccagcaccg agaagtc caa catcatcaga 300 ggctggatct tcggcac cac actggacagc aagacccaga gcctgctgat cgtgaacaac 360 gccaccaacg tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttc ctgggc 420 gtctaccaca agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcc cag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acacccctat caacctcgtg cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcggcga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa ctccgccagc ttcagcacct tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggagatgaag tgcggcagat tgcccctgga cagacaggca agatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa cctggactcc

1320 aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca gcaccccttg taacggcgtg

1440 gaaggcttca actgctactt cccactgcag tcctacggct ttcagcccac atacggcgtg

1500 ggctatcagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcga cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagcacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaacag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccatca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg 2280 aatagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaaggact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cagaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaactt cggcgccatc agctctgtgc tgaacgatat cctggccaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca cccacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc 3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 60

Length : 4274

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1. .4274

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgacc accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgccatctcc ggcaccaatg gcaccaagag attcgacaac cccgtgctgc 300 ccttcaacga cggggtgtac tttgccagca ccgagaagtc caacatcatc agaggctgga 360 tcttcggcac cacactggac agcaagaccc agagcctgct gatcgtgaac aacgccacca 420 acgtggtcat caaagtgtgc gagttccagt tctgcaacga ccccttcctg ggcgtctacc 480 acaagaacaa caagagctgg atggaaagcg agttccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggagatg

1260 aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac tccaaagtcg

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcagcacccc ttgtaacggc gtggaaggct

1500 tcaactgcta cttcccactg cagtcctacg gctttcagcc cacatacggc gtgggctatc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgacgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa cagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca tcaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaatagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccagaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa cttcggcgcc atcagctctg tgctgaacga tatcctggcc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccacccacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgag atctgctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa

4274

Sequence Number (ID) : 61

Length : 1271

Molecule Type : AA

Features Location/Qualif iers :

- source, 1. .1271

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLRT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS 60 NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV 120

NNATNVVIKV CEFQFCNDPF LDVYYHKNNK SWMESGVYSS ANNCTF EYVS QPFLMDLEGK 180

QGNFKNLREF VFKNIDGYFK IYSKHTPINL VRDLPQGFSA LEPLVDLPIG INITRFQTLL 240

ALHRSYLTPG DSSSGWTAGA AAYYVGYLQP RTFLLKYNEN GTITDAVDCA LDPLSETKCT 300

LKSFTVEKGI YQTSNFRVQP TESIVRFPNI TNLCPFGEVF NATRFASVYA WNRKRISNCV 360

ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGKIADYN 420

YKLPDDFTGC VIAWNSNNLD SKVGGNYNYR YRLFRKSNLK PFERDISTEI YQAGSKPCNG 480

VEGFNCYFPL QSYGFQPTNG VGYQPYRWV LSFELLHAPA TVCGPKKSTN LVKNKCVNFN 540

FNGLTGTGVL TESNKKFLPF QQFGRDIADT TDAVRDPQTL EILDITPCSF GGVSVITPGT 600

NTSNQVAVLY QGVNCTEVPV AIHADQLTPT WRVYSTGSNV FQTRAGCLIG AEHVNNSYEC 660

DIPIGAGICA SYQTQTNSRR RARSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTISV 720

TTEILPVSMT KTSVDCTMYI CGDSTECSNL LLQYGSFCTQ LNRALTGIAV EQDKNTQEVF 780

AQVKQIYKTP PIKDFGGFNF SQILPDPSKP SKRSFIEDLL FNKVTLADAG FIKQYGDCLG 840

DIAARDLICA QKFNGLTVLP PLLTDEMIAQ YTSALLAGTI TSGWTFGAGA ALQIPFAMQM 900

AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTA SALGKLQNW NQNAQALNTL 960

VKQLSSNFGA ISSVLNDILS RLDPPEAEVQ IDRLITGRLQ SLQTYVTQQL IRAAEIRASA

1020

NLAATKMSEC VLGQSKRVDF CGKGYHLMSF PQSAPHGVVF LHVTYVPAQE KNFTTAPAIC

1080

HDGKAHFPRE GVFVSNGTHW FVTQRNFYEP QIITTDNTFV SGNCDWIGI VNNTVYDPLQ

1140

PELDSFKE EL DKYFKNHTSP DVDLGDISGI NASWNIQKE IDRLNEVAKN LNESLIDLQE

1200

LGKYEQYIKW PWYIWLGFIA GLIAIVMVTI MLCCMTSCCS CLKGCCSCGS CCKFDEDDSE

1260 PVLKGVKLHY T 1271

Sequence Number ( ID) : 62

Length : 3819

Molecule Type : DNA

Features Location/Qualif iers :

- source, 1 . . 3819

> mol_type, other DNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgagaacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240 aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300 atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360 aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420 ctggacgtct actaccacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480 gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540 cagggcaact tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag 600 atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660 ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780 gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840 ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900 ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960 accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc

1020 aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg

1080 gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg

1140 tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc

1200 cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac

1260 tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac

1320 tccaaagtcg gcggcaacta caattacagg taccggctgt tccggaagtc caatctgaag

1380 cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgtaacggc

1440 gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc

1500 gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc

1560 acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac

1620 ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc

1680 cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg

1740 gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc

1800 aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg

1860 gccattcacg ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg

1920 tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc

1980 gacatcccca tcggcgctgg aatctgcgcc agctaccaga cacagacaaa cagcaggcgg

2040 agagccagaa gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag

2100 aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg

2160 accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc

2220 tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag

2280 ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc

2340 gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc

2400 agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg

2460 ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc

2520 gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct

2580 cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc

2640 acaagcggct ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg

2700 gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg

2760 atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca

2820 agcgccctgg gaaagctgca gaacgtggtc aaccagaatg cccaggcact gaacaccctg

2880 gtcaagcagc tgtcctccaa cttcggcgcc atcagctctg tgctgaacga tatcctgagc

2940 agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag

3000 agcctccaga catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc

3060 aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt

3120 tgcggcaagg gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt

3180 ctgcacgtga catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc

3240 cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg

3300 ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg

3360 tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag

3420 cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc

3480 gacgtggacc tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag

3540 atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa

3600 ctggggaagt acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc

3660 ggactgattg ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc

3720 tgcctgaagg gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag

3780 cccgtgctga agggcgtgaa actgcactac acatgatga

3819

Sequence Number (ID) : 63 Length : 4277

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . .4277

> mol_type, other DNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgaga accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgccatccac gtgtccggca ccaatggcac caagagattc gacaaccccg 300 tgctgccctt caacgacggg gtgtactttg ccagcaccga gaagtccaac atcatcagag 360 gctggatctt cggcaccaca ctggacagca agacccagag cctgctgatc gtgaacaacg 420 ccaccaacgt ggtcatcaaa gtgtgcgagt tccagttctg caacgacccc ttcctggacg 480 tctactacca caagaacaac aagagctgga tggaaagcgg cgtgtacagc agcgccaaca 540 actgcacctt cgagtacgtg tcccagcctt tcctgatgga cctggaaggc aagcagggca 600 acttcaagaa cctgcgcgag ttcgtgttta agaacatcga cggctacttc aagatctaca 660 gcaagcacac ccctatcaac ctcgtgcggg atctgcctca gggcttctct gctctggaac 720 ccctggtgga tctgcccatc ggcatcaaca tcacccggtt tcagacactg ctggccctgc 780 acagaagcta cctgacacct ggcgatagca gcagcggatg gacagctggt gccgccgctt 840 actatgtggg ctacctgcag cctagaacct tcctgctgaa gtacaacgag aacggcacca 900 tcaccgacgc cgtggattgt gctctggatc ctctgagcga gacaaagtgc accctgaagt 960 ccttcaccgt ggaaaagggc atctaccaga ccagcaactt ccgggtgcag cccaccgaat

1020 ccatcgtgcg gttccccaat atcaccaatc tgtgcccctt cggcgaggtg ttcaatgcca

1080 ccagattcgc ctctgtgtac gcctggaacc ggaagcggat cagcaattgc gtggccgact

1140 actccgtgct gtacaactcc gccagcttca gcaccttcaa gtgctacggc gtgtccccta

1200 ccaagctgaa cgacctgtgc ttcacaaacg tgtacgccga cagcttcgtg atccggggag

1260 atgaagtgcg gcagattgcc cctggacaga caggcaagat cgccgactac aactacaagc

1320 tgcccgacga cttcaccggc tgtgtgattg cctggaacag caacaacctg gactccaaag

1380 tcggcggcaa ctacaattac aggtaccggc tgttccggaa gtccaatctg aagcccttcg

1440 agcgggacat ctccaccgag atctatcagg ccggcagcaa gccttgtaac ggcgtggaag

1500 gcttcaactg ctacttccca ctgcagtcct acggctttca gcccacaaat ggcgtgggct

1560 atcagcccta cagagtggtg gtgctgagct tcgaactgct gcatgcccct gccacagtgt

1620 gcggccctaa gaaaagcacc aatctcgtga agaacaaatg cgtgaacttc aacttcaacg

1680 gcctgaccgg caccggcgtg ctgacagaga gcaacaagaa gttcctgcca ttccagcagt

1740 ttggccggga tatcgccgat accacagacg ccgttagaga tccccagaca ctggaaatcc 1800 tggacatcac cccttgcagc ttcggcggag tgtctgtgat cacccctggc accaacacca

1860 gcaatcaggt ggcagtgctg taccagggcg tgaactgtac cgaagtgccc gtggccattc

1920 acgccgatca gctgacacct acatggcggg tgtactccac cggcagcaat gtgtttcaga

1980 ccagagccgg ctgtctgatc ggagccgagc acgtgaacaa tagctacgag tgcgacatcc

2040 ccatcggcgc tggaatctgc gccagctacc agacacagac aaacagcagg cggagagcca

2100 gaagcgtggc cagccagagc atcattgcct acacaatgtc tctgggcgcc gagaacagcg

2160 tggcctactc caacaactct atcgctatcc ccaccaactt caccatcagc gtgaccacag

2220 agatcctgcc tgtgtccatg accaagacca gcgtggactg caccatgtac atctgcggcg

2280 attccaccga gtgctccaac ctgctgctgc agtacggcag cttctgcacc cagctgaata

2340 gagccctgac agggatcgcc gtggaacagg acaagaacac ccaagaggtg ttcgcccaag

2400 tgaagcagat ctacaagacc cctcctatca aggacttcgg cggcttcaat ttcagccaga

2460 ttctgcccga tcctagcaag cccagcaagc ggagcttcat cgaggacctg ctgttcaaca

2520 aagtgacact ggccgacgcc ggcttcatca agcagtatgg cgattgtctg ggcgacattg

2580 ccgccaggga tctgatttgc gcccagaagt ttaacggact gacagtgctg cctcctctgc

2640 tgaccgatga gatgatcgcc cagtacacat ctgccctgct ggccggcaca atcacaagcg

2700 gctggacatt tggagcaggc gccgctctgc agatcccctt tgctatgcag atggcctacc

2760 ggttcaacgg catcggagtg acccagaatg tgctgtacga gaaccagaag ctgatcgcca

2820 accagttcaa cagcgccatc ggcaagatcc aggacagcct gagcagcaca gcaagcgccc

2880 tgggaaagct gcagaacgtg gtcaaccaga atgcccaggc actgaacacc ctggtcaagc

2940 agctgtcctc caacttcggc gccatcagct ctgtgctgaa cgatatcctg agcagactgg

3000 accctcctga ggccgaggtg cagatcgaca gactgatcac aggcagactg cagagcctcc

3060 agacatacgt gacccagcag ctgatcagag ccgccgagat tagagcctct gccaatctgg

3120 ccgccaccaa gatgtctgag tgtgtgctgg gccagagcaa gagagtggac ttttgcggca

3180 agggctacca cctgatgagc ttccctcagt ctgcccctca cggcgtggtg tttctgcacg

3240 tgacatatgt gcccgctcaa gagaagaatt tcaccaccgc tccagccatc tgccacgacg 3300 gcaaagccca ctttcctaga gaaggcgtgt tcgtgtccaa cggcacccat tggttcgtga

3360 cacagcggaa cttctacgag ccccagatca tcaccaccga caacaccttc gtgtctggca

3420 actgcgacgt cgtgatcggc attgtgaaca ataccgtgta cgaccctctg cagcccgagc

3480 tggacagctt caaagaggaa ctggacaagt actttaagaa ccacacaagc cccgacgtgg

3540 acctgggcga tatcagcgga atcaatgcca gcgtcgtgaa catccagaaa gagatcgacc

3600 ggctgaacga ggtggccaag aatctgaacg agagcctgat cgacctgcaa gaactgggga

3660 agtacgagca gtacatcaag tggccctggt acatctggct gggctttatc gccggactga

3720 ttgccatcgt gatggtcaca atcatgctgt gttgcatgac cagctgctgt agctgcctga

3780 agggctgttg tagctgtggc agctgctgca agttcgacga ggacgattct gagcccgtgc

3840 tgaagggcgt gaaactgcac tacacatgat gatttcacct ggtactgcat gcacgcaatg

3900 ctagctgccc ctttcccgtc ctgggtaccc cgagtctccc ccgacctcgg gtcccaggta

3960 tgctcccacc tccacctgcc ccactcacca cctctgctag ttccagacac ctcccaagca

4020 cgcagcaatg cagctcaaaa cgcttagcct agccacaccc ccacgggaaa cagcagtgat

4080 taacctttag caataaacga aagtttaact aagctatact aaccccaggg ttggtcaatt

4140 tcgtgccagc cacaccctgg agctagcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaagca

4200 tatgactaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaaaaa

4277

Sequence Number (ID) : 64

Length : 1270

Molecule Type : AA

Features Location/Qualif iers :

- source, 1 . . 1270

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA 120

TNWIKVCEF QFCNDPFLDV YYHKNNKSWM ESEFRVYSSA NNCTFEYVSQ PFLMDLEGKQ 180

GNFKNLREFV FKNIDGYFKI YSKHTPINLG RDLPQGFSAL EPLVDLPIGI NITRFQTLLA 240

LHRSYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL 300

KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFDEVFN ATRFASVYAW NRKRISNCVA 360 DYSVLYNFAP F FAFKCYGVS PTKLNDLCFT NVYADS FVIR GNEVSQIAPG QTGNIADYNY 420 KLPDDFTGCV IAWNSNKLDS KVGGNYNYLY RL FRKSNLKP F E RDISTEIY QAGNKPCNGV 480 AGFNCYFPLR SYGFRPTYGV GHQPYRWVL SF E LLHAPAT VCGPKKSTNL VKNKCVNFNF 540 NGLTGTGVLT ESNKKF LPFQ QFGRDIADTT DAVRDPQTLE I LDITPCSFG GVSVITPGTN 600 TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGC LIGA EYVNNSYECD 660 IPIGAGICAS YQTQTKSHRR ARSVASQSII AYTMSLGAEN SVAYSNNSIA IPTNFTISVT 720 TE I LPVSMTK TSVDCTMYIC GDSTECSNLL LQYGSFCTQL KRALTGIAVE QDKNTQEVFA 780 QVKQIYKTPP IKYFGGFNFS QI LPDPSKPS KRSFI EDLL F NKVTLADAGF IKQYGDCLGD 840 IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA 900 YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDWN HNAQALNTLV 960 KQLSSKFGAI SSVLNDI LSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEI RASAN

1020

LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGWF L HVTYVPAQEK NFTTAPAICH

1080

DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNTVYDPLQP

1140

ELDSFKEE LD KYFKNHTSPD VDLGDISGIN ASWNIQKE I DRLNEVAKNL NESLIDLQE L

1200

GKYEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC LKGCCSCGSC CKFDEDDS EP

1260

VLKGVKLHYT

1270

Sequence Number ( ID) : 65 Length : 3816

Molec ule Type : RNA

Featu res Location/Qualif iers :

- sou rce, 1 . . 3816

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgc ctctg gtgtc cagcc agtgtgtgaa c ctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatc cagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg c catccacgt gtccggcacc aatggcac ca agagattcga caac cccgtg 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtc caacat catcagaggc 300 tggatcttcg gcac cacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 tactaccaca agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acac ccctat caac ctcggc cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcacc ctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcgacga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aac cggaagc ggatcagcaa ttgcgtggcc 1080 gactactccg tgctgtacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggaaacgaag tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc

1320 aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg

1440 gcaggcttca actgctactt cccactgagg tcctacggct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct 2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 66

Length : 3816

Molecule Type : DNA

Features Location/Qualif iers :

- source, 1 . . 3816

> mol_type, other DNA > organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgtg 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 tactaccaca agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acacccctat caacctcggc cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcgacga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggaaacgaag tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc

1320 aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg

1440 gcaggcttca actgctactt cccactgagg tcctacggct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 67

Length : 4274

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1. .4274

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gtgctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctactacc 480 acaagaacaa caagagctgg atggaaagcg agttccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tatcaacctc ggccgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcga cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacttcgcc cccttcttcg cattcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggaaacg

1260 aagtgtcaca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc 1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caagctggac tccaaagtcg

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggcaggct

1500 tcaactgcta cttcccactg aggtcctacg gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc 2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa 4274

