US20180282728A1 - Organic compositions to treat beta-catenin-related diseases - Google Patents

Abstract

The present disclosure relates to RNAi agents useful in methods of treating Beta-Catenin-related diseases such as adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases, using a therapeutically effective amount of a RNAi agent to Beta-Catenin.

Description

BACKGROUND OF THE INVENTION
• Signaling by the Wnt family of secreted glycolipoproteins is one of the fundamental mechanisms that direct cell proliferation, cell polarity, and cell fate determination during embryonic development and tissue homeostasis. As a result, mutations in the Wnt pathway are often linked to human birth defects, cancer, and other diseases. A critical Wnt pathway is the canonical Wnt signaling pathway.
• The transcriptional co-activator Beta-Catenin is the molecular node in this pathway. In the absence of Wnt, cytoplasmic Beta-catenin protein is constantly degraded by the action of the Axin complex, which is composed of the scaffolding protein Axin, the tumor suppressor adenomatous polyposis coli gene product (APC), casein kinase 1 (CK1), and glycogen synthase kinase 3 (GSK3). CK1 and GSK3 sequentially phosphorylate the amino terminal region of Beta-catenin, resulting in Beta-catenin recognition by Beta-Trcp, an E3 ubiquitin ligase subunit, and subsequent Beta-catenin ubiquitination and proteasomal degradation.
• This continual elimination of Beta-catenin prevents Beta-catenin from reaching the nucleus, and Wnt target genes are thereby repressed by the DNA-bound T cell factor/lymphoid enhancer factor (TCF/LEF) family of proteins. The Wnt/Beta-catenin pathway is activated when a Wnt ligand binds to the seven-pass transmembrane Frizzled (Fz or Fzd) receptor and its coreceptor, low-density lipoprotein receptor-related protein 6 (LRP6), or its close relative LRP5. The formation of a likely Wnt-Fz-LRP6 complex, together with the recruitment of the scaffolding protein Dishevelled (Dvl), results in LRP6 phosphorylation and activation and the recruitment of the Axin complex to the receptors. These events lead to inhibition of Axin-mediated Beta-catenin phosphorylation and thereby to the stabilization of Beta-catenin, which accumulates, travels to the nucleus to form complexes with TCF/LEF and activates Wnt target gene expression.
• Given the critical roles of Wnt/Beta-catenin signaling in development and homeostasis, it is no surprise that mutations of the Wnt pathway components are associated with many disorders and diseases. McDonald et al. 2009 Dev. Cell 17: 9-26. Association of deregulated Wnt/Beta-catenin signaling with cancer has been well documented, particularly with colorectal cancer. Polakis 2007. Curr. Opin. Genet. Dev. 17: 45-51. Constitutively activated Beta-catenin signaling, due to APC deficiency or Beta-catenin mutations that prevent its degradation, leads to excessive stem cell renewal/proliferation that predisposes cells to tumorigenesis. Indeed, APC deletion or Beta-catenin activation in stem cells is essential for intestinal neoplasia. Fuchs 2009 Cell 137: 811-819.
• Mutations in Beta-Catenin, alterations of levels and cellular compartmentalization of Beta-Catenin, and other aberrations of the Wnt/Beta-Catenin pathway are thus involved directly or indirectly with many diseases. In some Beta-Catenin-related cancers, Beta-Catenin is required for tumor growth but is not amplified, over-expressed or mis-localized.
• There exists the need for treatments related to Beta-Catenin-related diseases.
BRIEF SUMMARY OF THE INVENTION
• The present disclosure provides RNAi (RNA interference) agents to Beta-Catenin, for inhibition of the target gene Beta-Catenin, which are useful in the treatment of Beta-Catenin-related diseases, such as adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases. The present disclosure also encompasses a method of treating a human subject having a pathological state mediated at least in part by Beta-Catenin expression, the method comprising the step of administering to the subject a therapeutically effect amount of a RNAi agent to Beta-Catenin.
• The present disclosure provides specific RNAi agents and methods that are useful in reducing Beta-Catenin levels in a subject, e.g., a mammal, such as a human. The present disclosure specifically provides double-stranded RNAi agents comprising at least 15 or more contiguous nucleotides of Beta-Catenin. In particular, the present disclosure provides agents comprising a sense strand and an anti-sense strand, wherein the sense strand and/or the anti-sense strand comprise sequences of 15 or more contiguous nucleotides differing by 0, 1, 2 or 3 from those of the RNAi agents provided, e.g., in Table 1 or elsewhere herein, and modified and unmodified variants thereof. Unmodified sequences are sometimes referred to as “generic”. The present disclosure also provides agents comprising a sense strand and an anti-sense strand, wherein the sense strand and/or the anti-sense strand comprise sequences of 19 or more contiguous nucleotides differing by 0, 1, 2 or 3 from those of the RNAi agents provided, e.g., in Table 1 or elsewhere herein, and modified and unmodified variants thereof. The sense strand and anti-sense strand can be contiguous, or covalently bound, e.g., via a loop or linker. The RNAi agents particularly can in one embodiment comprise less than about 30 nucleotides per strand, e.g., such as 17 to 23 nucleotides, 18 to 22 nucleotides, 17 to 23 nucleotides, and/or 19 to 21 nucleotides, and/or 19 to 30 nucleotides, and/or such as those provided, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9 or elsewhere herein.
• The double-stranded RNAi agents can have 0, 1 or 2 blunt ends, and/or overhangs of 1, 2, 3 or 4 nucleotides (i.e., 1 to 4 nt) from one or both 3′ and/or 5′ ends. The double-stranded RNAi agents can also optionally comprise one or two 3′ caps and/or one or more modified nucleotides. Modified variants of sequences as provided herein include those that are otherwise identical but contain substitutions of a naturally-occurring nucleotide for a corresponding modified nucleotide.
• Further, the RNAi agent can either contain only naturally-occurring ribonucleotide subunits, or one or more modifications to the sugar, phosphate or base of one or more of the replacement nucleotide subunits, whether they comprise ribonucleotide subunits or deoxyribonucleotide subunits. In one embodiment, modified variants of the disclosed RNAi agents have a thymidine (as RNA, or, preferably, DNA) replacing a uridine. In one embodiment, modified variants of the disclosed RNAi agents include RNAi agents with the same sequence (e.g., the same sequence of bases), but with one or more modifications to one or more of the sugar, phosphate or base of one or more of the nucleotide subunits. In one embodiment, the modifications improve efficacy, stability (e.g., against nucleases in blood serum and/or intestinal fluid), and/or reduce immunogenicity of the RNAi agent. One aspect of the present disclosure relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a particular embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands contain a non-natural nucleobase.
• The RNAi agent(s) can optionally be attached to a ligand selected to improve one or more characteristics, e.g., stability, distribution and/or cellular uptake of the agent, e.g. cholesterol or a derivative thereof. The RNAi agent(s) can be isolated or part of a pharmaceutical composition used for the methods described herein. The pharmaceutical compositions can optionally comprise two or more RNAi agents, each one directed to the same or a different segment the Beta-Catenin mRNA. Optionally, the pharmaceutical compositions can further comprise or be used in conjunction with any known treatment for any Beta-Catenin-related disease.
• The present disclosure further provides methods for reducing the level of Beta-Catenin mRNA in a cell, particularly in the case of a disease characterized by over-expression or hyper-activity of Beta-Catenin. Such methods comprise the step of administering one or more of the RNAi agents of the present disclosure to a cell, as further described below. The present methods utilize the cellular mechanisms involved in RNA interference to selectively degrade the target RNA in a cell and are comprised of the step of contacting a cell with one of the RNAi agents of the present disclosure. The present disclosure also encompasses a method of treating a human subject having a pathological state mediated at least in part by Beta-Catenin expression, over-expression, hyper-activity or improper cellular compartmentalization, the method comprising the step of administering to the subject a therapeutically effect amount of a RNAi agent to Beta-Catenin. Additional methods involve a pathological state wherein disease progression (e.g., tumor growth) requires Beta-Catenin, although Beta-Catenin is not amplified, over-expressed or mis-localized. Such methods can be performed directly on a cell or can be performed on a mammalian subject by administering to a cell or a subject one or more of the RNAi agents/pharmaceutical compositions of the present disclosure. Reduction of target Beta-Catenin RNA in a cell results in a reduction in the amount of encoded Beta-Catenin protein produced. In an organism, this can result in restoration of balance in the Wnt/Beta-Catenin pathway, and/or prevention of Beta-Catenin accumulation, and/or restoration of proper cell compartmentalization of Beta-Catenin, and/or a reduction in Beta-Catenin activity and/or expression, and/or prevention of Beta-Catenin-mediated activation of Wnt-related genes such as the proto-oncogene c-myc, and/or amelioration, treatment and/or prevention of a Beta-Catenin-related disease. In some Beta-Catenin-related cancers, Beta-Catenin is required for tumor growth but is not amplified, over-expressed or mis-localized. A reduction in Beta-Catenin expression, level or activity should thus limit tumor growth.
• The methods and compositions of the present disclosure, e.g., the methods and Beta-Catenin RNAi agent compositions, can be used with any dosage and/or formulation described herein, as well as with any route of administration described herein.