Sequence Number (ID) : 68

Length : 4274

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .4274

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gtgctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctactacc 480 acaagaacaa caagagctgg atggaaagcg agttccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tatcaacctc ggccgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcga cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacttcgcc cccttcttcg cattcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggaaacg

1260 aagtgtcaca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caagctggac tccaaagtcg

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggcaggct

1500 tcaactgcta cttcccactg aggtcctacg gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa

4274

Sequence Number (ID) : 69 Length : 1268

Molecule Type : AA

Features Location/Qualif iers :

- source, 1 . . 1268

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAISGTNG TKRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKTQ SLLIVNNATN 120

WIKVCEFQF CNDPFLDVYY HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN 180 FKNLRE FVFK NIDGYFKIYS KHTPINLGRD LPQGFSALEP LVDLPIGINI TRFQTLLALH 240 RSYLTPGDSS SGWTAGAAAY YVGYLQPRTF LLKYNENGTI TDAVDCALDP LS ETKCTLKS 300 FTVEKGIYQT SNFRVQPTES IVRFPNITNL CPFDEVFNAT RFASVYAWNR KRISNCVADY 360 SVLYNFAPF F AFKCYGVSPT KLNDLCFTNV YADSFVIRGN EVRQIAPGQT GNIADYNYKL 420 PDDFTGCVIA WNSNKLDSKV GGNYNYRYRL FRKSNLKPF E RDISTE IYQA GNKPCNGVAG 480 VNCYFPLQSY GFRPTYGVGH QPYRWVLSF E L LHAPATVC GPKKSTNLVK NKCVNFNFNG 540 LTGTGVLTES NKKF LPFQQF GRDIADTTDA VRDPQTLEI L DITPCS FGGV SVITPGTNTS 600 NQVAVLYQGV NCTEVPVAIH ADQLTPTWRV YSTGSNVFQT RAGCLIGAEY VNNSYECDIP 660 IGAGICASYQ TQTKSHRRAR SVASQSIIAY TMSLGAENSV AYSNNSIAI P TNFTISVTTE 720 ILPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV 780 KQIYKTPPIK YFGGFNFSQI LPDPSKPSKR SF I EDLLFNK VTLADAGFIK QYGDC LGDIA 840 ARDLICAQKF NGLTVLPPL L TDEMIAQYTS AL LAGTITSG WTFGAGAALQ IPFAMQMAYR 900 FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DS LSSTASAL GKLQDWNHN AQALNTLVKQ 960 LSSKFGAISS VLNDI LSRLD PPEAEVQIDR LITGRLQSLQ TYVTQQLIRA AE IRASANLA

1020

ATKMS ECVLG QSKRVDFCGK GYHLMSFPQS APHGVVFLHV TYVPAQEKNF TTAPAICHDG

1080 KAHFPREGVF VSNGTHWFVT QRNFYEPQII TTDNTFVSGN CDWIGIVNN TVYDPLQPE L

1140

DSFKE E LDKY FKNHTSPDVD LGDISGINAS VVNIQKEIDR LNEVAKNLNE S LIDLQE LGK

1200

YEQYIKWPWY IWLGFIAGLI AIVMVTIMLC CMTSCCSCLK GCCSCGSCCK FDEDDSEPVL

1260 KGVKLHYT

1268

Sequence Number ( ID) : 70

Length : 3810

Molec ule Type : RNA

Featu res Location/Qualif iers :

- sou rce, 1 . . 3810

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgc ctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacc caggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg c catctccgg caccaatggc accaagagat tcgacaaccc cgtgctgc cc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtc ca acatcatcag aggctggatc 300 ttcggcac ca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttc cagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggc cgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcc catcgg catcaacatc acccggtttc agacactgct ggcc ctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 agattcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgcggc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number (ID) : 71 Length : 3810

Molecule Type : DNA Features Location/Qualifiers :

- source, 1 . . 3810

> mol type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 agattcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgcggc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac 1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac 3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number ( ID) : 72

Length : 4268

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1 . .4268

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatctc cggcaccaat ggcaccaaga gattcgacaa ccccgtgctg cccttcaacg 300 acggggtgta ctttgccagc accgagaagt ccaacatcat cagaggctgg atcttcggca 360 ccacactgga cagcaagacc cagagcctgc tgatcgtgaa caacgccacc aacgtggtca 420 tcaaagtgtg cgagttccag ttctgcaacg accccttcct ggacgtctac taccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcaa cctcggccgg gatctgcctc agggcttctc tgctctggaa cccctggtgg 720 atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg cacagaagct 780 acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct tactatgtgg 840 gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc atcaccgacg 900 ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag tccttcaccg 960 tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa tccatcgtgc

1020 ggttccccaa tatcaccaat ctgtgcccct tcgacgaggt gttcaatgcc accagattcg

1080 cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac tactccgtgc

1140 tgtacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct accaagctga

1200 acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga aacgaagtgc

1260 ggcagattgc ccctggacag acaggcaaca tcgccgacta caactacaag ctgcccgacg

1320 acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa gtcggcggca

1380 actacaatta caggtaccgg ctgttccgga agtccaatct gaagcccttc gagcgggaca

1440 tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca ggcgtgaact

1500 gctacttccc actgcagtcc tacggcttta ggcccacata cggcgtgggc caccagccct

1560 acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg tgcggcccta

1620 agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac ggcctgaccg

1680 gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag tttggccggg

1740 atatcgccga taccacagac gccgttagag atccccagac actggaaatc ctggacatca

1800 ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc agcaatcagg

1860 tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt cacgccgatc

1920 agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag accagagccg

1980 gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc cccatcggcg

2040 ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc agaagcgtgg

2100 ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc gtggcctact

2160 ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca gagatcctgc

2220 ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc gattccaccg

2280 agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa agagccctga

2340 cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa gtgaagcaga

2400 tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag attctgcccg

2460 atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac aaagtgacac

2520 tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt gccgccaggg

2580 atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg ctgaccgatg

2640 agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc ggctggacat

2700 ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac cggttcaacg

2760 gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc aaccagttca

2820 acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc ctgggaaagc

2880 tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag cagctgtcct

2940 ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg gaccctcctg

3000 aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc cagacatacg

3060 tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg gccgccacca

3120 agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc aagggctacc

3180 acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac gtgacatatg

3240 tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac ggcaaagccc

3300 actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg acacagcgga

3360 acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc aactgcgacg

3420 tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag ctggacagct

3480 tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg gacctgggcg

3540 atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac cggctgaacg

3600 aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg aagtacgagc

3660 agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg attgccatcg

3720 tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg aagggctgtt

3780 gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg ctgaagggcg

3840 tgaaactgca ctacacatga tgactcgagc tggtactgca tgcacgcaat gctagctgcc

3900 cctttcccgt cctgggtacc ccgagtctcc cccgacctcg ggtcccaggt atgctcccac

3960 ctccacctgc cccactcacc acctctgcta gttccagaca cctcccaagc acgcagcaat

4020 gcagctcaaa acgcttagcc tagccacacc cccacgggaa acagcagtga ttaaccttta

4080 gcaataaacg aaagtttaac taagctatac taaccccagg gttggtcaat ttcgtgccag

4140 ccacaccctg gagctagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagc atatgactaa

4200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaa

4268

Sequence Number (ID) : 73

Length : 4268

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . .4268

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatctc cggcaccaat ggcaccaaga gattcgacaa ccccgtgctg cccttcaacg 300 acggggtgta ctttgccagc accgagaagt ccaacatcat cagaggctgg atcttcggca 360 ccacactgga cagcaagacc cagagcctgc tgatcgtgaa caacgccacc aacgtggtca 420 tcaaagtgtg cgagttccag ttctgcaacg accccttcct ggacgtctac taccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcaa cctcggccgg gatctgcctc agggcttctc tgctctggaa cccctggtgg 720 atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg cacagaagct 780 acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct tactatgtgg 840 gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc atcaccgacg 900 ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag tccttcaccg 960 tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa tccatcgtgc

1020 ggttccccaa tatcaccaat ctgtgcccct tcgacgaggt gttcaatgcc accagattcg

1080 cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac tactccgtgc

1140 tgtacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct accaagctga

1200 acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga aacgaagtgc

1260 ggcagattgc ccctggacag acaggcaaca tcgccgacta caactacaag ctgcccgacg

1320 acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa gtcggcggca

1380 actacaatta caggtaccgg ctgttccgga agtccaatct gaagcccttc gagcgggaca

1440 tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca ggcgtgaact

1500 gctacttccc actgcagtcc tacggcttta ggcccacata cggcgtgggc caccagccct

1560 acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg tgcggcccta 1620 agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac ggcctgaccg

1680 gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag tttggccggg

1740 atatcgccga taccacagac gccgttagag atccccagac actggaaatc ctggacatca

1800 ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc agcaatcagg

1860 tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt cacgccgatc

1920 agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag accagagccg

1980 gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc cccatcggcg

2040 ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc agaagcgtgg

2100 ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc gtggcctact

2160 ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca gagatcctgc

2220 ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc gattccaccg

2280 agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa agagccctga

2340 cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa gtgaagcaga

2400 tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag attctgcccg

2460 atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac aaagtgacac

2520 tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt gccgccaggg

2580 atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg ctgaccgatg

2640 agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc ggctggacat

2700 ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac cggttcaacg

2760 gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc aaccagttca

2820 acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc ctgggaaagc

2880 tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag cagctgtcct

2940 ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg gaccctcctg

3000 aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc cagacatacg

3060 tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg gccgccacca 3120 agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc aagggctacc

3180 acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac gtgacatatg

3240 tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac ggcaaagccc

3300 actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg acacagcgga

3360 acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc aactgcgacg

3420 tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag ctggacagct

3480 tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg gacctgggcg

3540 atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac cggctgaacg

3600 aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg aagtacgagc

3660 agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg attgccatcg

3720 tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg aagggctgtt

3780 gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg ctgaagggcg

3840 tgaaactgca ctacacatga tgactcgagc tggtactgca tgcacgcaat gctagctgcc

3900 cctttcccgt cctgggtacc ccgagtctcc cccgacctcg ggtcccaggt atgctcccac

3960 ctccacctgc cccactcacc acctctgcta gttccagaca cctcccaagc acgcagcaat

4020 gcagctcaaa acgcttagcc tagccacacc cccacgggaa acagcagtga ttaaccttta

4080 gcaataaacg aaagtttaac taagctatac taaccccagg gttggtcaat ttcgtgccag

4140 ccacaccctg gagctagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagc atatgactaa

4200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaa

4268

Sequence Number (ID) : 74

Length : 1268

Molecule Type : AA

Features Location/Qualif iers :

- source, 1 . . 1268

> mol_type, protein

> organism, synthetic construct Residues : MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LF LPF FSNVT 60 WFHAISGTNG TKRFDNPVLP FNDGVYFAST EKSNII RGWI FGTTLDSKTQ SL LIVNNATN 120 WIKVC EFQF CNDPFLDVYY HKNNKSWMES E F RVYSSANN CTF EYVSQPF LMDLEGKQGN 180 FKNLRE FVFK NIDGYFKIYS KHTPINLGRD LPQGFSALEP LVDLPIGINI TRFQTLLALH 240 RSYLTPGDSS SGWTAGAAAY YVGYLQPRTF LLKYNENGTI TDAVDCALDP LS ETKCTLKS 300 FTVEKGIYQT SNFRVQPTES IVRFPNITNL CPFDEVFNAT RFASVYAWNR KRISNCVADY 360 SVLYNFAPF F AFKCYGVSPT KLNDLCFTNV YADSFVIRGN EVSQIAPGQT GNIADYNYKL 420 PDDFTGCVIA WNSNKLDSKV GGNYNYRYRL FRKSNLKPF E RDISTEIYQA GNKPCNGVAG 480 VNCYF PLQSY GFRPTYGVGH QPYRVWLSF E L LHAPATVC GPKKSTNLVK NKCVNFNFNG 540 LTGTGVLTES NKKF LPFQQF GRDIADTTDA VRDPQTLEI L DITPCSFGGV SVITPGTNTS 600 NQVAVLYQGV NCTEVPVAIH ADQLTPTWRV YSTGSNVFQT RAGCLIGAEY VNNSYECDIP 660 IGAGICASYQ TQTKSHRRAR SVASQSIIAY TMSLGAENSV AYSNNSIAI P TNFTISVTTE 720 ILPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV 780 KQIYKTPPIK YFGGFNFSQI LPDPSKPSKR SF I EDLLFNK VTLADAGFIK QYGDC LGDIA 840 ARDLICAQKF NGLTVLPPL L TDEMIAQYTS ALLAGTITSG WTFGAGAALQ I PFAMQMAYR 900 FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTASAL GKLQDWNHN AQALNTLVKQ 960 LSSKFGAISS VLNDI LSRLD PPEAEVQIDR LITGRLQS LQ TYVTQQLIRA AE IRAS AN LA

1020

ATKMS ECVLG QSKRVDFCGK GYHLMSFPQS APHGVVFLHV TYVPAQEKNF TTAPAICHDG

1080

KAHFPREGVF VSNGTHWFVT QRNFYEPQII TTDNTFVSGN CDWIGIVNN TVYDPLQPEL

1140 DSFKE E LDKY FKNHTSPDVD LGDISGINAS VVNIQKEIDR LNEVAKNLNE S LIDLQE LGK

1200 YEQYIKWPWY IWLGFIAGLI AIVMVTIMLC CMTSCCSC LK GCCSCGSCCK FDEDDSEPVL

1260 KGVKLHYT

1268

Sequence Number ( ID) : 75

Length : 3810

Molecule Type : RNA Features Location/Qualifiers :

- source, 1 . . 3810

> mol type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacaga gctacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacc caggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgc cc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtc ca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacc cag agc ctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtgtactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgc ccatcgg catcaacatc acc cggtttc agacactgct ggccctgcac 720 agaagctacc tgacac ctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 agattcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gccttcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgagcc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggccggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatatgg cgtgggccat

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaagaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt 2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810 Sequence Number (ID) : 76

Length : 3810

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . . 3810

> mol_type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacaga gctacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtgtactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 agattcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gccttcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgagcc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggccggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatatgg cgtgggccat

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaagaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number ( ID) : 77

Length : 1268

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 1268

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LF LPF FSNVT 60

WFHAISGTNG TKRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKTQ SLLIVNNATN 120

WIKVCEFQF CNDPFLDVYY HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN 180

FKNLREFVFK NIDGYFKIYS KHTPINLGRD LPQGFSALEP LVDLPIGINI TRFQTLLALH 240

RSYLTPGDSS SGWTAGAAAY YVGYLQPRTF LLKYNENGTI TDAVDCALDP LSETKCTLKS 300

FTVEKGIYQT SNFRVQPTES IVRFPNITNL CPFDEVFNAT RFASVYAWNR KRISNCVADY 360

SVLYNFAPF F AFKCYGVSPT KLNDLCFTNV YADSFVIRGN EVRQIAPGQT GNIADYNYKL 420

PDDFTGCVIA WNSNKLDSKV GGNYNYRYRL FRKSNLKPF E RDISTEIYQA GNKPCNGVAG 480

VNCYFPLQSY GFRPTYGVGH QPYRVWLSF ELLHAPATVC GPKKSTNLVK NKCVNFNFNG 540

LTGTGVLTES NKKFLPFQQF GRDIADTTDA VRDPQTLEI L DITPCSFGGV SVITPGTNTS 600

NQVAVLYQGV NCTEVPVAIH ADQLTPTWRV YSTGSNVFQT RAGCLIGAEY VNNSYECDIP 660

IGAGICASYQ TQTKSHRRAR SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVTTE 720

ILPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV 780

KQIYKTPPIK YFGGFNFSQI LPDPSKPSKR SFIEDLLFNK VTLADAGFIK QYGDCLGDIA 840

ARDLICAQKF NGLTVLPPLL TDEMIAQYTS ALLAGTITSG WTFGAGAALQ IPFAMQMAYR 900

FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTASAL GKLQDWNHN AQALNTLVKQ 960

LSSKFGAISS VLNDILSRLD PPEAEVQIDR LITGRLQSLQ TYVTQQLIRA AEIRASANLA

1020

ATKMSECVLG QSKRVDFCGK GYHLMSFPQS APHGWFLHV TYVPAQEKNF TTAPAICHDG

1080

KAHFPREGVF VSNGTHWFVT QRNFYEPQII TTDNTFVSGN CDVVIGIVNN TVYDPLQPEL 1140

DSFKEE LDKY FKNHTSPDVD LGDISGINAS WNIQKEIDR LNEVAKNLNE SLIDLQELGK

1200

YEQYIKWPWY IWLGFIAGLI AIVMVTIMLC CMTSCCSCLK GCCSCGSCCK FDEDDSEPVL

1260

KGVKLHYT

1268

Sequence Number (ID) : 78

Length : 3810

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1 . . 3810

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 agattcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgcggc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number (ID) : 79

Length : 3810

Molecule Type : DNA Features Location/Qualifiers :

- source, 1 . . 3810

> mol type, other DNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 agattcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgcggc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt 2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810 Sequence Number (ID): 80 Length: 1270 Molecule Type: AA Features Location/Qualifiers: - source, 1..1270