• The details of one or more embodiments of the present disclosure are set forth in the accompanying drawings and the description below. Elements of the various embodiments (e.g., sequences, modifications, endcaps, combinations of RNAi agents, ligands, additional treatments or methods which can be used, etc.) which are not mutually-exclusive can be combined with each other. Combinations which are mutually exclusive include, for example, the fact that a RNAi agent comprising two strands cannot by definition have both two blunt ends and two overhangs. Furthermore, any RNAi agent sequence can be combined with any set of modifications or endcaps disclosed herein, provided the elements of the combination are not mutually exclusive. Any combination of modifications, 5′ end caps, and/or 3′ end caps can be used with any RNAi agent sequence disclosed herein. Any RNAi agent can be combined with any other RNAi agent or other treatment composition or method. Other features, objects, and advantages of the present disclosure will be apparent from this description, the drawings, and from the claims.
BRIEF DESCRIPTION OF THE FIGURES
• FIG. 1 illustrates various modified nucleotides: U002, U003, U004, U005, C004, C005, A004, A005, G005, and G004, which can be used in the RNAi agents disclosed herein. U002 indicates a 2′-deoxy-thymidine which is DNA. U003 indicates 2′-deoxy uridine. U004 indicates a nucleotide with a U base with a 2′-O-methyl modification. U005 indicates a U base with a 2′-O-methoxyethyl (MOE) modification. C004 indicates a C base with a 2′-O-methyl modification. C005 indicates a C base with 2′-O-methoxyethyl modification. A004 indicates an A base with a 2′-O-methyl modification. A005 indicates an A base with 2′-O-methoxyethyl modification. G005 indicates a G base with a 2′O-methyl modification. G004 indicates a G base with a 2′O-methyl modification. Polynucleotide sequences written with the symbols U002, U003, U004, etc. are sometimes prefaced by “X” (indicating the start of the sequence), and sometimes have a “p” between the bases, indicating the phosphodiester bond between nucleosides.
DETAILED DESCRIPTION OF THE INVENTION
• The present disclosure encompasses RNAi agents to Beta-Catenin, for inhibition of the target gene Beta-Catenin, which are useful in treatment of Beta-Catenin-related diseases (e.g., diseases associated with mutations in and/or altered expression, compartmentalization, level and/or activity of Beta-Catenin, and/or diseases treatable by modulating the expression, level and/or activity of Beta-Catenin), such as adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases. In some Beta-Catenin-related cancers, Beta-Catenin is required for tumor growth but is not amplified, over-expressed or mis-localized. A reduction in Beta-Catenin expression, level or activity should thus limit tumor growth. The present disclosure also encompasses a method of treating a human subject having a pathological state mediated at least in part by Beta-Catenin expression, the method comprising the step of administering to the subject a therapeutically effect amount of a RNAi agent to Beta-Catenin.
• Various Embodiments of the Present Disclosure Include:
• RNAi Agent Comprising an Anti-Sense Strand of a RNAi Agent Described Herein.
• In one embodiment, the present disclosure relates to a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-Catenin (or any set of overlapping RNAi agents specific to Beta-Catenin) provided, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In another embodiment, the present disclosure relates to a composition comprising a RNAi agent comprising a sense and an anti-sense strand, wherein the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sense strand of a RNAi agent from any sequence provided herein. In another embodiment, the present disclosure relates to a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sequence of the first strand, and the second strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sequence of the second strand of any RNAi agent provided herein. In another embodiment, the present disclosure relates to a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand comprises the sequence of the first strand of any RNAi agent provided herein. In another embodiment, the present disclosure relates to a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand is the sequence of the first strand of any RNAi agent provided herein. In another embodiment, the present disclosure relates to a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the sequences of the first and/or second strands comprise the sequences of the first and/or second strand of any RNAi agent provided herein. In another embodiment, the present disclosure relates to a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the sequences of the first and/or second strand are the sequences of the first and/or second strand of any RNAi agent provided herein. In these various embodiments, the RNAi agent is for inhibition of the target gene Beta-Catenin.
• Particular duplexes include the unmodified and example modified sequences listed in Table 1. In addition to the described example modifications, other modified variants can be made using the nucleotide sequences provided.

• TABLE 1
  SEQ ID NOs. for RNAi Agents to Beta-Catenin
  Provided in Table 1 are the nickname of various Beta-Catenin
  RNAi duplexes; the unmodified sense and anti-sense
  sequences and SEQ ID NOs; an example modified sense
  and antisense sequence and SEQ ID NOs; and the position
  of the RNAi agent within the Beta-Catenin gene.

  EXAMPLE

  	UNMODIFIED	MODIFIED
  	SEQUENCE	SEQUENCE

  	Sense	Anti-sense	Sense
  	SEQ ID	SEQ ID	SEQ ID	Anti-sense
  DUPLEX	NO:	NO:	NO:	SEQ NO:	Position

  AD-18892	4771	5430	1	6497	2500
  AD-18893	4772	5431	2	661	1659
  AD-18894	4773	5432	3	662	3038
  AD-18895	4774	5433	4	663	2096
  AD-18896	4775	5434	5	664	265
  AD-18897	4776	5435	6	665	1797
  AD-18898	4777	5436	7	666	2587
  AD-18899	4778	5437	8	667	1541
  AD-18900	4779	5438	9	668	2391
  AD-18901	4780	5439	10	669	954
  AD-18902	4781	5440	11	670	2908
  AD-18903	4782	5441	12	671	3104
  AD-18904	4783	5442	13	672	1665
  AD-18905	4784	5443	14	673	2594
  AD-18906	4785	5444	15	674	3147
  AD-18907	4786	5445	16	675	2592
  AD-18908	4787	5446	17	676	2507
  AD-18909	4788	5447	18	677	2325
  AD-18910	4789	5448	19	678	2326
  AD-18911	4790	5449	20	679	577
  AD-18912	4791	5450	21	680	2116
  AD-18913	4792	5451	22	681	2708
  AD-18914	4793	5452	23	682	2912
  AD-18915	4794	5453	24	683	2704
  AD-18916	4795	5454	25	684	3146
  AD-18917	4796	5455	26	685	1542
  AD-18918	4797	5456	27	686	621
  AD-18919	4798	5457	28	687	2505
  AD-18920	4799	5458	29	688	2590
  AD-18921	4800	5459	30	689	3099
  AD-18922	4801	5460	31	690	2591
  AD-18923	4802	5461	32	691	2112
  AD-18925	4803	5462	33	692	366
  AD-18926	4804	5463	34	693	2479
  AD-18927	4805	5464	35	694	1502
  AD-18928	4806	5465	36	695	2073
  AD-18929	4807	5466	37	696	2702
  AD-18930	4808	5467	38	697	1774
  AD-18931	4809	5468	39	698	708
  AD-18932	4810	5469	40	699	1667
  AD-18933	4811	5470	41	700	2629
  AD-18934	4812	5471	42	701	2114
  AD-18935	4813	5472	43	702	2706
  AD-18936	4814	5473	44	703	2899
  AD-18937	4815	5474	45	704	1639
  AD-18938	4816	5475	46	705	1638
  AD-18939	4817	5476	47	706	2906
  AD-18940	4818	5477	48	707	3145
  AD-18941	4819	5478	49	708	2390
  AD-18942	4820	5479	50	709	2707
  AD-18943	4821	5480	51	710	1668
  AD-18944	4822	5481	52	711	2506
  AD-18945	4823	5482	53	712	1286
  AD-18946	4824	5483	54	713	1660
  AD-18947	4825	5484	55	714	2328
  AD-18948	4826	5485	56	715	1776
  AD-18949	4827	5486	57	716	619
  AD-18950	4828	5487	58	717	807
  AD-18951	4829	5488	59	718	2417
  AD-18952	4830	5489	60	719	3165
  AD-18953	4831	5490	61	720	266
  AD-18954	4832	5491	62	721	618
  AD-18955	4833	5492	63	722	2113
  AD-18956	4834	5493	64	723	3040
  AD-18957	4835	5494	65	724	3166
  AD-18958	4836	5495	66	725	3041
  AD-18959	4837	5496	67	726	582
  AD-18960	4838	5497	68	727	3220
  AD-18961	4839	5498	69	728	2125
  AD-18962	4840	5499	70	729	2101
  AD-18963	4841	5500	71	730	1773
  AD-18964	4842	5501	72	731	2588
  AD-18965	4843	5502	73	732	2598
  AD-18966	4844	5503	74	733	2907
  AD-18967	4845	5504	75	734	2508
  AD-18968	4846	5505	76	735	3102
  AD-18969	4847	5506	77	736	3042
  AD-18970	4848	5507	78	737	2499
  AD-18971	4849	5508	79	738	2124
  AD-18972	4850	5509	80	739	3105
  AD-18973	4851	5510	81	740	2119
  AD-18974	4852	5511	82	741	641
  AD-18975	4853	5512	83	742	2584
  AD-18976	4854	5513	84	743	2105
  AD-18977	4855	5514	85	744	1069
  AD-18978	4856	5515	86	745	2330
  AD-18979	4857	5516	87	746	2388
  AD-18980	4858	5517	88	747	3224
  AD-18981	4859	5518	89	748	3098
  AD-18982	4860	5519	90	749	2049
  AD-18983	4861	5520	91	750	1796
  AD-18984	4862	5521	92	751	2127
  AD-18985	4863	5522	93	752	3029
  AD-18986	4864	5523	94	753	2596
  AD-18987	4865	5524	95	754	3221