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA 120

TNVVIKVCEF QFCNDPFLDV YYHENNKSRM ESELRVYSSA NNCTFEYVSQ PFLMDLEGKQ 180

GNFKNLREFV FKNIDGYFKI YSKHTPVNLG RDLPQGFSAL EPLVDLPIGI NITRFQTLLA 240

LHRSYLTPGD SSSSWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL 300

KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFHEVFN ATRFASVYAW NRKRISNCVA 360

DYSVLYNFAP FFAFKCYGVS PTKLNDLCFT NVYADSFVIR GNEVSQIAPG QTGNIADYNY 420

KLPDDFTGCV IAWNSNKLDS KVSGNYNYLY RLFRKSKLKP FERDISTEIY QAGNKPCNGV 480

AGFNCYFPLQ SYGFRPTYGV GHQPYRVWL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF 540

NGLTGTGVLT ESNKKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN 600

TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EYVNNSYECD 660

IPIGAGICAS YQTQTKSHRR ARSVASQSII AYTMSLGAEN SVAYSNNSIA IPTNFTISVT 720

TEILPVSMTK TSVDCTMYIC GDSTECSNLL LQYGSFCTQL KRALTGIAVE QDKNTQEVFA 780

QVKQIYKTPP IKYFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD 840

IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA 900

YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDWN HNAQALNTLV 960

KQLSSKFGAI SSVLNDILSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN

1020

LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGWFL HVTYVPAQEK NFTTAPAICH

1080

DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNTVYDPLQP

1140

ELDSFKEELD KYFKNHTSPD VDLGDISGIN ASWNIQKEI DRLNEVAKNL NESLIDLQEL

1200

GKYEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC LKGCCSCGSC CKFDEDDSEP

1260

VLKGVKLHYT

1270

Sequence Number (ID): 81

Length: 3816

Molecule Type: RNA

Features Location/Qualifiers:

- source, 1. .3816

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgtg 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 tactaccacg agaacaacaa gagcaggatg gaaagcgagc tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acacccctgt gaacctcggc cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagca gctggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggaaacgaag tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc

1320 aaagtcagcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg

1440 gcaggcttca actgctactt cccactgcag tcctacggct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc 2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga 3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 82

Length : 3816

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . . 3816

> mol_type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgtg 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 tactaccacg agaacaacaa gagcaggatg gaaagcgagc tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acacccctgt gaacctcggc cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagca gctggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggaaacgaag tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc

1320 aaagtcagcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg

1440 gcaggcttca actgctactt cccactgcag tcctacggct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 83

Length : 4273

Molecule Type : RNA Features Location/Qualifiers :

- source, 1. .4273

> mol type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gtgctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctactacc 480 acgagaacaa caagagcagg atggaaagcg agctccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tgtgaacctc ggccgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcagctggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcca cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacttcgcc cccttcttcg cattcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggaaacg

1260 aagtgtcaca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caagctggac tccaaagtca

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caagctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggcaggct

1500 tcaactgcta cttcccactg cagtcctacg gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga 2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta 3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaa

4273

Sequence Number (ID) : 84 Length : 4273

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . .4273

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gtgctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctactacc 480 acgagaacaa caagagcagg atggaaagcg agctccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tgtgaacctc ggccgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcagctggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcca cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacttcgcc cccttcttcg cattcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggaaacg

1260 aagtgtcaca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caagctggac tccaaagtca

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caagctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggcaggct

1500 tcaactgcta cttcccactg cagtcctacg gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaa

4273

Sequence Number (ID): 85

Length: 1270

Molecule Type: AA

Features Location/Qualifiers :

- source, 1. .1270

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA 120

TNVVIKVCEF QFCNDPFLDV YYHENNKSRM ESELRVYSSA NNCTFEYVSQ PFLMDLEGKQ 180

GNFKNLREFV FKNIDGYFKI YSKHTPVNLG RDLPQGFSAL EPLVDLPIGI NITRFQTLLA 240

LHRSYLTPGD SSSSWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL 300

KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFHEVFN ATTFASVYAW NRKRISNCVA 360

DYSVLYNFAP FFAFKCYGVS PTKLNDLCFT NVYADSFVIR GNEVSQIAPG QTGNIADYNY 420

KLPDDFTGCV IAWNSNKLDS KVSGNYNYLY RLFRKSKLKP FERDISTEIY QAGNKPCNGV 480

AGSNCYFPLQ SYGFRPTYGV GHQPYRVWL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF 540

NGLTGTGVLT ESNKKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN 600

TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EYVNNSYECD 660

IPIGAGICAS YQTQTKSHRR ARSVASQSII AYTMSLGAEN SVAYSNNSIA IPTNFTISVT 720

TEILPVSMTK TSVDCTMYIC GDSTECSNLL LQYGSFCTQL KRALTGIAVE QDKNTQEVFA 780

QVKQIYKTPP IKYFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD 840

IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA 900

YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDWN HNAQALNTLV 960

KQLSSKFGAI SSVLNDILSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN

1020

LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGWFL HVTYVPAQEK NFTTAPAICH

1080

DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDWIGIV NNTVYDPLQP

1140

ELDSFKEELD KYFKNHTSPD VDLGDISGIN ASWNIQKEI DRLNEVAKNL NESLINLQEL

1200

GKYEQYIKWP WYIWLGFIAG LIAIVMVTIM LCCMTSCCSC LKGCCSCGSC CKFDEDDSEP

1260

VLKGVKLHYT

1270

Sequence Number (ID): 86

Length: 3816

Molecule Type: RNA

Features Location/Qualifiers:

- source, 1. .3816

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgtg 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 tactaccacg agaacaacaa gagcaggatg gaaagcgagc tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acacccctgt gaacctcggc cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagca gctggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat

1020 gccaccacct tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggaaacgaag tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc

1320 aaagtcagcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg

1440 gcaggcagca actgctactt cccactgcag tcctacggct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcaacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 87

Length : 3816

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. . 3816

> mol_type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgtg 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 tactaccacg agaacaacaa gagcaggatg gaaagcgagc tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acacccctgt gaacctcggc cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagca gctggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat

1020 gccaccacct tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggaaacgaag tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc

1320 aaagtcagcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg 1440 gcaggcagca actgctactt cccactgcag tcctacggct ttaggcccac atacggcgtg

1500 ggccaccagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aaaagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga 2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcaacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 88

Length : 4273

Molecule Type : RNA

Features Location/Qualif iers :

- source, 1. .4273

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gtgctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctactacc 480 acgagaacaa caagagcagg atggaaagcg agctccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tgtgaacctc ggccgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcagctggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcca cgaggtgttc aatgccacca

1080 ccttcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacttcgcc cccttcttcg cattcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggaaacg

1260 aagtgtcaca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caagctggac tccaaagtca

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caagctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggcaggca

1500 gcaactgcta cttcccactg cagtcctacg gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcaa cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaa

4273

Sequence Number (ID) : 89

Length : 4273

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .4273

> mol_type, other DNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gtgctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctactacc 480 acgagaacaa caagagcagg atggaaagcg agctccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tgtgaacctc ggccgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcagctggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcca cgaggtgttc aatgccacca

1080 ccttcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caacttcgcc cccttcttcg cattcaagtg ctacggcgtg tcccctacca 1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggaaacg

1260 aagtgtcaca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caagctggac tccaaagtca

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caagctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcaacaagcc ttgtaacggc gtggcaggca

1500 gcaactgcta cttcccactg cagtcctacg gctttaggcc cacatacggc gtgggccacc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagtacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa gagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaaaagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagt acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct 2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccacaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa gttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcaa cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat 4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4260 aaaaaaaaaa aaa 4273

Sequence Number (ID): 90

Length: 1268

Molecule Type: AA

Features Location/Qualifiers:

- source, 1. .1268

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAISGTNG TKRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKTQ SLLIVNNATN 120

WIKVCEFQF CNDPFLDVYY HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN 180

FKNLREFVFK NIDGYFKIYS KHTPINLGRD LPQGFSALEP LVDLPIGINI TRFQTLLALH 240

RSYLTPGDSS SGWTAGAAAY YVGYLQPRTF LLKYNENGTI TDAVDCALDP LSETKCTLKS 300

FTVEKGIYQT SNFRVQPTES IVRFPNITNL CPFDEVFNAT TFASVYAWNR KRISNCVADY 360

SVLYNFAPFF AFKCYGVSPT KLNDLCFTNV YADSFVIRGN EVRQIAPGQT GNIADYNYKL 420

PDDFTGCVIA WNSNKLDSKV GGNYNYRYRL FRKSNLKPFE RDISTEIYQA GNKPCNGVAG 480

VNCYFPLQSY GFRPTYGVGH QPYRWVLSF ELLHAPATVC GPKKSTNLVK NKCVNFNFNG 540

LTGTGVLTES NKKFLPFQQF GRDIADTTDA VRDPQTLEIL DITPCSFGGV SVITPGTNTS 600

NQVAVLYQGV NCTEVPVAIH ADQLTPTWRV YSTGSNVFQT RAGCLIGAEY VNNSYECDIP 660

IGAGICASYQ TQTKSHRRAR SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVTTE 720

ILPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV 780

KQIYKTPPIK YFGGFNFSQI LPDPSKPSKR SFIEDLLFNK VTLADAGFIK QYGDCLGDIA 840

ARDLICAQKF NGLTVLPPLL TDEMIAQYTS ALLAGTITSG WTFGAGAALQ IPFAMQMAYR 900

FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTASAL GKLQDWNHN AQALNTLVKQ 960

LSSKFGAISS VLNDILSRLD PPEAEVQIDR LITGRLQSLQ TYVTQQLIRA AEIRASANLA

1020

ATKMSECVLG QSKRVDFCGK GYHLMSFPQS APHGWFLHV TYVPAQEKNF TTAPAICHDG

1080

KAHFPREGVF VSNGTHWFVT QRNFYEPQII TTDNTFVSGN CDWIGIVNN TVYDPLQPEL

1140

DSFKEELDKY FKNHTSPDVD LGDISGINAS VVNIQKEIDR LNEVAKNLNE SLIDLQELGK

1200

YEQYIKWPWY IWLGFIAGLI AIVMVTIMLC CMTSCCSCLK GCCSCGSCCK FDEDDSEPVL

1260 KGVKLHYT 1268

Sequence Number (ID): 91

Length: 3810

Molecule Type: RNA

Features Location/Qualifiers:

- source, 1..3810

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 accttcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgcggc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc 1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac 3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number (ID) : 92

Length : 3810

Molecule Type : DNA Features Location/Qualifiers :

- source, 1 . . 3810

> mol type, other DNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 accttcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgcggc agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaaagtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaatctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number (ID) : 93

Length : 4267

Molecule Type : RNA

Features Location/Qualif iers :

- source, 1. .4267

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatctc cggcaccaat ggcaccaaga gattcgacaa ccccgtgctg cccttcaacg 300 acggggtgta ctttgccagc accgagaagt ccaacatcat cagaggctgg atcttcggca 360 ccacactgga cagcaagacc cagagcctgc tgatcgtgaa caacgccacc aacgtggtca 420 tcaaagtgtg cgagttccag ttctgcaacg accccttcct ggacgtctac taccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcaa cctcggccgg gatctgcctc agggcttctc tgctctggaa cccctggtgg 720 atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg cacagaagct 780 acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct tactatgtgg 840 gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc atcaccgacg 900 ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag tccttcaccg 960 tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa tccatcgtgc

1020 ggttccccaa tatcaccaat ctgtgcccct tcgacgaggt gttcaatgcc accaccttcg

1080 cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac tactccgtgc

1140 tgtacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct accaagctga

1200 acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga aacgaagtgc

1260 ggcagattgc ccctggacag acaggcaaca tcgccgacta caactacaag ctgcccgacg

1320 acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa gtcggcggca

1380 actacaatta caggtaccgg ctgttccgga agtccaatct gaagcccttc gagcgggaca

1440 tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca ggcgtgaact

1500 gctacttccc actgcagtcc tacggcttta ggcccacata cggcgtgggc caccagccct

1560 acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg tgcggcccta

1620 agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac ggcctgaccg

1680 gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag tttggccggg

1740 atatcgccga taccacagac gccgttagag atccccagac actggaaatc ctggacatca

1800 ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc agcaatcagg

1860 tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt cacgccgatc

1920 agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag accagagccg

1980 gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc cccatcggcg

2040 ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc agaagcgtgg

2100 ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc gtggcctact

2160 ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca gagatcctgc 2220 ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc gattccaccg

2280 agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa agagccctga

2340 cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa gtgaagcaga

2400 tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag attctgcccg

2460 atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac aaagtgacac

2520 tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt gccgccaggg

2580 atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg ctgaccgatg

2640 agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc ggctggacat

2700 ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac cggttcaacg

2760 gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc aaccagttca

2820 acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc ctgggaaagc

2880 tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag cagctgtcct

2940 ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg gaccctcctg

3000 aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc cagacatacg

3060 tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg gccgccacca

3120 agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc aagggctacc

3180 acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac gtgacatatg

3240 tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac ggcaaagccc

3300 actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg acacagcgga

3360 acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc aactgcgacg

3420 tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag ctggacagct

3480 tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg gacctgggcg

3540 atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac cggctgaacg

3600 aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg aagtacgagc

3660 agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg attgccatcg 3720 tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg aagggctgtt

3780 gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg ctgaagggcg

3840 tgaaactgca ctacacatga tgactcgagc tggtactgca tgcacgcaat gctagctgcc

3900 cctttcccgt cctgggtacc ccgagtctcc cccgacctcg ggtcccaggt atgctcccac

3960 ctccacctgc cccactcacc acctctgcta gttccagaca cctcccaagc acgcagcaat

4020 gcagctcaaa acgcttagcc tagccacacc cccacgggaa acagcagtga ttaaccttta

4080 gcaataaacg aaagtttaac taagctatac taaccccagg gttggtcaat ttcgtgccag

4140 ccacaccctg gagctagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagc atatgactaa

4200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaa

4267

Sequence Number (ID) : 94 Length : 4267

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . .4267

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatctc cggcaccaat ggcaccaaga gattcgacaa ccccgtgctg cccttcaacg 300 acggggtgta ctttgccagc accgagaagt ccaacatcat cagaggctgg atcttcggca 360 ccacactgga cagcaagacc cagagcctgc tgatcgtgaa caacgccacc aacgtggtca 420 tcaaagtgtg cgagttccag ttctgcaacg accccttcct ggacgtctac taccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcaa cctcggccgg gatctgcctc agggcttctc tgctctggaa cccctggtgg 720 atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg cacagaagct 780 acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct tactatgtgg 840 gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc atcaccgacg 900 ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag tccttcaccg 960 tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa tccatcgtgc

1020 ggttccccaa tatcaccaat ctgtgcccct tcgacgaggt gttcaatgcc accaccttcg

1080 cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac tactccgtgc

1140 tgtacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct accaagctga

1200 acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga aacgaagtgc

1260 ggcagattgc ccctggacag acaggcaaca tcgccgacta caactacaag ctgcccgacg

1320 acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa gtcggcggca

1380 actacaatta caggtaccgg ctgttccgga agtccaatct gaagcccttc gagcgggaca

1440 tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca ggcgtgaact

1500 gctacttccc actgcagtcc tacggcttta ggcccacata cggcgtgggc caccagccct

1560 acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg tgcggcccta

1620 agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac ggcctgaccg

1680 gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag tttggccggg

1740 atatcgccga taccacagac gccgttagag atccccagac actggaaatc ctggacatca

1800 ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc agcaatcagg

1860 tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt cacgccgatc

1920 agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag accagagccg

1980 gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc cccatcggcg

2040 ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc agaagcgtgg

2100 ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc gtggcctact

2160 ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca gagatcctgc

2220 ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc gattccaccg

2280 agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa agagccctga

2340 cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa gtgaagcaga

2400 tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag attctgcccg

2460 atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac aaagtgacac

2520 tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt gccgccaggg

2580 atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg ctgaccgatg

2640 agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc ggctggacat

2700 ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac cggttcaacg

2760 gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc aaccagttca

2820 acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc ctgggaaagc

2880 tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag cagctgtcct

2940 ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg gaccctcctg

3000 aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc cagacatacg

3060 tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg gccgccacca

3120 agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc aagggctacc

3180 acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac gtgacatatg

3240 tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac ggcaaagccc

3300 actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg acacagcgga

3360 acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc aactgcgacg

3420 tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag ctggacagct

3480 tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg gacctgggcg

3540 atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac cggctgaacg

3600 aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg aagtacgagc

3660 agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg attgccatcg

3720 tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg aagggctgtt

3780 gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg ctgaagggcg

3840 tgaaactgca ctacacatga tgactcgagc tggtactgca tgcacgcaat gctagctgcc

3900 cctttcccgt cctgggtacc ccgagtctcc cccgacctcg ggtcccaggt atgctcccac

3960 ctccacctgc cccactcacc acctctgcta gttccagaca cctcccaagc acgcagcaat

4020 gcagctcaaa acgcttagcc tagccacacc cccacgggaa acagcagtga ttaaccttta

4080 gcaataaacg aaagtttaac taagctatac taaccccagg gttggtcaat ttcgtgccag 4140 ccacaccctg gagctagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagc atatgactaa