  AD-18988	4866	5525	96	755	3159
  AD-18989	4867	5526	97	756	2583
  AD-18990	4868	5527	98	757	1655
  AD-18991	4869	5528	99	758	874
  AD-18992	4870	5529	100	759	3028
  AD-18993	4871	5530	101	760	3037
  AD-18994	4872	5531	102	761	1504
  AD-18995	4873	5532	103	762	3095
  AD-18996	4874	5533	104	763	2703
  AD-18997	4875	5534	105	764	3154
  AD-18998	4876	5535	106	765	3094
  AD-18999	4877	5536	107	766	2599
  AD-19000	4878	5537	108	767	643
  AD-19001	4879	5538	109	768	2389
  AD-19002	4880	5539	110	769	1669
  AD-19003	4881	5540	111	770	2106
  AD-19004	4882	5541	112	771	3170
  AD-19005	4883	5542	113	772	3103
  AD-19006	4884	5543	114	773	642
  AD-19007	4885	5544	115	774	3230
  AD-19008	4886	5545	116	775	3222
  AD-19009	4887	5546	117	776	2905
  AD-19010	4888	5547	118	777	2904
  AD-19011	4889	5548	119	778	579
  AD-19012	4890	5549	120	779	3171
  AD-19042	4891	5550	121	780	2504
  AD-19043	4892	5551	122	781	3039
  AD-19044	4893	5552	123	782	3034
  AD-19045	4894	5553	124	783	1505
  AD-19046	4895	5554	125	784	1288
  AD-19047	4896	5555	126	785	2123
  AD-19048	4897	5556	127	786	620
  AD-19049	4898	5557	128	787	3164
  AD-19050	4899	5558	129	788	3101
  AD-19051	4900	5559	130	789	2329
  AD-19052	4901	5560	131	790	2115
  AD-19053	4902	5561	132	791	2627
  AD-19054	4903	5562	133	792	2902
  AD-19055	4904	5563	134	793	262
  AD-19056	4905	5564	135	794	1406
  AD-19057	4906	5565	136	795	2497
  AD-19058	4907	5566	137	796	3043
  AD-19059	4908	5567	138	797	2589
  AD-19060	4909	5568	139	798	2586
  AD-19061	4910	5569	140	799	1658
  AD-19062	4911	5570	141	800	2050
  AD-19063	4912	5571	142	801	2385
  AD-19064	4913	5572	143	802	1637
  AD-19065	4914	5573	144	803	707
  AD-19066	4915	5574	145	804	2597
  AD-19067	4916	5575	146	805	3161
  AD-19068	4917	5576	147	806	875
  AD-19069	4918	5577	148	807	3044
  AD-19070	4919	5578	149	808	617
  AD-19071	4920	5579	150	809	2498
  AD-19072	4921	5580	151	810	367
  AD-19073	4922	5581	152	811	2545
  AD-19074	4923	5582	153	812	1544
  AD-19075	4924	5583	154	813	3148
  AD-19076	4925	5584	155	814	2909
  AD-19077	4926	5585	156	815	2509
  AD-19078	4927	5586	157	816	1775
  AD-19079	4928	5587	158	817	1407
  AD-19080	4929	5588	159	818	2327
  AD-19081	4930	5589	160	819	3031
  AD-19082	4931	5590	161	820	1661
  AD-19083	4932	5591	162	821	3162
  AD-19738	4933	5592	163	822	1906
  AD-19739	4934	5593	164	823	825
  AD-19740	4935	5594	165	824	1838
  AD-19741	4936	5595	166	825	1714
  AD-19742	4937	5596	167	826	1859
  AD-19743	4938	5597	168	827	324
  AD-19744	4939	5598	169	828	535
  AD-19745	4940	5599	170	829	822
  AD-19746	4941	5600	171	830	826
  AD-19747	4942	5601	172	831	851
  AD-19748	4943	5602	173	832	1313
  AD-19749	4944	5603	174	833	1860
  AD-19750	4945	5604	175	834	2016
  AD-19751	4946	5605	176	835	1868
  AD-19752	4947	5606	177	836	1869
  AD-19753	4948	5607	178	837	1876
  AD-19754	4949	5608	179	838	1908
  AD-19755	4950	5609	180	839	2192
  AD-19756	4951	5610	181	840	520
  AD-19757	4952	5611	182	841	524
  AD-19758	4953	5612	183	842	623
  AD-19759	4954	5613	184	843	916
  AD-19760	4955	5614	185	844	1153
  AD-19761	4956	5615	186	845	1677
  AD-19762	4957	5616	187	846	1864
  AD-19763	4958	5617	188	847	246
  AD-19765	4959	5618	189	848	637
  AD-19766	4960	5619	190	849	823
  AD-19767	4961	5620	191	850	1028
  AD-19768	4962	5621	192	851	1314
  AD-20124	4963	5622	193	852	2012