4200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaa 4267

Sequence Number (ID): 95 Length: 1269 Molecule Type: AA Features Location/Qualif iers : - source, 1..1269

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAIHVSGT NGTKRFDNPA LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA 120

TNWIKVCEF QFCNDPFLDV YQKNNKSWME SEFRVYSSAN NCTFEYVSQP FLMDLEGKEG 180

NFKNLREFVF KNIDGYFKIY SKHTPINLER DLPQGFSALE PLVDLPIGIN ITRFQTLLAL 240

HRSYLTPGDS SSGWTAGAAA YYVGYLQPRT FLLKYNENGT ITDAVDCALD PLSETKCTLK 300

SFTVEKGIYQ TSNFRVQPTE SIVRFPNITN LCPFHEVFNA TTFASVYAWN RKRISNCVAD 360

YSVIYNFAPF FAFKCYGVSP TKLNDLCFTN VYADSFVIRG NEVSQIAPGQ TGNIADYNYK 420

LPDDFTGCVI AWNSNKLDSK PSGNYNYLYR LFRKSKLKPF ERDISTEIYQ AGNKPCNGVA 480

GSNCYSPLQS YGFRPTYGVG HQPYRWVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN 540

GLTGTGVLTE SNKKFLPFQQ FGRDIADTTD AVRDPQTLEI LDITPCSFGG VSVITPGTNT 600

SNQVAVLYQG VNCTEVPVAI HADQLTPTWR VYSTGSNVFQ TRAGCLIGAE YVNNSYECDI 660

PIGAGICASY QTQTKSHRRA RSVASQSIIA YTMSLGAENS VAYSNNSIAI PTNFTISVTT 720

EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ 780

VKQIYKTPPI KYFGGFNFSQ ILPDPSKPSK RSFIEDLLFN KVTLADAGFI KQYGDCLGDI 840

AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAAL QIPFAMQMAY 900

RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QDSLSSTASA LGKLQDWNH NAQALNTLVK 960

QLSSKFGAIS SVLNDILSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL

1020 AATKMSECVL GQSKRVDFCG KGYHLMSFPQ SAPHGWFLH VTYVPAQEKN FTTAPAICHD

1080 GKAHFPREGV FVSNGTHWFV TQRNFYEPQI ITTDNTFVSG NCDVVIGIVN NTVYDPLQPE

1140

LDSFKEELDK YFKNHTSPDV DLGDISGINA SWNIQKEID RLNEVAKNLN ESLIDLQELG

1200 KYEQYIKWPW YIIAILGFIAGL IAIVMVTIML CCMTSCCSCL KGCCSCGSCC KFDEDDSEPV

1260 LKGVKLHYT

1269

Sequence Number (ID): 96

Length: 3813

Molecule Type: RNA

Features Location/Qualif iers : - source, 1. . 3813

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcacct tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg 720 cacagaagct acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggcagcaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number (ID) : 97 Length : 3813

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .3813

> mol_type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcacct tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg 720 cacagaagct acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag 1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggcagcaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc 2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number ( ID) : 98

Length : 4270

Molecule Type : RNA

Features Location/Qualif iers :

- source, 1. .4270

> mol_type, other RNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcagca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270

Sequence Number (ID) : 99 Length : 4270

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .4270

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg 1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcagca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga 2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc 4020 aatgcagctc aaaacgctta gc ctagccac ac ccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270

Sequence Number ( ID) : 100 Length : 1268 Molecule Type : AA Features Location/Qualifiers : - source, 1 . . 1268

> mol_type, protein

> organism, synthetic construct Res idues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LF LPF FSNVT 60

WFHAISGTNG TKRFDNPVLP FNDGVYFAST EKSNII RGWI FGTTLDSKTQ SL LIVNNATN 120

WIKVC EFQF CNDPFLDVYY HKNNKSWMES E F RVYSSANN CTF EYVSQPF LMDLEGKQGN 180

FKNLRE FVFK NIDGYFKIYS KHTPINLGRD LPQGFSALEP LVDLPIGINI TRFQTLLALH 240

RSYLTPGDSS SGWTAGAAAY YVGYLQPRTF LLKYNENGTI TDAVDCALDP LS ETKCTLKS 300

FTVEKGIYQT SNFRVQPTES IVRFPNITNL CPFDEVFNAT TFASVYAWNR KRISNCVADY 360

SVLYNFAPF F AFKCYGVSPT KLNDLCFTNV YADSFVIRGN EVSQIAPGQT GNIADYNYKL 420

PDDFTGCVIA WNSNKLDSTV GGNYNYRYRL F RKSKLKPF E RDISTEIYQA GNKPCNGVAG 480

VNCYF PLQSY GFRPTYGVGH QPYRVWLSF E LLHAPATVC GPKKSTNLVK NKCVNFNFNG 540

LTGTGVLTES NKKF LPFQQF GRDIADTTDA VRDPQTLEI L DITPCSFGGV SVITPGTNTS 600

NQVAVLYQGV NCTEVPVAIH ADQLTPTWRV YSTGSNVFQT RAGCLIGAEY VNNSYECDIP 660

IGAGICASYQ TQTKSHRRAR SVASQSIIAY TMSLGAENSV AYSNNSIAI P TNFTISVTTE 720

I LPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV 780

KQIYKTPPIK YFGGFNFSQI LPDPSKPSKR SFI EDLLFNK VTLADAGFIK QYGDC LGDIA 840

ARDLICAQKF NGLTVLPPL L TDEMIAQYTS ALLAGTITSG WTFGAGAALQ IPFAMQMAYR 900

FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTASAL GKLQDWNHN AQALNTLVKQ 960

LSSKFGAISS VLNDILSRLD PPEAEVQIDR LITGRLQS LQ TYVTQQLIRA AEIRASANLA

1020

ATKMSECVLG QSKRVDFCGK GYHLMSFPQS APHGWFLHV TYVPAQEKNF TTAPAICHDG

1080

KAHFPREGVF VSNGTHWFVT QRNFYEPQII TTDNTFVSGN CDWIGIVNN TVYDPLQPEL

1140

DSFKE E LDKY FKNHTSPDVD LGDISGINAS WNIQKEIDR LNEVAKNLNE SLIDLQE LGK

1200

YEQYIKWPWY IWLGFIAGLI AIVMVTIMLC CMTSCCSC LK GCCSCGSCCK FDEDDSEPVL

1260

KGVKLHYT

1268

Sequence Number ( ID) : 101 Length : 3810

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1 . . 3810

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 accttcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgtcac agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaccgtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaagctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc 1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca 3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number ( ID) : 102

Length : 3810

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . . 3810

> mol_type, other DNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatctccgg caccaatggc accaagagat tcgacaaccc cgtgctgccc 240 ttcaacgacg gggtgtactt tgccagcacc gagaagtcca acatcatcag aggctggatc 300 ttcggcacca cactggacag caagacccag agcctgctga tcgtgaacaa cgccaccaac 360 gtggtcatca aagtgtgcga gttccagttc tgcaacgacc ccttcctgga cgtctactac 420 cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480 tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540 ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600 aagcacaccc ctatcaacct cggccgggat ctgcctcagg gcttctctgc tctggaaccc 660 ctggtggatc tgcccatcgg catcaacatc acccggtttc agacactgct ggccctgcac 720 agaagctacc tgacacctgg cgatagcagc agcggatgga cagctggtgc cgccgcttac 780 tatgtgggct acctgcagcc tagaaccttc ctgctgaagt acaacgagaa cggcaccatc 840 accgacgccg tggattgtgc tctggatcct ctgagcgaga caaagtgcac cctgaagtcc 900 ttcaccgtgg aaaagggcat ctaccagacc agcaacttcc gggtgcagcc caccgaatcc 960 atcgtgcggt tccccaatat caccaatctg tgccccttcg acgaggtgtt caatgccacc

1020 accttcgcct ctgtgtacgc ctggaaccgg aagcggatca gcaattgcgt ggccgactac

1080 tccgtgctgt acaacttcgc ccccttcttc gcattcaagt gctacggcgt gtcccctacc

1140 aagctgaacg acctgtgctt cacaaacgtg tacgccgaca gcttcgtgat ccggggaaac

1200 gaagtgtcac agattgcccc tggacagaca ggcaacatcg ccgactacaa ctacaagctg

1260 cccgacgact tcaccggctg tgtgattgcc tggaacagca acaagctgga ctccaccgtc

1320 ggcggcaact acaattacag gtaccggctg ttccggaagt ccaagctgaa gcccttcgag

1380 cgggacatct ccaccgagat ctatcaggcc ggcaacaagc cttgtaacgg cgtggcaggc

1440 gtgaactgct acttcccact gcagtcctac ggctttaggc ccacatacgg cgtgggccac

1500 cagccctaca gagtggtggt gctgagcttc gaactgctgc atgcccctgc cacagtgtgc

1560 ggccctaaga aaagcaccaa tctcgtgaag aacaaatgcg tgaacttcaa cttcaacggc

1620 ctgaccggca ccggcgtgct gacagagagc aacaagaagt tcctgccatt ccagcagttt

1680 ggccgggata tcgccgatac cacagacgcc gttagagatc cccagacact ggaaatcctg

1740 gacatcaccc cttgcagctt cggcggagtg tctgtgatca cccctggcac caacaccagc

1800 aatcaggtgg cagtgctgta ccagggcgtg aactgtaccg aagtgcccgt ggccattcac

1860 gccgatcagc tgacacctac atggcgggtg tactccaccg gcagcaatgt gtttcagacc

1920 agagccggct gtctgatcgg agccgagtac gtgaacaata gctacgagtg cgacatcccc

1980 atcggcgctg gaatctgcgc cagctaccag acacagacaa agagccaccg gagagccaga

2040 agcgtggcca gccagagcat cattgcctac acaatgtctc tgggcgccga gaacagcgtg

2100 gcctactcca acaactctat cgctatcccc accaacttca ccatcagcgt gaccacagag

2160 atcctgcctg tgtccatgac caagaccagc gtggactgca ccatgtacat ctgcggcgat

2220 tccaccgagt gctccaacct gctgctgcag tacggcagct tctgcaccca gctgaaaaga

2280 gccctgacag ggatcgccgt ggaacaggac aagaacaccc aagaggtgtt cgcccaagtg

2340 aagcagatct acaagacccc tcctatcaag tacttcggcg gcttcaattt cagccagatt

2400 ctgcccgatc ctagcaagcc cagcaagcgg agcttcatcg aggacctgct gttcaacaaa

2460 gtgacactgg ccgacgccgg cttcatcaag cagtatggcg attgtctggg cgacattgcc

2520 gccagggatc tgatttgcgc ccagaagttt aacggactga cagtgctgcc tcctctgctg

2580 accgatgaga tgatcgccca gtacacatct gccctgctgg ccggcacaat cacaagcggc

2640 tggacatttg gagcaggcgc cgctctgcag atcccctttg ctatgcagat ggcctaccgg

2700 ttcaacggca tcggagtgac ccagaatgtg ctgtacgaga accagaagct gatcgccaac

2760 cagttcaaca gcgccatcgg caagatccag gacagcctga gcagcacagc aagcgccctg

2820 ggaaagctgc aggacgtggt caaccacaat gcccaggcac tgaacaccct ggtcaagcag

2880 ctgtcctcca agttcggcgc catcagctct gtgctgaacg atatcctgag cagactggac

2940 cctcctgagg ccgaggtgca gatcgacaga ctgatcacag gcagactgca gagcctccag

3000 acatacgtga cccagcagct gatcagagcc gccgagatta gagcctctgc caatctggcc

3060 gccaccaaga tgtctgagtg tgtgctgggc cagagcaaga gagtggactt ttgcggcaag

3120 ggctaccacc tgatgagctt ccctcagtct gcccctcacg gcgtggtgtt tctgcacgtg

3180 acatatgtgc ccgctcaaga gaagaatttc accaccgctc cagccatctg ccacgacggc

3240 aaagcccact ttcctagaga aggcgtgttc gtgtccaacg gcacccattg gttcgtgaca

3300 cagcggaact tctacgagcc ccagatcatc accaccgaca acaccttcgt gtctggcaac

3360 tgcgacgtcg tgatcggcat tgtgaacaat accgtgtacg accctctgca gcccgagctg

3420 gacagcttca aagaggaact ggacaagtac tttaagaacc acacaagccc cgacgtggac

3480 ctgggcgata tcagcggaat caatgccagc gtcgtgaaca tccagaaaga gatcgaccgg

3540 ctgaacgagg tggccaagaa tctgaacgag agcctgatcg acctgcaaga actggggaag

3600 tacgagcagt acatcaagtg gccctggtac atctggctgg gctttatcgc cggactgatt

3660 gccatcgtga tggtcacaat catgctgtgt tgcatgacca gctgctgtag ctgcctgaag

3720 ggctgttgta gctgtggcag ctgctgcaag ttcgacgagg acgattctga gcccgtgctg

3780 aagggcgtga aactgcacta cacatgatga

3810

Sequence Number (ID) : 103

Length : 4267

Molecule Type : RNA

Features Location/Qualif iers :

- source, 1. .4267

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatctc cggcaccaat ggcaccaaga gattcgacaa ccccgtgctg cccttcaacg 300 acggggtgta ctttgccagc accgagaagt ccaacatcat cagaggctgg atcttcggca 360 ccacactgga cagcaagacc cagagcctgc tgatcgtgaa caacgccacc aacgtggtca 420 tcaaagtgtg cgagttccag ttctgcaacg accccttcct ggacgtctac taccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcaa cctcggccgg gatctgcctc agggcttctc tgctctggaa cccctggtgg 720 atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg cacagaagct 780 acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct tactatgtgg 840 gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc atcaccgacg 900 ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag tccttcaccg 960 tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa tccatcgtgc

1020 ggttccccaa tatcaccaat ctgtgcccct tcgacgaggt gttcaatgcc accaccttcg

1080 cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac tactccgtgc

1140 tgtacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct accaagctga

1200 acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga aacgaagtgt

1260 cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag ctgcccgacg

1320 acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccacc gtcggcggca

1380 actacaatta caggtaccgg ctgttccgga agtccaagct gaagcccttc gagcgggaca

1440 tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca ggcgtgaact

1500 gctacttccc actgcagtcc tacggcttta ggcccacata cggcgtgggc caccagccct

1560 acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg tgcggcccta

1620 agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac ggcctgaccg

1680 gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag tttggccggg

1740 atatcgccga taccacagac gccgttagag atccccagac actggaaatc ctggacatca

1800 ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc agcaatcagg

1860 tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt cacgccgatc

1920 agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag accagagccg

1980 gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc cccatcggcg 2040 ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc agaagcgtgg

2100 ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc gtggcctact

2160 ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca gagatcctgc

2220 ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc gattccaccg

2280 agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa agagccctga

2340 cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa gtgaagcaga

2400 tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag attctgcccg

2460 atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac aaagtgacac

2520 tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt gccgccaggg

2580 atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg ctgaccgatg

2640 agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc ggctggacat

2700 ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac cggttcaacg

2760 gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc aaccagttca

2820 acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc ctgggaaagc

2880 tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag cagctgtcct

2940 ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg gaccctcctg

3000 aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc cagacatacg

3060 tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg gccgccacca

3120 agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc aagggctacc

3180 acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac gtgacatatg

3240 tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac ggcaaagccc

3300 actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg acacagcgga

3360 acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc aactgcgacg

3420 tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag ctggacagct

3480 tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg gacctgggcg 3540 atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac cggctgaacg

3600 aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg aagtacgagc

3660 agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg attgccatcg

3720 tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg aagggctgtt

3780 gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg ctgaagggcg

3840 tgaaactgca ctacacatga tgactcgagc tggtactgca tgcacgcaat gctagctgcc

3900 cctttcccgt cctgggtacc ccgagtctcc cccgacctcg ggtcccaggt atgctcccac

3960 ctccacctgc cccactcacc acctctgcta gttccagaca cctcccaagc acgcagcaat

4020 gcagctcaaa acgcttagcc tagccacacc cccacgggaa acagcagtga ttaaccttta

4080 gcaataaacg aaagtttaac taagctatac taaccccagg gttggtcaat ttcgtgccag

4140 ccacaccctg gagctagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagc atatgactaa

4200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaa

4267

Sequence Number (ID) : 104

Length : 4267

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .4267

> mol_type, other DNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatctc cggcaccaat ggcaccaaga gattcgacaa ccccgtgctg cccttcaacg 300 acggggtgta ctttgccagc accgagaagt ccaacatcat cagaggctgg atcttcggca 360 ccacactgga cagcaagacc cagagcctgc tgatcgtgaa caacgccacc aacgtggtca 420 tcaaagtgtg cgagttccag ttctgcaacg accccttcct ggacgtctac taccacaaga 480 acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac aactgcacct 540 tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caagcagggc aacttcaaga 600 acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac agcaagcaca 660 cccctatcaa cctcggccgg gatctgcctc agggcttctc tgctctggaa cccctggtgg 720 atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg cacagaagct 780 acctgacacc tggcgatagc agcagcggat ggacagctgg tgccgccgct tactatgtgg 840 gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc atcaccgacg 900 ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag tccttcaccg 960 tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa tccatcgtgc

1020 ggttccccaa tatcaccaat ctgtgcccct tcgacgaggt gttcaatgcc accaccttcg

1080 cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac tactccgtgc

1140 tgtacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct accaagctga

1200 acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga aacgaagtgt

1260 cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag ctgcccgacg

1320 acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccacc gtcggcggca

1380 actacaatta caggtaccgg ctgttccgga agtccaagct gaagcccttc gagcgggaca

1440 tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca ggcgtgaact

1500 gctacttccc actgcagtcc tacggcttta ggcccacata cggcgtgggc caccagccct

1560 acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg tgcggcccta

1620 agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac ggcctgaccg

1680 gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag tttggccggg

1740 atatcgccga taccacagac gccgttagag atccccagac actggaaatc ctggacatca

1800 ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc agcaatcagg

1860 tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt cacgccgatc

1920 agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag accagagccg

1980 gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc cccatcggcg

2040 ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc agaagcgtgg

2100 ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc gtggcctact

2160 ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca gagatcctgc

2220 ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc gattccaccg

2280 agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa agagccctga

2340 cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa gtgaagcaga

2400 tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag attctgcccg

2460 atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac aaagtgacac

2520 tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt gccgccaggg

2580 atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg ctgaccgatg

2640 agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc ggctggacat

2700 ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac cggttcaacg

2760 gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc aaccagttca

2820 acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc ctgggaaagc

2880 tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag cagctgtcct

2940 ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg gaccctcctg

3000 aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc cagacatacg

3060 tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg gccgccacca

3120 agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc aagggctacc

3180 acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac gtgacatatg

3240 tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac ggcaaagccc

3300 actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg acacagcgga

3360 acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc aactgcgacg

3420 tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag ctggacagct

3480 tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg gacctgggcg

3540 atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac cggctgaacg

3600 aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg aagtacgagc

3660 agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg attgccatcg

3720 tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg aagggctgtt

3780 gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg ctgaagggcg

3840 tgaaactgca ctacacatga tgactcgagc tggtactgca tgcacgcaat gctagctgcc

3900 cctttcccgt cctgggtacc ccgagtctcc cccgacctcg ggtcccaggt atgctcccac

3960 ctccacctgc cccactcacc acctctgcta gttccagaca cctcccaagc acgcagcaat

4020 gcagctcaaa acgcttagcc tagccacacc cccacgggaa acagcagtga ttaaccttta

4080 gcaataaacg aaagtttaac taagctatac taaccccagg gttggtcaat ttcgtgccag

4140 ccacaccctg gagctagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagc atatgactaa

4200 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaa

4267

Sequence Number (ID) : 105

Length : 27

Molecule Type : AA

Features Location/Qualifiers :

- source, 1. .27

> mol_type, protein

> organism, synthetic construct

Residues :

MGGAAARLGA VILFWIVGL HGVRSKY 27

Sequence Number (ID) : 106

Length : 25

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 25

> mol_type, protein

> organism, synthetic construct

Residues :

MGRLTSGVGT AALLWAVGL RVVCA 25

Sequence Number (ID) : 107

Length : 28

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 28

> mol_type, protein

> organism, synthetic construct

Residues :

MGRLTSGVGT AALLWAVGL RVVCAKYA 28

Sequence Number (ID) : 108

Length : 19

Molecule Type : AA

Features Location/Qualifiers :

- source, 1. .19 > mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLT 19

Sequence Number (ID): 109

Length: 21

Molecule Type: AA

Features Location/Qualifiers :

- source, 1..21

> mol_type, protein

> organism, synthetic construct Residues :

MDWIWRILFL VGAATGAHSQ M 21

Sequence Number (ID): 110

Length: 20

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..20

> mol_type, protein

> organism, synthetic construct Residues :

METPAQLLFL LLLWLPDTTG 20

Sequence Number (ID): 111

Length: 18

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..18

> mol_type, protein

> organism, synthetic construct Residues :

MDWTWILFLV AAATRVHS 18

Sequence Number (ID): 112

Length: 24

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..24

> mol_type, protein

> organism, synthetic construct Residues :

MLGSNSGQRV VFTILLLLVA PAYS 24

Sequence Number (ID): 113

Length: 17

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..17 > mol_type, protein

> organism, synthetic construct

Residues :

MKCLLYLAFL FIGVNCA 17

Sequence Number (ID) : 114

Length : 18

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 18

> mol_type, protein

> organism, synthetic construct

Residues :

MDWTWILFLV AAATRVHS 18

Sequence Number (ID) : 115

Length : 19

Molecule Type : AA

Features Location/Qualifiers :

- source, 1. .19

> mol_type, protein

> organism, synthetic construct

Residues :

ETPAQLLFLL LLWLPDTTG 19

Sequence Number (ID) : 116

Length : 24

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 24

> mol_type, protein

> organism, synthetic construct

Residues :

MLGSNSGQRV VFTILLLLVA PAYS 24

Sequence Number (ID) : 117

Length : 17

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 17

> mol_type, protein

> organism, synthetic construct

Residues :

MKCLLYLAFL FIGVNCA 17

Sequence Number (ID) : 118

Length : 15

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 15 > mol_type, protein

> organism, synthetic construct

Residues : MWLVSLAIVT AC AGA 15

Sequence Number (ID) : 119 Length : 15

Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . . 15

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQC 15

Sequence Number (ID) : 120

Length : 81

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .81

> mol_type, other DNA

> organism, synthetic construct Residues : atgggggggg ctgccgccag gttgggggcc gtgattttgt ttgtcgtcat agtgggcctc 60 catggggtcc gcagcaaata t 81

Sequence Number (ID) : 121

Length : 81

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .81

> mol_type, other DNA

> organism, synthetic construct Residues : atgggaggag ccgccgccag actgggagcc gtgatcctgt tcgtggtgat cgtgggactg 60 catggagtga gaagcaagta c 81

Sequence Number (ID) : 122

Length : 57

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . . 57

> mol_type, other DNA

> organism, synthetic construct Residues : atgtttgtgt ttcttgtgct gctgcctctt gtgtcttctc agtgtgtgaa tttgaca 57

Sequence Number (ID) : 123 Length : 63 Molecule Type : DNA Features Location/Qualifiers:

- source, 1..63

> mol type, other DNA

> organism, synthetic construct

Residues : atggattgga tttggagaat cctgttcctc gtgggagccg ctacaggagc ccactcccag 60 atg 63

Sequence Number (ID): 124

Length: 5

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..5

> mol_type, protein

> organism, synthetic construct

Residues :

YLYRL 5

Sequence Number (ID): 125

Length: 5

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..5

> mol_type, protein

> organism, synthetic construct

Residues :

YRYRL 5

Sequence Number (ID): 126

Length: 5

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..5

> mol_type, protein

> organism, synthetic construct

Residues :

AGSTP 5

Sequence Number (ID): 127

Length: 5

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..5

> mol_type, protein

> organism, synthetic construct

Residues :

AGSKP 5

Sequence Number (ID): 128 Length: 5 Molecule Type: AA

Features Location/Qualifiers:

- source, 1..5

> mol_type, protein

> organism, synthetic construct Residues :

AGNKP 5

Sequence Number (ID): 129

Length: 250

Molecule Type: AA

Features Location/Qualifiers:

- source, 1. .250

> mol_type, protein

> organism, synthetic construct Residues :

CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN 60

CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD 120

YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC 180

NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV WLSFELLHA PATVCGPKKS TNLVKNKCVN 240

FNFNGLTGTG 250

Sequence Number (ID): 130

Length: 250

Molecule Type: AA

Features Location/Qualifiers:

- source, 1. .250

> mol_type, protein

> organism, synthetic construct Residues :

CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN 60

CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD 120

YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC 180

NGVEGFNCYF PLQSYGFQPT YGVGYQPYRV WLSFELLHA PATVCGPKKS TNLVKNKCVN 240

FNFNGLTGTG 250

Sequence Number (ID): 131

Length: 250

Molecule Type: AA

Features Location/Qualifiers:

- source, 1. .250

> mol_type, protein

> organism, synthetic construct Residues :

CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN 60

CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD 120

YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YRYRLFRKSN LKPFERDIST EIYQAGSKPC 180

NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV WLSFELLHA PATVCGPKKS TNLVKNKCVN 240

FNFNGLTGTG 250 Sequence Number (ID): 132 Length: 250 Molecule Type: AA Features Location/Qualifiers:

- source, 1..250

> mol_type, protein

> organism, synthetic construct Residues :

CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFDE VFNATRFASV YAWNRKRISN 60

CVADYSVLYN LAPFFTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGNIAD 120

YNYKLPDDFT GCVIAWNSNK LDSKVSGNYN YLYRLFRKSN LKPFERDIST EIYQAGNKPC 180

NGVAGFNCYF PLRSYSFRPT YGVGHQPYRV WLSFELLHA PATVCGPKKS TNLVKNKCVN 240

FNFNGLKGTG 250

Sequence Number (ID): 133 Length: 250

Molecule Type: AA Features Location/Qualifiers:

- source, 1. .250

> mol type, protein

> organism, synthetic construct Residues :

CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFDE VFNATRFASV YAWNRKRISN 60

CVADYSVLYN FAPFFAFKCY GVSPTKLNDL CFTNVYADSF VIRGNEVSQI APGQTGNIAD 120

YNYKLPDDFT GCVIAWNSNK LDSKVGGNYN YRYRLFRKSN LKPFERDIST EIYQAGNKPC 180

NGVAGVNCYF PLQSYGFRPT YGVGHQPYRV WLSFELLHA PATVCGPKKS TNLVKNKCVN 240

FNFNGLTGTG 250

Sequence Number (ID): 134

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

GSPGSGSGS

Sequence Number (ID): 135

Length: 6

Molecule Type: AA

Features Location/Qualifiers:

- source, 1. .6

> mol_type, protein

> organism, synthetic construct

Residues :

GSGSGS 6

Sequence Number (ID): 136 Length: 4 Molecule Type: AA

Features Location/Qualifiers:

- source, 1..4

> mol_type, protein

> organism, synthetic construct Residues :

RRAR 4

Sequence Number (ID): 137

Length: 12

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..12

> mol_type, protein

> organism, synthetic construct Residues :

CGGAGAGCCA GA 12

Sequence Number (ID): 138

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

YLQPRTFLL 9

Sequence Number (ID): 139

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

RLQSLQTYV 9

Sequence Number (ID): 140

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct Residues :

QYIKWPWYI 9

Sequence Number (ID): 141

Length: 9 Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

NYNYLYRLF 9

Sequence Number (ID): 142

Length: 10

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..10

> mol_type, protein

> organism, synthetic construct

Residues :

KWPWYIWLGF 10

Sequence Number (ID): 143

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

QPTESIVRF 9

Sequence Number (ID): 144

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

IPFAMQMAY 9

Sequence Number (ID): 145

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

LPFNDGVYF 9

Sequence Number (ID): 146

Length: 9 Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

GVYFASTEK 9

Sequence Number (ID): 147

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

CVADYSVLY 9

Sequence Number (ID): 148

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

FQPTNGVGY 9

Sequence Number (ID): 149

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

GTHWFVTQR 9

Sequence Number (ID): 150

Length: 9

Molecule Type: AA

Features Location/Qualifiers:

- source, 1..9

> mol_type, protein

> organism, synthetic construct

Residues :

VYDPLQPEL 9

Sequence Number (ID): 151

Length: 9 Molecule Type : AA

Features Location/Qualifiers :

- source, 1 . .9

> mol_type, protein

> organism, synthetic construct Residues :

KCYGVSPTK

Sequence Number (ID) : 152

Length : 3817

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . . 3817

> mol_type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cttcaccacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgcc 240 aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300 atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360 aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420 ctgggcgtct actaccacaa gaacaacaag agctggatgg aaagcgagtt ccgggtgtac 480 agcagcgcca acaactgcac cttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540 ggcaagcagg gcaacttcaa gaacctgcgc gagttcgtgt ttaagaacat cgacggctac 600 ttcaagatct acagcaagca cacccctatc aacctcgtgc ggggcctgcc tcagggcttc 660 tctgctctgg aacccctggt ggatctgccc atcggcatca acatcacccg gtttcagaca 720 ctgcacatca gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcggcga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa ctccgccagc ttcagcacct tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggagatgaag tgcggcagat tgcccctgga cagacaggca acatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa cctggactcc

1320 aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca gcaccccttg taacggcgtg

1440 aagggcttca actgctactt cccactgcag tcctacggct ttcagcccac atacggcgtg

1500 ggctatcagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagcacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaacag ccctcggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgtcgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aatagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaaggact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cagaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaactt cggcgccatc agctctgtgc tgaacgatat cctgagcaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatgac

3817

Sequence Number (ID) : 153

Length : 4274

Molecule Type : DNA Features Location/Qualifiers :

- source, 1. .4274

> mol type, other DNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacttcacc accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgccatccac gtgtccggca ccaatggcac caagagattc gccaaccccg 300 tgctgccctt caacgacggg gtgtactttg ccagcaccga gaagtccaac atcatcagag 360 gctggatctt cggcaccaca ctggacagca agacccagag cctgctgatc gtgaacaacg 420 ccaccaacgt ggtcatcaaa gtgtgcgagt tccagttctg caacgacccc ttcctgggcg 480 tctactacca caagaacaac aagagctgga tggaaagcga gttccgggtg tacagcagcg 540 ccaacaactg caccttcgag tacgtgtccc agcctttcct gatggacctg gaaggcaagc 600 agggcaactt caagaacctg cgcgagttcg tgtttaagaa catcgacggc tacttcaaga 660 tctacagcaa gcacacccct atcaacctcg tgcggggcct gcctcagggc ttctctgctc 720 tggaacccct ggtggatctg cccatcggca tcaacatcac ccggtttcag acactgcaca 780 tcagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggagatg

1260 aagtgcggca gattgcccct ggacagacag gcaacatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac tccaaagtcg

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcagcacccc ttgtaacggc gtgaagggct

1500 tcaactgcta cttcccactg cagtcctacg gctttcagcc cacatacggc gtgggctatc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa cagccctcgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgtcgag aacagcgtgg

2160 cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaatagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga 2400 agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccagaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa cttcggcgcc atcagctctg tgctgaacga tatcctgagc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt

3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgac tcgagctggt actgcatgca cgcaatgcta 3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa

4274

Sequence Number (ID) : 154 Length : 3816

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . . 3816

> mol_type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgc catctccggc accaatggca ccaagagatt cgacaacccc 240 gtgctgccct tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga 300 ggctggatct tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac 360 gccaccaacg tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctgggc 420 gtctaccaca agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc 480 aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540 ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600 tacagcaagc acacccctat caacctcgtg cgggatctgc ctcagggctt ctctgctctg 660 gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720 ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780 gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840 accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900 aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960 gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcggcga ggtgttcaat

1020 gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc

1080 gactactccg tgctgtacaa ctccgccagc ttcagcacct tcaagtgcta cggcgtgtcc

1140 cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg

1200 ggagatgaag tgcggcagat tgcccctgga cagacaggca agatcgccga ctacaactac

1260 aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa cctggactcc

1320 aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc

1380 ttcgagcggg acatctccac cgagatctat caggccggca gcaccccttg taacggcgtg

1440 gaaggcttca actgctactt cccactgcag tcctacggct ttcagcccac atacggcgtg

1500 ggctatcagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca

1560 gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc

1620 aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag

1680 cagtttggcc gggatatcga cgataccaca gacgccgtta gagatcccca gacactggaa

1740 atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac

1800 accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc

1860 attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt

1920 cagaccagag ccggctgtct gatcggagcc gagcacgtga acaatagcta cgagtgcgac

1980 atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaacag ccaccggaga

2040 gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac

2100 agcgtggcct actccaacaa ctctatcgct atccccatca acttcaccat cagcgtgacc

2160 acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc

2220 ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg

2280 aatagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc

2340 caagtgaagc agatctacaa gacccctcct atcaaggact tcggcggctt caatttcagc

2400 cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc

2460 aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac

2520 attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct

2580 ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca

2640 agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc

2700 taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc

2760 gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc

2820 gccctgggaa agctgcagga cgtggtcaac cagaatgccc aggcactgaa caccctggtc

2880 aagcagctgt cctccaactt cggcgccatc agctctgtgc tgaacgatat cctggccaga

2940 ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc

3000 ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat

3060 ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc

3120 ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg

3180 cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac

3240 gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc

3300 gtgacacagc ggaacttcta cgagccccag atcatcacca cccacaacac cttcgtgtct

3360 ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc

3420 gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac

3480 gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc

3540 gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg

3600 gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga

3660 ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc

3720 ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc

3780 gtgctgaagg gcgtgaaact gcactacaca tgatga

3816

Sequence Number (ID) : 155

Length : 4274

Molecule Type : DNA

Features Location/Qualif iers :