  AD-25889	4964	5623	194	853	2632
  AD-25890	4965	5624	195	854	2637
  AD-25891	4966	5625	196	855	2648
  AD-25892	4967	5626	197	856	2649
  AD-25893	4968	5627	198	857	2663
  AD-25894	4969	5628	199	858	2664
  AD-25895	4970	5629	200	859	2694
  AD-25896	4971	5630	201	860	2695
  AD-25897	4972	5631	202	861	2697
  AD-25898	4973	5632	203	862	2698
  AD-25899	4974	5633	204	863	2699
  AD-25900	4975	5634	205	864	2751
  AD-25901	4976	5635	206	865	2752
  AD-25902	4977	5636	207	866	2753
  AD-25903	4978	5637	208	867	2832
  AD-25904	4979	5638	209	868	2833
  AD-25905	4980	5639	210	869	2837
  AD-25906	4981	5640	211	870	2843
  AD-25907	4982	5641	212	871	2844
  AD-25908	4983	5642	213	872	2845
  AD-25909	4984	5643	214	873	2846
  AD-25910	4985	5644	215	874	2859
  AD-25911	4986	5645	216	875	2913
  AD-25912	4987	5646	217	876	2914
  AD-25913	4988	5647	218	877	2938
  AD-25914	4989	5648	219	878	2940
  AD-25915	4990	5649	220	879	2941
  AD-25916	4991	5650	221	880	2942
  AD-25917	4992	5651	222	881	2991
  AD-25918	4993	5652	223	882	2992
  AD-25919	4994	5653	224	883	2997
  AD-25920	4995	5654	225	884	2998
  AD-25921	4996	5655	226	885	3077
  AD-25922	4997	5656	227	886	3078
  AD-25923	4998	5657	228	887	3080
  AD-25924	4999	5658	229	888	3083
  AD-25925	5000	5659	230	889	3110
  AD-25926	5001	5660	231	890	3111
  AD-25927	5002	5661	232	891	3112
  AD-25928	5003	5662	233	892	3123
  AD-25929	5004	5663	234	893	3124
  AD-25930	5005	5664	235	894	3125
  AD-25931	5006	5665	236	895	3132
  AD-25932	5007	5666	237	896	3133
  AD-25933	5008	5667	238	897	3135
  AD-25934	5009	5668	239	898	3168
  AD-25935	5010	5669	240	899	3169
  AD-25936	5011	5670	241	900	3172
  AD-25937	5012	5671	242	901	3192
  AD-25938	5013	5672	243	902	2665
  AD-25939	5014	5673	244	903	2682
  AD-25940	5015	5674	245	904	2683
  AD-25941	5016	5675	246	905	2684
  AD-25942	5017	5676	247	906	2685
  AD-25943	5018	5677	248	907	2686
  AD-25944	5019	5678	249	908	2687
  AD-25945	5020	5679	250	909	2696
  AD-25946	5021	5680	251	910	2709
  AD-25947	5022	5681	252	911	2710
  AD-25948	5023	5682	253	912	2711
  AD-25949	5024	5683	254	913	2712
  AD-25950	5025	5684	255	914	2713
  AD-25951	5026	5685	256	915	2714
  AD-25952	5027	5686	257	916	2834
  AD-25953	5028	5687	258	917	2835
  AD-25954	5029	5688	259	918	2836
  AD-25955	5030	5689	260	919	2842
  AD-25956	5031	5690	261	920	2847
  AD-25957	5032	5691	262	921	2848
  AD-25958	5033	5692	263	922	2871
  AD-25959	5034	5693	264	923	2993
  AD-25960	5035	5694	265	924	2996
  AD-25961	5036	5695	266	925	3079
  AD-25962	5037	5696	267	926	3084
  AD-25963	5038	5697	268	927	3092
  AD-25964	5039	5698	269	928	3109
  AD-26017	5040	5699	270	929	3152
  AD-26018	5041	5700	271	930	3170
  AD-26019	5042	5701	272	931	3171
  AD-26020	5043	5702	273	932	3198
  AD-26021	5044	5703	274	933	3199
  AD-26022	5045	5704	275	934	207
  AD-26023	5046	5705	276	935	208
  AD-26024	5047	5706	277	936	215
  AD-26025	5048	5707	278	937	216
  AD-26026	5049	5708	279	938	217
  AD-26027	5050	5709	280	939	221
  AD-26028	5051	5710	281	940	222
  AD-26029	5052	5711	282	941	225
  AD-26030	5053	5712	283	942	230
  AD-26031	5054	5713	284	943	231
  AD-26032	5055	5714	285	944	232
  AD-26033	5056	5715	286	945	235
  AD-26034	5057	5716	287	946	236
  AD-26035	5058	5717	288	947	251
  AD-26036	5059	5718	289	948	252
  AD-26037	5060	5719	290	949	257
  AD-26038	5061	5720	291	950	262
  AD-26039	5062	5721	292	951	268
  AD-26040	5063	5722	293	952	269
  AD-26041	5064	5723	294	953	270
  AD-26042	5065	5724	295	954	273
  AD-26043	5066	5725	296	955	285
  AD-26044	5067	5726	297	956	291
  AD-26045	5068	5727	298	957	295
  AD-26046	5069	5728	299	958	305
  AD-26047	5070	5729	300	959	307
  AD-26048	5071	5730	301	960	111
  AD-26049	5072	5731	302	961	316
  AD-26050	5073	5732	303	962	317
  AD-26051	5074	5733	304	963	331
  AD-26052	5075	5734	305	964	338
  AD-26053	5076	5735	306	965	339
  AD-26054	5077	5736	307	966	353
  AD-26055	5078	5737	308	967	354
  AD-26056	5079	5738	309	968	358
  AD-26057	5080	5739	310	969	1216
  AD-26058	5081	5740	311	970	383
  AD-26059	5082	5741	312	971	397
  AD-26060	5083	5742	313	972	402
  AD-26061	5084	5743	314	973	412
  AD-26062	5085	5744	315	974	418
  AD-26063	5086	5745	316	975	424
  AD-26064	5087	5746	317	976	441
  AD-26065	5088	5747	318	977	442
  AD-26066	5089	5748	319	978	451
  AD-26067	5090	5749	320	979	458
  AD-26068	5091	5750	321	980	1232
  AD-26069	5092	5751	322	981	1233
  AD-26070	5093	5752	323	982	460
  AD-26071	5094	5753	324	983	461
  AD-26072	5095	5754	325	984	471
  AD-26073	5096	5755	326	985	478
  AD-26074	5097	5756	327	986	481
  AD-26075	5098	5757	328	987	487
  AD-26076	5099	5758	329	988	493
  AD-26077	5100	5759	330	989	507
  AD-26078	5101	5760	331	990	512
  AD-26079	5102	5761	332	991	532
  AD-26080	5103	5762	333	992	542
  AD-26081	5104	5763	334	993	543
  AD-26082	5105	5764	335	994	546
  AD-26083	5106	5765	336	995	558
  AD-26084	5107	5766	337	996	559
  AD-26085	5108	5767	338	997	562
  AD-26086	5109	5768	339	998	576
  AD-26087	5110	5769	340	999	581
  AD-26088	5111	5770	341	1000	584
  AD-26089	5112	5771	342	1001	591
  AD-26090	5113	5772	343	1002	595
  AD-26091	5114	5773	344	1003	604
  AD-26092	5115	5774	345	1004	611
  AD-26093	5116	5775	346	1005	612
  AD-26094	5117	5776	347	1006	613
  AD-26095	5118	5777	348	1007	623
  AD-26096	5119	5778	349	1008	635
  AD-26097	5120	5779	350	1009	642
  AD-26098	5121	5780	351	1010	648
  AD-26099	5122	5781	352	1011	649
  AD-26100	5123	5782	353	1012	652
  AD-26101	5124	5783	354	1013	658
  AD-26102	5125	5784	355	1014	662
  AD-26103	5126	5785	356	1015	666
  AD-26104	5127	5786	357	1016	669
  AD-26105	5128	5787	358	1017	670
  AD-26106	5129	5788	359	1018	672
  AD-26107	5130	5789	360	1019	682
  AD-26108	5131	5790	361	1020	685
  AD-26109	5132	5791	362	1021	691
  AD-26110	5133	5792	363	1022	707
  AD-26111	5134	5793	364	1023	708
  AD-26112	5135	5794	365	1024	715
  AD-26123	5136	5795	366	1025	722
  AD-26124	5137	5796	367	1026	723
  AD-26125	5138	5797	368	1027	724
  AD-26126	5139	5798	369	1028	730
  AD-26127	5140	5799	370	1029	731
  AD-26128	5141	5800	371	1030	732
  AD-26129	5142	5801	372	1031	733
  AD-26130	5143	5802	373	1032	755
  AD-26131	5144	5803	374	1033	756
  AD-26132	5145	5804	375	1034	757
  AD-26133	5146	5805	376	1035	758
  AD-26134	5147	5806	377	1036	1548
  AD-26135	5148	5807	378	1037	1551
  AD-26136	5149	5808	379	1038	759
  AD-26137	5150	5809	380	1039	778
  AD-26138	5151	5810	381	1040	785
  AD-26139	5152	5811	382	1041	788
  AD-26140	5153	5812	383	1042	789
  AD-26141	5154	5813	384	1043	1624
  AD-26142	5155	5814	385	1044	790
  AD-26143	5156	5815	386	1045	791
  AD-26144	5157	5816	387	1046	812
  AD-26145	5158	5817	388	1047	813