- source, 1. .4274

> mol_type, other DNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgacc accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgccatctcc ggcaccaatg gcaccaagag attcgacaac cccgtgctgc 300 ccttcaacga cggggtgtac tttgccagca ccgagaagtc caacatcatc agaggctgga 360 tcttcggcac cacactggac agcaagaccc agagcctgct gatcgtgaac aacgccacca 420 acgtggtcat caaagtgtgc gagttccagt tctgcaacga ccccttcctg ggcgtctacc 480 acaagaacaa caagagctgg atggaaagcg agttccgggt gtacagcagc gccaacaact 540 gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag cagggcaact 600 tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag atctacagca 660 agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct ctggaacccc 720 tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg gccctgcaca 780 gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc gccgcttact 840 atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac ggcaccatca 900 ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc ctgaagtcct 960 tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc accgaatcca

1020 tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc aatgccacca

1080 gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg gccgactact

1140 ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg tcccctacca

1200 agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc cggggagatg

1260 aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac tacaagctgc

1320 ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac tccaaagtcg

1380 gcggcaacta caattacctg taccggctgt tccggaagtc caatctgaag cccttcgagc

1440 gggacatctc caccgagatc tatcaggccg gcagcacccc ttgtaacggc gtggaaggct

1500 tcaactgcta cttcccactg cagtcctacg gctttcagcc cacatacggc gtgggctatc

1560 agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc acagtgtgcg

1620 gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac ttcaacggcc

1680 tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc cagcagtttg

1740 gccgggatat cgacgatacc acagacgccg ttagagatcc ccagacactg gaaatcctgg

1800 acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc aacaccagca

1860 atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg gccattcacg

1920 ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg tttcagacca

1980 gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc gacatcccca

2040 tcggcgctgg aatctgcgcc agctaccaga cacagacaaa cagccaccgg agagccagaa

2100 gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag aacagcgtgg 2160 cctactccaa caactctatc gctatcccca tcaacttcac catcagcgtg accacagaga

2220 tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc tgcggcgatt

2280 ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag ctgaatagag

2340 ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc gcccaagtga

2400 agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc agccagattc

2460 tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg ttcaacaaag

2520 tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc gacattgccg

2580 ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct cctctgctga

2640 ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc acaagcggct

2700 ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg gcctaccggt

2760 tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg atcgccaacc

2820 agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca agcgccctgg

2880 gaaagctgca ggacgtggtc aaccagaatg cccaggcact gaacaccctg gtcaagcagc

2940 tgtcctccaa cttcggcgcc atcagctctg tgctgaacga tatcctggcc agactggacc

3000 ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag agcctccaga

3060 catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc aatctggccg

3120 ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt tgcggcaagg

3180 gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt ctgcacgtga

3240 catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc cacgacggca

3300 aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg ttcgtgacac

3360 agcggaactt ctacgagccc cagatcatca ccacccacaa caccttcgtg tctggcaact

3420 gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag cccgagctgg

3480 acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc gacgtggacc

3540 tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag atcgaccggc

3600 tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa ctggggaagt 3660 acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc ggactgattg

3720 ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc tgcctgaagg

3780 gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag cccgtgctga

3840 agggcgtgaa actgcactac acatgatgag atctgctggt actgcatgca cgcaatgcta

3900 gctgcccctt tcccgtcctg ggtaccccga gtctcccccg acctcgggtc ccaggtatgc

3960 tcccacctcc acctgcccca ctcaccacct ctgctagttc cagacacctc ccaagcacgc

4020 agcaatgcag ctcaaaacgc ttagcctagc cacaccccca cgggaaacag cagtgattaa

4080 cctttagcaa taaacgaaag tttaactaag ctatactaac cccagggttg gtcaatttcg

4140 tgccagccac accctggagc tagcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaagcatat

4200 gactaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaa

4274

Sequence Number (ID) : 156

Length : 3819

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1 . . 3819

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgagaacc 60 agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120 aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180 aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240 aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300 atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360 aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420 ctggacgtct actaccacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480 gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540 cagggcaact tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag 600 atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660 ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780 gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840 ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900 ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960 accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc

1020 aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg

1080 gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg

1140 tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc

1200 cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac

1260 tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac

1320 tccaaagtcg gcggcaacta caattacagg taccggctgt tccggaagtc caatctgaag

1380 cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgtaacggc

1440 gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc

1500 gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc

1560 acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac

1620 ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc

1680 cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg

1740 gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc

1800 aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg

1860 gccattcacg ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg

1920 tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc

1980 gacatcccca tcggcgctgg aatctgcgcc agctaccaga cacagacaaa cagcaggcgg

2040 agagccagaa gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag

2100 aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg

2160 accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc

2220 tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag

2280 ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc

2340 gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc

2400 agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg

2460 ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc

2520 gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct

2580 cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc

2640 acaagcggct ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg

2700 gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg

2760 atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca

2820 agcgccctgg gaaagctgca gaacgtggtc aaccagaatg cccaggcact gaacaccctg

2880 gtcaagcagc tgtcctccaa cttcggcgcc atcagctctg tgctgaacga tatcctgagc

2940 agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag

3000 agcctccaga catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc

3060 aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt

3120 tgcggcaagg gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt

3180 ctgcacgtga catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc

3240 cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg

3300 ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg

3360 tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag

3420 cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc

3480 gacgtggacc tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag

3540 atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa

3600 ctggggaagt acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc

3660 ggactgattg ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc

3720 tgcctgaagg gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag

3780 cccgtgctga agggcgtgaa actgcactac acatgatga

3819

Sequence Number (ID) : 157 Length : 4277

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1 . .4277 > mol_type, other RNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgaga accagaacac 120 agctgcctcc agcctacacc aacagcttta ccagaggcgt gtactacccc gacaaggtgt 180 tcagatccag cgtgctgcac tctacccagg acctgttcct gcctttcttc agcaacgtga 240 cctggttcca cgccatccac gtgtccggca ccaatggcac caagagattc gacaaccccg 300 tgctgccctt caacgacggg gtgtactttg ccagcaccga gaagtccaac atcatcagag 360 gctggatctt cggcaccaca ctggacagca agacccagag cctgctgatc gtgaacaacg 420 ccaccaacgt ggtcatcaaa gtgtgcgagt tccagttctg caacgacccc ttcctggacg 480 tctactacca caagaacaac aagagctgga tggaaagcgg cgtgtacagc agcgccaaca 540 actgcacctt cgagtacgtg tcccagcctt tcctgatgga cctggaaggc aagcagggca 600 acttcaagaa cctgcgcgag ttcgtgttta agaacatcga cggctacttc aagatctaca 660 gcaagcacac ccctatcaac ctcgtgcggg atctgcctca gggcttctct gctctggaac 720 ccctggtgga tctgcccatc ggcatcaaca tcacccggtt tcagacactg ctggccctgc 780 acagaagcta cctgacacct ggcgatagca gcagcggatg gacagctggt gccgccgctt 840 actatgtggg ctacctgcag cctagaacct tcctgctgaa gtacaacgag aacggcacca 900 tcaccgacgc cgtggattgt gctctggatc ctctgagcga gacaaagtgc accctgaagt 960 ccttcaccgt ggaaaagggc atctaccaga ccagcaactt ccgggtgcag cccaccgaat

1020 ccatcgtgcg gttccccaat atcaccaatc tgtgcccctt cggcgaggtg ttcaatgcca

1080 ccagattcgc ctctgtgtac gcctggaacc ggaagcggat cagcaattgc gtggccgact

1140 actccgtgct gtacaactcc gccagcttca gcaccttcaa gtgctacggc gtgtccccta

1200 ccaagctgaa cgacctgtgc ttcacaaacg tgtacgccga cagcttcgtg atccggggag

1260 atgaagtgcg gcagattgcc cctggacaga caggcaagat cgccgactac aactacaagc

1320 tgcccgacga cttcaccggc tgtgtgattg cctggaacag caacaacctg gactccaaag

1380 tcggcggcaa ctacaattac aggtaccggc tgttccggaa gtccaatctg aagcccttcg

1440 agcgggacat ctccaccgag atctatcagg ccggcagcaa gccttgtaac ggcgtggaag

1500 gcttcaactg ctacttccca ctgcagtcct acggctttca gcccacaaat ggcgtgggct

1560 atcagcccta cagagtggtg gtgctgagct tcgaactgct gcatgcccct gccacagtgt

1620 gcggccctaa gaaaagcacc aatctcgtga agaacaaatg cgtgaacttc aacttcaacg

1680 gcctgaccgg caccggcgtg ctgacagaga gcaacaagaa gttcctgcca ttccagcagt

1740 ttggccggga tatcgccgat accacagacg ccgttagaga tccccagaca ctggaaatcc

1800 tggacatcac cccttgcagc ttcggcggag tgtctgtgat cacccctggc accaacacca

1860 gcaatcaggt ggcagtgctg taccagggcg tgaactgtac cgaagtgccc gtggccattc 1920 acgccgatca gctgacacct acatggcggg tgtactccac cggcagcaat gtgtttcaga

1980 ccagagccgg ctgtctgatc ggagccgagc acgtgaacaa tagctacgag tgcgacatcc

2040 ccatcggcgc tggaatctgc gccagctacc agacacagac aaacagcagg cggagagcca

2100 gaagcgtggc cagccagagc atcattgcct acacaatgtc tctgggcgcc gagaacagcg

2160 tggcctactc caacaactct atcgctatcc ccaccaactt caccatcagc gtgaccacag

2220 agatcctgcc tgtgtccatg accaagacca gcgtggactg caccatgtac atctgcggcg

2280 attccaccga gtgctccaac ctgctgctgc agtacggcag cttctgcacc cagctgaata

2340 gagccctgac agggatcgcc gtggaacagg acaagaacac ccaagaggtg ttcgcccaag

2400 tgaagcagat ctacaagacc cctcctatca aggacttcgg cggcttcaat ttcagccaga

2460 ttctgcccga tcctagcaag cccagcaagc ggagcttcat cgaggacctg ctgttcaaca

2520 aagtgacact ggccgacgcc ggcttcatca agcagtatgg cgattgtctg ggcgacattg

2580 ccgccaggga tctgatttgc gcccagaagt ttaacggact gacagtgctg cctcctctgc

2640 tgaccgatga gatgatcgcc cagtacacat ctgccctgct ggccggcaca atcacaagcg

2700 gctggacatt tggagcaggc gccgctctgc agatcccctt tgctatgcag atggcctacc

2760 ggttcaacgg catcggagtg acccagaatg tgctgtacga gaaccagaag ctgatcgcca

2820 accagttcaa cagcgccatc ggcaagatcc aggacagcct gagcagcaca gcaagcgccc

2880 tgggaaagct gcagaacgtg gtcaaccaga atgcccaggc actgaacacc ctggtcaagc

2940 agctgtcctc caacttcggc gccatcagct ctgtgctgaa cgatatcctg agcagactgg

3000 accctcctga ggccgaggtg cagatcgaca gactgatcac aggcagactg cagagcctcc

3060 agacatacgt gacccagcag ctgatcagag ccgccgagat tagagcctct gccaatctgg

3120 ccgccaccaa gatgtctgag tgtgtgctgg gccagagcaa gagagtggac ttttgcggca

3180 agggctacca cctgatgagc ttccctcagt ctgcccctca cggcgtggtg tttctgcacg

3240 tgacatatgt gcccgctcaa gagaagaatt tcaccaccgc tccagccatc tgccacgacg

3300 gcaaagccca ctttcctaga gaaggcgtgt tcgtgtccaa cggcacccat tggttcgtga

3360 cacagcggaa cttctacgag ccccagatca tcaccaccga caacaccttc gtgtctggca 3420 actgcgacgt cgtgatcggc attgtgaaca ataccgtgta cgaccctctg cagcccgagc

3480 tggacagctt caaagaggaa ctggacaagt actttaagaa ccacacaagc cc cgacgtgg

3540 ac ctgggcga tatcagcgga atcaatgcca gcgtcgtgaa catccagaaa gagatcgacc

3600 ggctgaacga ggtggc caag aatctgaacg agagcctgat cgacctgcaa gaactgggga

3660 agtacgagca gtacatcaag tggccctggt acatctggct gggctttatc gc cggactga

3720 ttgccatcgt gatggtcaca atcatgctgt gttgcatgac cagctgctgt agctgcctga

3780 agggctgttg tagctgtggc agctgctgca agttcgacga ggacgattct gagcccgtgc

3840 tgaagggcgt gaaactgcac tacacatgat gatttcacct ggtactgcat gcacgcaatg

3900 ctagctgcc c ctttcccgtc ctgggtaccc cgagtctcc c ccgacctcgg gtcccaggta

3960 tgctc ccac c tccacctgc c ccactcacca cctctgctag ttccagacac ctcccaagca

4020 cgcagcaatg cagctcaaaa cgcttagcct agccacacc c ccacgggaaa cagcagtgat

4080 taacctttag caataaacga aagtttaact aagctatact aaccccaggg ttggtcaatt

4140 tcgtgccagc cacaccctgg agctagcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaagca

4200 tatgactaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa aaaaaaa

4277

Sequence Number ( ID) : 158

Length : 1269

Molec ule Type : AA

Featu res Location/Qualif iers :

- sou rce, 1 . . 1269

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD L F LPF FSNVT 60 WFHAIHVSGT NGTKRFDNPA LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA 120 TNWIKVCE F QFCNDPF LDV YQKNNKSWME SE FRVYSSAN NCTF EYVSQP F LMDL EGKEG 180 NFKNLREFVF KNIDGYFKIY SKHTPINLER DLPQGFSAL E PLVDLPIGIN ITRFQTLLAL 240 HRSYLTPVDS SSGWTAGAAA YYVGYLQPRT F LLKYNENGT ITDAVDCALD PLSETKCTLK 300 SFTVEKGIYQ TSNF RVQPTE SIVRFPNITN LCPFHEVFNA TTFASVYAWN RKRISNCVAD 360 YSVIYNFAPF FAFKCYGVSP TKLNDLCFTN VYADSFVI RG NEVSQIAPGQ TGNIADYNYK 420 LPDDFTGCVI AWNSNKLDSK PSGNYNYLYR LFRKSKLKPF ERDISTEIYQ AGNKPCNGVA 480 GPNCYSPLQS YGFRPTYGVG HQPYRWVLS FE LLHAPATV CGPKKSTNLV KNKCVNFNFN 540

GLTGTGVLTE SNKKFLPFQQ FGRDIADTTD AVRDPQTL EI LDITPCSFGG VSVITPGTNT 600 SNQVAVLYQG VNCTEVPVAI HADQLTPTWR VYSTGSNVFQ TRAGCLIGAE YVNNSYECDI 660 PIGAGICASY QTQTKSHRRA RSVASQSIIA YTMSLGAENS VAYSNNSIAI PTNFTISVTT 720 EI LPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ 780 VKQIYKTPPI KYFGGFNFSQ I LPDPSKPSK RS FIEDLLFN KVTLADAGFI KQYGDCLGDI 840 AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAAL QI PFAMQMAY 900 RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QDSLSSTASA LGKLQDWNH NAQALNTLVK 960 QLSSKFGAIS SVLNDI LSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL

1020

AATKMS ECVL GQSKRVDFCG KGYHLMSFPQ SAPHGWF LH VTYVPAQEKN FTTAPAICHD

1080

GKAHF PREGV FVSNGTHWFV TQRNFYEPQI ITTDNTFVSG NCDWIGIVN NTVYDPLQPE

1140

LDSFKE ELDK YFKNHTSPDV DLGDISGINA SVVNIQKEID RLNEVAKNLN ES LIDLQE LG

1200

KYEQYIKWPW YIWLGFIAGL IAIVMVTIML CCMTSCCSC L KGCCSCGSCC KFDEDDSEPV

1260

LKGVKLHYT

1269

Sequence Number ( ID) : 159

Length : 3813

Molec ule Type : RNA

Featu res Location/Qualifiers :

- source, 1 . . 3813

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgc ctctg gtgtc cagc c agtgtgtgaa c ctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatc cagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg c catccacgt gtccggcacc aatggcacca agagattcga caacc ccgcc 240 ctgcc cttca acgacggggt gtactttgcc agcac cgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagc c tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt c ctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcac ct tcgagtacgt gtcc cagc ct ttcctgatgg acctggaagg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg 720 cacagaagct acctgacacc tgtggatagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctac cag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccc caa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcc cct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga 1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac 2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number (ID) : 160

Length : 3813

Molecule Type : DNA

Features Location/Qualif iers :

- source, 1 . . 3813

> mol_type, other DNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcacct tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg 720 cacagaagct acctgacacc tgtggatagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number (ID) : 161

Length : 4270

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1 . .4270

> mol_type, other RNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctgtggat agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg 1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt 2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270

Sequence Number (ID) : 162 Length : 4270 Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . .4270

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctgtggat agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270

Sequence Number (ID) : 163

Length : 1269

Molecule Type : AA

Features Location/Qualif iers :

- source, 1 . . 1269

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAIHVSGT NGTKRFDNPA LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA 120

TNWIKVCEF QFCNDPFLDV YQKNNKSWME SEFRVYSSAN NCTFEYVSQP FLMDLVGKEG 180

NFKNLREFVF KNIDGYFKIY SKHTPINLER DLPQGFSALE PLVDLPIGIN ITRFQTLLAL 240

HRSYLTPVDS SSGWTAGAAA YYVGYLQPRT FLLKYNENGT ITDAVDCALD PLSETKCTLK 300

SFTVEKGIYQ TSNFRVQPTE SIVRFPNITN LCPFHEVFNA TTFASVYAWN RKRISNCVAD 360

YSVIYNFAPF FAFKCYGVSP TKLNDLCFTN VYADSFVIRG NEVSQIAPGQ TGNIADYNYK 420 LPDDFTGCVI AWNSNKLDSK PSGNYNYLYR LF RKSKLKPF ERDISTEIYQ AGNRPCNGVA 480 GPNCYSPLQS YGFRPTYGVG HQPYRVWLS F E LLHAPATV CGPKKSTNLV KNKCVNFNFN 540 GLTGTGVLTE SNKKFLPFQQ FGRDIADTTD AVRDPQTLEI LDITPCSFGG VSVITPGTNT 600 SNQVAVLYQG VNCTEVPVAI HADQLTPTWR VYSTGSNVFQ TRAGCLIGAE YVNNSYECDI 660 PIGAGICASY QTQTKSHRRA RSVASQSIIA YTMSLGAENS VAYSNNSIAI PTNFTISVTT 720 EI LPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ 780 VKQIYKTPPI KYFGGFNFSQ I LPDPSKPSK RS FIEDLLFN KVTLADAGFI KQYGDCLGDI 840 AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAAL QI PFAMQMAY 900 RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QDSLSSTASA LGKLQDWNH NAQALNTLVK 960

QLSSKFGAIS SVLNDI LSRL DPPEAEVQID RLITGRLQS L QTYVTQQLI R AAEIRASANL

1020

AATKMSECVL GQSKRVDFCG KGYHLMSFPQ SAPHGWF LH VTYVPAQEKN FTTAPAICHD

1080

GKAHF PREGV FVSNGTHWFV TQRNFYEPQI ITTDNTFVSG NCDWIGIVN NTVYDPLQPE

1140

LDSFKE ELDK YFKNHTSPDV DLGDISGINA SVVNIQKEID RLNEVAKNLN ES LIDLQE LG

1200

KYEQYIKWPW YIWLGFIAGL IAIVMVTIML CCMTSCCSC L KGCCSCGSCC KFDEDDSEPV

1260

LKGVKLHYT

1269

Sequence Number ( ID) : 164

Length : 3813

Molec ule Type : RNA

Featu res Location/Qualif iers :

- sou rce, 1 . . 3813

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgc ctctg gtgtc cagc c agtgtgtgaa c ctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatc cagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg c catccacgt gtccggcacc aatggcacca agagattcga caacc ccgcc 240 ctgcc cttca acgacggggt gtactttgcc agcaccgaga agtc caacat catcagaggc 300 tggatcttcg gcac cacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcac ct tcgagtacgt gtcc cagc ct ttcctgatgg acctggtggg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggcc ctg 720 cacagaagct acctgacacc tgtggatagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttc ctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctac cag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccc caa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca ggccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number (ID) : 165

Length : 3813

Molecule Type : DNA

Features Location/Qualif iers :

- source, 1. .3813

> mol_type, other DNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcacct tcgagtacgt gtcccagcct ttcctgatgg acctggtggg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg 720 cacagaagct acctgacacc tgtggatagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca ggccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcccc tgccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc 1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg 3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number (ID) : 166

Length : 4270

Molecule Type : RNA Features Location/Qualifiers :

- source, 1 . .4270

> mol type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctggt gggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctgtggat agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaggccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270 Sequence Number (ID) : 167

Length : 4270

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . .4270

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctggt gggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctgtggat agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaggccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc 1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat 3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270

Sequence Number (ID) : 168

Length : 1269

Molecule Type : AA

Features Location/Qualif iers :

- source, 1 . . 1269

> mol_type, protein

> organism, synthetic construct

Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60

WFHAIHVSGT NGTKRFDNPA LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA 120

TNWIKVCEF QFCNDPFLDV YQKNNKSWME SEFRVYSSAN NCTFEYVSQP FLMDLEGKEG 180

NFKNLREFVF KNIDGYFKIY SKHTPINLER DLPQGFSALE PLVDLPIGIN ITRFQTLLAL 240 HRSYLTPGGS SSGWTAGAAA YYVGYLQPRT F L LKYNENGT ITDAVDCALD PLSETKCTLK 300 SFTVEKGIYQ TSNFRVQPTE SIVRFPNITN LCPFHEVFNA TTFASVYAWN RKRISNCVAD 360 YSVIYNFAPF FAFKCYGVSP TKLNDLCFTN VYADSFVIRG NEVSQIAPGQ TGNIADYNYK 420 LPDDFTGCVI AWNSNKLDSK PSGNYNYLYR LF RKSKLKPF ERDISTEIYQ AGNKPCNGVA 480 GPNCYSPLQS YGFRPTYGVG HQPYRVWLS F E LLHASATV CGPKKSTNLV KNKCVNFNFN 540 GLTGTGVLTE SNKKFLPFQQ FGRDIADTTD AVRDPQTLEI LDITPCSFGG VSVITPGTNT 600 SNQVAVLYQG VNCTEVPVAI HADQLTPTWR VYSTGSNVFQ TRAGCLIGAE YVNNSYECDI 660 PIGAGICASY QTQTKSHRRA RSVASQSIIA YTMSLGAENS VAYSNNSIAI PTNFTISVTT 720 EI LPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ 780 VKQIYKTPPI KYFGGFNFSQ I LPDPSKPSK RS FIEDLLFN KVTLADAGF I KQYGDCLGDI 840 AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAAL QI PFAMQMAY 900 RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QDSLSSTASA LGKLQDWNH NAQALNTLVK 960 QLSSKFGAIS SVLNDI LSRL DPPEAEVQID RLITGRLQS L QTYVTQQLI R AAEIRASANL

1020

AATKMSECVL GQSKRVDFCG KGYHLMSFPQ SAPHGWF LH VTYVPAQEKN FTTAPAICHD

1080

GKAHF PREGV FVSNGTHWFV TQRNFYEPQI ITTDNTFVSG NCDWIGIVN NTVYDPLQPE

1140

LDSFKE ELDK YFKNHTSPDV DLGDISGINA SWNIQKE ID RLNEVAKNLN ESLIDLQE LG

1200

KYEQYIKWPW YIWLGFIAGL IAIVMVTIML CCMTSCCSCL KGCCSCGSCC KFDEDDSE PV

1260

LKGVKLHYT

1269

Sequence Number ( ID) : 169

Length : 3813

Molec ule Type : RNA

Featu res Location/Qualif iers :

- sou rce, 1 . . 3813

> mol_type, other RNA

> organism, synthetic construct

Residues : atgttcgtgt tcctggtgct gctgc ctctg gtgtc cagc c agtgtgtgaa c ctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacc caggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg c catccacgt gtccggcacc aatggcac ca agagattcga caac cccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtc caacat catcagaggc 300 tggatcttcg gcac cacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt c ctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcac ct tcgagtacgt gtcc cagc ct ttcctgatgg acctggaagg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcc cat cggcatcaac atcacccggt ttcagacact gctggcc ctg 720 cacagaagct acctgacacc tggcggcagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg cacc ctgaag 900 tccttcaccg tggaaaaggg catctac cag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccc caa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc 1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcctc agccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt 2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number (ID) : 170

Length : 3813

Molecule Type : DNA

Features Location/Qualifiers : - source, 1. . 3813

> mol_type, other DNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcacct tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caaggagggc 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg 720 cacagaagct acctgacacc tggcggcagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcctc agccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number ( ID) : 171

Length : 4270

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1. .4270

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctggcggc agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag 1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ctcagccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca 2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4260 aaaaaaaaaa

4270

Sequence Number (ID) : 172

Length : 4270

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1. .4270

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag ggcaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctggcggc agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ctcagccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270

Sequence Number (ID) : 173

Length : 1269

Molecule Type : AA

Features Location/Qualif iers :

- source, 1. .1269

> mol_type, protein

> organism, synthetic construct Residues :

MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT 60 WFHAIHVSGT NGTKRFDNPA LPFNDGVYFA STEKSNIIRG WI FGTTLDSK TQSLLIVNNA 120 TNWIKVCE F QFCNDPF LDV YQKNNKSWME SE FRVYSSAN NCTF EYVSQP F LMDLEGKEV 180 NFKNLREFVF KNIDGYFKIY SKHTPINLER DLPQGFSALE PLVDLPIGIN ITRFQTLLAL 240 HRSYLTPGGS SSGWTAGAAA YYVGYLQPRT F L LKYNENGT ITDAVDCALD PLSETKCTLK 300 SFTVEKGIYQ TSNFRVQPTE SIVRFPNITN LCPFHEVFNA TTFASVYAWN RKRISNCVAD 360 YSVIYNFAPF FAFKCYGVSP TKLNDLCFTN VYADSFVIRG NEVSQIAPGQ TGNIADYNYK 420 LPDDFTGCVI AWNSNKLDSK PSGNYNYLYR LF RKSKLKPF ERDISTEIYQ AGNKPCNGVA 480 GPNCYSPLQS YGFRPTYGVG HQPYRWVLS F E LLHASATV CGPKKSTNLV KNKCVNFNFN 540 GLTGTGVLTE SNKKF LPFQQ FGRDIADTTD AVRDPQTLE I LDITPCSFGG VSVITPGTNT 600 SNQVAVLYQG VNCTEVPVAI HADQLTPTWR VYSTGSNVFQ TRAGCLIGAE YVNNSYECDI 660 PIGAGICASY QTQTKSHRRA RSVASQSIIA YTMSLGAENS VAYSNNSIAI PTNFTISVTT 720 EI LPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ 780 VKQIYKTPPI KYFGGFNFSQ I LPDPSKPSK RS FIEDLLFN KVTLADAGF I KQYGDCLGDI 840 AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAAL QI PFAMQMAY 900 RFNGIGVTQN VLYENQKLIA NQFNSAIGKI QDSLSSTASA LGKLQDWNH NAQALNTLVK 960 QLSSKFGAIS SVLNDI LSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL

1020

AATKMSECVL GQSKRVDFCG KGYHLMSF PQ SAPHGWF LH VTYVPAQEKN FTTAPAICHD

1080

GKAHF PREGV FVSNGTHWFV TQRNFYEPQI ITTDNTFVSG NCDWIGIVN NTVYDPLQPE

1140 LDSFKE ELDK YFKNHTSPDV DLGDISGINA SWNIQKE ID RLNEVAKNLN ESLIDLQE LG

1200

KYEQYIKWPW YIWLGFIAGL IAIVMVTIML CCMTSCCSCL KGCCSCGSCC KFDEDDSE PV

1260

LKGVKLHYT

1269

Sequence Number ( ID) : 174

Length : 3813

Molec ule Type : RNA

Featu res Location/Qualif iers :

- source, 1 . . 3813

> mol_type, other RNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacc caggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcac ca agagattcga caac cccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtc caacat catcagaggc 300 tggatcttcg gcac cacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgaccc ctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcacct tcgagtacgt gtcc cagcct ttcctgatgg acctggaagg caaggaggtg 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcc cat cggcatcaac atcacccggt ttcagacact gctggcc ctg 720 cacagaagct acctgacacc tggcggcagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttc ctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcctc agccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc

1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg

3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number (ID) : 175 Length : 3813

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . . 3813

> mol_type, other DNA

> organism, synthetic construct Residues : atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgatcacc 60 agaacacagt catacaccaa cagctttacc agaggcgtgt actaccccga caaggtgttc 120 agatccagcg tgctgcactc tacccaggac ctgttcctgc ctttcttcag caacgtgacc 180 tggttccacg ccatccacgt gtccggcacc aatggcacca agagattcga caaccccgcc 240 ctgcccttca acgacggggt gtactttgcc agcaccgaga agtccaacat catcagaggc 300 tggatcttcg gcaccacact ggacagcaag acccagagcc tgctgatcgt gaacaacgcc 360 accaacgtgg tcatcaaagt gtgcgagttc cagttctgca acgacccctt cctggacgtc 420 taccagaaga acaacaagag ctggatggaa agcgagttcc gggtgtacag cagcgccaac 480 aactgcacct tcgagtacgt gtcccagcct ttcctgatgg acctggaagg caaggaggtg 540 aacttcaaga acctgcgcga gttcgtgttt aagaacatcg acggctactt caagatctac 600 agcaagcaca cccctatcaa cctcgagcgg gatctgcctc agggcttctc tgctctggaa 660 cccctggtgg atctgcccat cggcatcaac atcacccggt ttcagacact gctggccctg 720 cacagaagct acctgacacc tggcggcagc agcagcggat ggacagctgg tgccgccgct 780 tactatgtgg gctacctgca gcctagaacc ttcctgctga agtacaacga gaacggcacc 840 atcaccgacg ccgtggattg tgctctggat cctctgagcg agacaaagtg caccctgaag 900 tccttcaccg tggaaaaggg catctaccag accagcaact tccgggtgca gcccaccgaa 960 tccatcgtgc ggttccccaa tatcaccaat ctgtgcccct tccacgaggt gttcaatgcc

1020 accaccttcg cctctgtgta cgcctggaac cggaagcgga tcagcaattg cgtggccgac

1080 tactccgtga tctacaactt cgcccccttc ttcgcattca agtgctacgg cgtgtcccct

1140 accaagctga acgacctgtg cttcacaaac gtgtacgccg acagcttcgt gatccgggga

1200 aacgaagtgt cacagattgc ccctggacag acaggcaaca tcgccgacta caactacaag

1260 ctgcccgacg acttcaccgg ctgtgtgatt gcctggaaca gcaacaagct ggactccaaa

1320 cccagcggca actacaatta cctgtaccgg ctgttccgga agtccaagct gaagcccttc

1380 gagcgggaca tctccaccga gatctatcag gccggcaaca agccttgtaa cggcgtggca

1440 ggccccaact gctacagccc actgcagtcc tacggcttta ggcccacata cggcgtgggc

1500 caccagccct acagagtggt ggtgctgagc ttcgaactgc tgcatgcctc agccacagtg

1560 tgcggcccta agaaaagcac caatctcgtg aagaacaaat gcgtgaactt caacttcaac

1620 ggcctgaccg gcaccggcgt gctgacagag agcaacaaga agttcctgcc attccagcag

1680 tttggccggg atatcgccga taccacagac gccgttagag atccccagac actggaaatc

1740 ctggacatca ccccttgcag cttcggcgga gtgtctgtga tcacccctgg caccaacacc 1800 agcaatcagg tggcagtgct gtaccagggc gtgaactgta ccgaagtgcc cgtggccatt

1860 cacgccgatc agctgacacc tacatggcgg gtgtactcca ccggcagcaa tgtgtttcag

1920 accagagccg gctgtctgat cggagccgag tacgtgaaca atagctacga gtgcgacatc

1980 cccatcggcg ctggaatctg cgccagctac cagacacaga caaagagcca ccggagagcc

2040 agaagcgtgg ccagccagag catcattgcc tacacaatgt ctctgggcgc cgagaacagc

2100 gtggcctact ccaacaactc tatcgctatc cccaccaact tcaccatcag cgtgaccaca

2160 gagatcctgc ctgtgtccat gaccaagacc agcgtggact gcaccatgta catctgcggc

2220 gattccaccg agtgctccaa cctgctgctg cagtacggca gcttctgcac ccagctgaaa

2280 agagccctga cagggatcgc cgtggaacag gacaagaaca cccaagaggt gttcgcccaa

2340 gtgaagcaga tctacaagac ccctcctatc aagtacttcg gcggcttcaa tttcagccag

2400 attctgcccg atcctagcaa gcccagcaag cggagcttca tcgaggacct gctgttcaac

2460 aaagtgacac tggccgacgc cggcttcatc aagcagtatg gcgattgtct gggcgacatt

2520 gccgccaggg atctgatttg cgcccagaag tttaacggac tgacagtgct gcctcctctg

2580 ctgaccgatg agatgatcgc ccagtacaca tctgccctgc tggccggcac aatcacaagc

2640 ggctggacat ttggagcagg cgccgctctg cagatcccct ttgctatgca gatggcctac

2700 cggttcaacg gcatcggagt gacccagaat gtgctgtacg agaaccagaa gctgatcgcc

2760 aaccagttca acagcgccat cggcaagatc caggacagcc tgagcagcac agcaagcgcc

2820 ctgggaaagc tgcaggacgt ggtcaaccac aatgcccagg cactgaacac cctggtcaag

2880 cagctgtcct ccaagttcgg cgccatcagc tctgtgctga acgatatcct gagcagactg

2940 gaccctcctg aggccgaggt gcagatcgac agactgatca caggcagact gcagagcctc

3000 cagacatacg tgacccagca gctgatcaga gccgccgaga ttagagcctc tgccaatctg

3060 gccgccacca agatgtctga gtgtgtgctg ggccagagca agagagtgga cttttgcggc

3120 aagggctacc acctgatgag cttccctcag tctgcccctc acggcgtggt gtttctgcac

3180 gtgacatatg tgcccgctca agagaagaat ttcaccaccg ctccagccat ctgccacgac

3240 ggcaaagccc actttcctag agaaggcgtg ttcgtgtcca acggcaccca ttggttcgtg 3300 acacagcgga acttctacga gccccagatc atcaccaccg acaacacctt cgtgtctggc

3360 aactgcgacg tcgtgatcgg cattgtgaac aataccgtgt acgaccctct gcagcccgag

3420 ctggacagct tcaaagagga actggacaag tactttaaga accacacaag ccccgacgtg

3480 gacctgggcg atatcagcgg aatcaatgcc agcgtcgtga acatccagaa agagatcgac

3540 cggctgaacg aggtggccaa gaatctgaac gagagcctga tcgacctgca agaactgggg

3600 aagtacgagc agtacatcaa gtggccctgg tacatctggc tgggctttat cgccggactg

3660 attgccatcg tgatggtcac aatcatgctg tgttgcatga ccagctgctg tagctgcctg

3720 aagggctgtt gtagctgtgg cagctgctgc aagttcgacg aggacgattc tgagcccgtg

3780 ctgaagggcg tgaaactgca ctacacatga tga

3813

Sequence Number ( ID) : 176

Length : 4270

Molecule Type : RNA

Features Location/Qualifiers :

- source, 1. .4270

> mol_type, other RNA

> organism, synthetic construct Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag gtgaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctggcggc agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc

1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ctcagccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat

3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270

Sequence Number (ID) : 177

Length : 4270

Molecule Type : DNA

Features Location/Qualifiers :

- source, 1 . .4270

> mol_type, other DNA

> organism, synthetic construct

Residues : agaataaact agtattcttc tggtccccac agactcagag agaacccgcc accatgttcg 60 tgttcctggt gctgctgcct ctggtgtcca gccagtgtgt gaacctgatc accagaacac 120 agtcatacac caacagcttt accagaggcg tgtactaccc cgacaaggtg ttcagatcca 180 gcgtgctgca ctctacccag gacctgttcc tgcctttctt cagcaacgtg acctggttcc 240 acgccatcca cgtgtccggc accaatggca ccaagagatt cgacaacccc gccctgccct 300 tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga ggctggatct 360 tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac gccaccaacg 420 tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac gtctaccaga 480 agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc aacaactgca 540 ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaaggag gtgaacttca 600 agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc tacagcaagc 660 acacccctat caacctcgag cgggatctgc ctcagggctt ctctgctctg gaacccctgg 720 tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc ctgcacagaa 780 gctacctgac acctggcggc agcagcagcg gatggacagc tggtgccgcc gcttactatg 840 tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc accatcaccg 900 acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg aagtccttca 960 ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc gaatccatcg

1020 tgcggttccc caatatcacc aatctgtgcc ccttccacga ggtgttcaat gccaccacct

1080 tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc gactactccg

1140 tgatctacaa cttcgccccc ttcttcgcat tcaagtgcta cggcgtgtcc cctaccaagc

1200 tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg ggaaacgaag

1260 tgtcacagat tgcccctgga cagacaggca acatcgccga ctacaactac aagctgcccg

1320 acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc aaacccagcg

1380 gcaactacaa ttacctgtac cggctgttcc ggaagtccaa gctgaagccc ttcgagcggg

1440 acatctccac cgagatctat caggccggca acaagccttg taacggcgtg gcaggcccca

1500 actgctacag cccactgcag tcctacggct ttaggcccac atacggcgtg ggccaccagc 1560 cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ctcagccaca gtgtgcggcc

1620 ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc aacggcctga

1680 ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag cagtttggcc

1740 gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa atcctggaca

1800 tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac accagcaatc

1860 aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc attcacgccg

1920 atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt cagaccagag

1980 ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac atccccatcg

2040 gcgctggaat ctgcgccagc taccagacac agacaaagag ccaccggaga gccagaagcg

2100 tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac agcgtggcct

2160 actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc acagagatcc

2220 tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc ggcgattcca

2280 ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg aaaagagccc

2340 tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc caagtgaagc

2400 agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc cagattctgc

2460 ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc aacaaagtga

2520 cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac attgccgcca

2580 gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct ctgctgaccg

2640 atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca agcggctgga

2700 catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc taccggttca

2760 acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc gccaaccagt

2820 tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc gccctgggaa

2880 agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc aagcagctgt

2940 cctccaagtt cggcgccatc agctctgtgc tgaacgatat cctgagcaga ctggaccctc

3000 ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc ctccagacat 3060 acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat ctggccgcca

3120 ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc ggcaagggct

3180 accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg cacgtgacat

3240 atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac gacggcaaag

3300 cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc gtgacacagc

3360 ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct ggcaactgcg

3420 acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc gagctggaca

3480 gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac gtggacctgg

3540 gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc gaccggctga

3600 acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg gggaagtacg

3660 agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga ctgattgcca

3720 tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc ctgaagggct

3780 gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc gtgctgaagg

3840 gcgtgaaact gcactacaca tgatgactcg agctggtact gcatgcacgc aatgctagct

3900 gcccctttcc cgtcctgggt accccgagtc tcccccgacc tcgggtccca ggtatgctcc

3960 cacctccacc tgccccactc accacctctg ctagttccag acacctccca agcacgcagc

4020 aatgcagctc aaaacgctta gcctagccac acccccacgg gaaacagcag tgattaacct

4080 ttagcaataa acgaaagttt aactaagcta tactaacccc agggttggtc aatttcgtgc

4140 cagccacacc ctggagctag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa agcatatgac

4200 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

4260 aaaaaaaaaa

4270 END

Claims

Claims

1. A ribonucleic acid (RNA) comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises:

(i) a receptor binding domain (RBD) of a coronavirus Spike (S) protein; and

(ii) an S2 domain of a coronavirus S protein or one or more fragments thereof; wherein the RBD and the S2 domain or the one or more fragments thereof are directly adjacent to one another or are connected via a non-endogenous sequence.

2. The RNA of claim 1, wherein the polypeptide comprises a stem helix and a fusion peptide of an S2 domain of a coronavirus S protein.

3. The RNA of claim 1 or 2, wherein the RBD comprises amino acids 327 to 528 of SEQ ID NO: 1, 330 to 528 of SEQ ID NO: 1, amino acids 327 to 528 of SEQ ID NO: 1, or amino acids 330 to 541 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant.

4. The RNA of any one of claims 1-3, wherein the S2 domain comprises amino acid 686-1213 of SEQ ID NO: 1, 686-1211 of SEQ ID NO: 1, amino acids 687-1206 of SEQ ID NO: 1, or amino acids 687-1211 of SEQ ID NO: 1, or a corresponding region of any of the foregoing of an S protein of a SARS-CoV-2 variant, wherein the S2 domain comprises one or more mutations that stabilize the S2 domain.

5. The RNA of any one of claims 1-4, wherein the S2 domain comprises:

(a) an amino acid sequence that is at least 70% identical to:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIKWP;

(b) an amino acid sequence that is at least 70% identical to:

SVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAV EQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGL TVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTAS ALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKM SECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEP QIITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLI DLQELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto;

(c) an amino acid sequence that is at least 70% identical to:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYHLMSFPQSAPHGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKYEQYIK, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto; or

(d) an amino acid sequence that is at least 70% identical to:

VASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVE QDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLT VLPPLLTDEMIAQYTSALLAGTITSGV/FFGAGAALQIPFAMQMAYRFNGIGVFQNVLYENQKLIANQFNSAIGKIQDSLSSTASA LGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMS ECVLGQSKRVDFCGKGYH LM SFPQSAPHG WFLHVTYVPAQEKN FTTAPAICH DGKAH FPREGVFVSNGTHWFVTQRN FYEPQ IITTDNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASWNIQKEIDRLNEVAKNLNESLIDL QELGKY, or a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identical thereto.

6. The RNA of any one of claims 1-5, wherein the S2 domain comprises one or more mutations that can stabilize the prefusion confirmation of an S protein.

7. The RNA of claim 6, wherein the S2 domain comprises one or more of the following mutations relative to SEQ ID NO: 1, or corresponding mutation(s) in an S2 domain of an S protein of a SARS-CoV-2 variant:

(a) K986P and V987P;

(b) A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P;

(c) F817P, A892P, A899P, A942P, or combinations thereof, optionally in combination with K986P and V987P;

(d) V707C and T883C;

(e) I770C and A1015C;

(f) V826C and A1015C;

(g) V826C and L948C;

(h) F970C and G999C;

(i) S735C and T859C; or fl) any combination of (a)-(i).

8. The RNA of any one of claims 1-7, wherein the non-endogenous sequence comprises a flexible linker sequence.

9. The RNA of any one of claims 1-8, wherein the polypeptide does not comprise sequences of a coronavirus S protein other than that of the RBD and the S2 domain or one or more fragments thereof, and wherein: (i) the polypeptide does not comprise a SARS-CoV-2 S protein secretory signal and/or a SARS-CoV- 2 S protein transmembrane domain;

(ii) the polypeptide comprises a SARS-CoV-2 S protein secretory signal and/or a SARS-CoV-2 S protein transmembrane domain.

10. The RNA of any one of claims 1-9, wherein the polypeptide comprises a stem helix (SH) and fusion peptide (FP) of an S2 domain and does not comprise sequences of other regions of the S2 domain, aside from a transmembrane domain of a SARS-CoV-2 S protein.

11. The RNA of claim 10, wherein the RBD is directly adjacent to the SH and/or the FP, or wherein the RBD is connected to the SH and/or the FP via a flexible linker sequence.

12. The RNA of any one of claims 1-11, wherein the SH and the FP are directly adjacent to one another or are connected to one another via a non-endogenous sequence comprising a flexible linker sequence.

13. The RNA of any one of embodiments 1-12, wherein the RBD is N-terminal to the SH and the FP, or the RBD is C-Terminal to the SH and the FP.

14. The RNA of any one of claims 1-13, wherein the N-terminal to C-terminal orientation of the polypeptide is: (RBD)-(FP)-(SH), or (FP)-(SH)-(RBD).

15. The RNA of claim 14, wherein the SH and the FP are directly adjacent to one another, and wherein the RBD is N-terminal or C-terminal to the SH-FP region.

16. The RNA of any one of claims 1-16, wherein the polypeptide comprises a transmembrane domain, wherein the transmembrane domain comprises an amino acid sequence that is at least 70% identical to

EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT or

EQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCC.

17. The RNA of claim 16, wherein the N-terminal to C-terminal orientation of the polypeptide is:

(a) (FP)-(SH)-(RBD)-(transmembrane domain); or

(b) (RBD)-(FP)-(SH)-(transmembrane domain).

18. The RNA of any one of claims 1-17, wherein the FP comprises a sequence that is at least 70% identical to PSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGD, and the SH comprises a sequence that is at least 70% identical to LQPELDSFKEELDKYFKNHTSPDV.

19. The RNA of any one of claims 1-18, wherein the polypeptide comprises a secretory signal peptide, wherein the secretory signal peptide is a homologous or a heterologous secretory signal peptide.

20. The RNA of any one of claims 1-19, wherein the polypeptide comprises a secretory signal peptide comprising:

(i) an amino acid sequence that is at least 70% identical to MFVFLVLLPLVSSQCVNLT, or a sequence of a corresponding region of an S protein of a SARS-CoV-2 variant.

(ii) an amino acid sequence that is at least 70% identical to MCRGLSAVLILLVSLSAQLHVWG;

(Hi) an amino acid sequence that is at least 70% identical to MFLLLRFVLVSCIIGSLG;

(iv) an amino acid sequence that is at least 70% identical to MGGAAARLGAVILFVVIVGLHGVRG;

(v) an amino acid sequence that is at least 70% identical to

MHQGAPSWGRRWFWWALLGLTLGVLVASAAP or an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, 99% or more identical thereto; or

(vi) an amino acid sequence that is at least 70% identical to MARGAGLVFFVGVWVVSCLA.

21. The RNA of any one of claims 1-20, wherein the polypeptide comprises:

(a) an amino acid sequence that is at least 70% identical to SEQ ID NO: 190; or

(b) an amino acid sequence that is at least 70% identical to SEQ ID NO: 191.

22. The RNA of any one of claims 1-21, wherein the RBD comprises one or more mutations of a SARS-CoV-2 variant.

23. The RNA of any one of the preceding claims, wherein the RNA comprises a 5' cap, a cap proximal sequence, a 5' UTR sequence, a 3' UTR sequence, and a polyA sequence; wherein

(i) the 5' cap comprises a Capl structure;

(ii) the 5'-UTR sequence comprises a modified human alpha-globin 5'-UTR;

(iii) the 3 -UTR sequence comprises a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA;

(iv) the polyA sequence comprises at least 100 A nucleotides; or

(v) the RNA comprises a combination of any one of (i)-(iv).

24. The RNA of claim 23, wherein: the 5' cap comprising a Capl structure, and the Capl structure comprises m7(3'OMeG)(5')ppp(5')(2'OMeAl)pG2, wherein Al is position +1 of the RNA, and G2 is position +2 of the RNA, wherein the cap proximal sequence comprises Ai and G2 of the Capl structure, and a sequence comprising: A3N4N5 at positions +3, +4 and +5 respectively of the RNA, wherein N< and Ns are each independently selected from A, G, C, and U; and/or the polyA sequence comprises an interrupted sequence of A nucleotides; and/or the 5'-UTR sequence comprises a sequence that is at least 70% identical to SEQ ID NO: 112; and/or the 3'-UTR sequence comprises a sequence that is at least 70% identical to SEQ ID NO: 113; and/or the sequence at the 5' end of the 3'UTR sequence (e.g., the sequence immediately adjacent to a sequence encoding an antigenic polypeptide) is CUCGAG or GGAUCCGAU.

25. The RNA of any one of the preceding claims, wherein the RNA is self-amplifying RNA (saRNA), transamplifying RNA (taRNA), or messenger RNA (mRNA).

26. The RNA of any one of the preceding claims, wherein the RNA is unmodified RNA or wherein the RNA comprises a single Nl-methyl-pseudouridine in place of each uridine.

27. A composition comprising an RNA of any one of claims 1-26, wherein the RNA is formulated in a lipid nanoparticle, a polyplex (PLX), a lipidated polyplex (LPLX), a liposome, or a polysaccharide nanoparticle.

28. The composition of claim 27, wherein the RNA is fully or partially encapsulated in the nanoparticle.

29. The composition of any one of claims 27-28, further comprising about 10 mM Tris buffer and about 10% sucrose.

30. A pharmaceutical composition comprising (i) an RNA of any one of claims 1-26 or a composition of any one of claims 27-29 and (ii) a pharmaceutically acceptable excipient.

31. The pharmaceutical composition of claim 30, wherein the pharmaceutical composition is formulated as a multi-dose formulation in a vial, a single-dose formulation in a vial, or a prefilled syringe.

32. The pharmaceutical composition of claim 30 or 31, formulated to provide a dose of about 100 pg or less of total RNA, about 90 pg, about 60 pg, about 30 pg, about 25 pg, about 20 pg, about 10 pg, about 6 pg, about 5 pg, or about 3 μg of total RNA.

33. A method comprising administering an RNA of any one of claims 1-26, a composition of any one of claims 27-29, or a pharmaceutical composition of any one of claims 30-32 to a subject.

34. The method of claim 33, wherein:

(i) the subject is 12 years or older, and the method comprises administering 30 pg of the RNA,

(ii) the subject is 5 years to less than 12 years old, and the method comprises administering 10 pg of the RNA, or

(iii) the subject is 6 months to less than 5 years old, and the method comprises administering 3 pg of the RNA.

35. The method of claim 33 or 34, wherein the composition is administered in a volume of about 200 pL to about 300μL.

36. The method of any one of claims 33-35, wherein the method comprises administering a single dose of the RNA, composition, or pharmaceutical composition to the subject.

37. The method of any one of claims 33-36, wherein the method comprises administering two or more doses of the RNA, composition, or pharmaceutical composition to the subject.

38. The method of any one of claims 33-37, wherein RNA, composition, or pharmaceutical composition is administered three times to the subject.

39. The method of any one of claims 33-38, further comprising administering one or more vaccines against a non-SARS-CoV-2 disease.

40. The method of any one of claims 33-39, wherein the method results in induction of an immune response against SARS-CoV-2 in the subject.

41. The method of any one of claims 33-40, wherein the method is a method of preventing SARS-CoV-2 infection, reducing the chance of SARS-CoV-2 infection, preventing or reducing the change of deleterious symptoms associated with SARS-CoV-2 infection (which can result, e.g., in a reduced change of hospitalization), increase the change of experiencing an asymptomatic SARS-CoV-2 infection, and/or treating a SARS-CoV-2 infection.

42. An RNA of any one of claims 1-26, a composition of any one of claims 27-29, or a pharmaceutical composition of any one of claims 30-32, for use in inducing an immune response in a subject.

43. Use of an RNA of any one of claims 1-26, a composition of any one of claims 27-29, or a pharmaceutical composition of any one of claims 30-32, for the manufacture of a medicament for inducing an immune response in a subject.

44. A method of manufacturing an RNA, comprising in vitro transcribing the RNA of any one of claims 1-26.