  AD-26146	5159	5818	389	1048	816
  AD-26147	5160	5819	390	1049	821
  AD-26148	5161	5820	391	1050	831
  AD-26149	5162	5821	392	1051	842
  AD-26150	5163	5822	393	1052	843
  AD-26151	5164	5823	394	1053	851
  AD-26152	5165	5824	395	1054	855
  AD-26153	5166	5825	396	1055	861
  AD-26154	5167	5826	397	1056	862
  AD-26155	5168	5827	398	1057	866
  AD-26156	5169	5828	399	1058	871
  AD-26157	5170	5829	400	1059	874
  AD-26158	5171	5830	401	1060	877
  AD-26159	5172	5831	402	1061	887
  AD-26160	5173	5832	403	1062	903
  AD-26161	5174	5833	404	1063	907
  AD-26162	5175	5834	405	1064	909
  AD-26163	5176	5835	406	1065	913
  AD-26164	5177	5836	407	1066	914
  AD-26165	5178	5837	408	1067	919
  AD-26166	5179	5838	409	1068	960
  AD-26167	5180	5839	410	1069	975
  AD-26168	5181	5840	411	1070	976
  AD-26169	5182	5841	412	1071	977
  AD-26170	5183	5842	413	1072	978
  AD-26171	5184	5843	414	1073	982
  AD-26172	5185	5844	415	1074	986
  AD-26173	5186	5845	416	1075	997
  AD-26174	5187	5846	417	1076	998
  AD-26175	5188	5847	418	1077	1848
  AD-26176	5189	5848	419	1078	1849
  AD-26177	5190	5849	420	1079	1005
  AD-26178	5191	5850	421	1080	1008
  AD-26179	5192	5851	422	1081	1009
  AD-26180	5193	5852	423	1082	1010
  AD-26181	5194	5853	424	1083	1011
  AD-26182	5195	5854	425	1084	1012
  AD-26183	5196	5855	426	1085	1018
  AD-26184	5197	5856	427	1086	1927
  AD-26185	5198	5857	428	1087	1019
  AD-26186	5199	5858	6495	1088	1022
  AD-26187	5200	5859	6496	1089	1032
  AD-26188	5201	5860	431	1090	1036
  AD-26189	5202	5861	432	1091	1037
  AD-26190	5203	5862	433	1092	1038
  AD-26191	5204	5863	434	1093	1039
  AD-26192	5205	5864	435	1094	1040
  AD-26193	5206	5865	436	1095	1041
  AD-26194	5207	5866	437	1096	1042
  AD-26195	5208	5867	438	1097	1048
  AD-26196	5209	5868	439	1098	1051
  AD-26197	5210	5869	440	1099	1058
  AD-26198	5211	5870	441	1100	1059
  AD-26199	5212	5871	442	1101	1061
  AD-26200	5213	5872	443	1102	1062
  AD-26201	5214	5873	444	1103	1073
  AD-26202	5215	5874	445	1104	1075
  AD-26203	5216	5875	446	1105	1110
  AD-26204	5217	5876	447	1106	206
  AD-26205	5218	5877	448	1107	1113
  AD-26206	5219	5878	449	1108	1114
  AD-26207	5220	5879	450	1109	1115
  AD-26208	5221	5880	451	1110	1118
  AD-26209	5222	5881	452	1111	1119
  AD-26210	5223	5882	453	1112	1139
  AD-26211	5224	5883	454	1113	1153
  AD-26212	5225	5884	455	1114	1185
  AD-26213	5226	5885	456	1115	1220
  AD-26214	5227	5886	457	1116	1221
  AD-26215	5228	5887	458	1117	1222
  AD-26216	5229	5888	459	1118	1225
  AD-26217	5230	5889	460	1119	1226
  AD-26218	5231	5890	461	1120	1227
  AD-26651	5232	5891	462	1121	1228
  AD-26652	5233	5892	463	1122	1229
  AD-26653	5234	5893	464	1123	1230
  AD-26654	5235	5894	465	1124	1231
  AD-26655	5236	5895	466	1125	1242
  AD-26656	5237	5896	467	1126	1243
  AD-26657	5238	5897	468	1127	1244
  AD-26658	5239	5898	469	1128	1247
  AD-26659	5240	5899	470	1129	1271
  AD-26660	5241	5900	471	1130	1284
  AD-26661	5242	5901	472	1131	1291
  AD-26662	5243	5902	473	1132	1292
  AD-26663	5244	5903	474	1133	1337
  AD-26664	5245	5904	475	1134	1338
  AD-26665	5246	5905	476	1135	1346
  AD-26666	5247	5906	477	1136	1347
  AD-26667	5248	5907	478	1137	1366
  AD-26668	5249	5908	479	1138	1370
  AD-26669	5250	5909	480	1139	1375
  AD-26670	5251	5910	481	1140	1381
  AD-26671	5252	5911	482	1141	1384
  AD-26672	5253	5912	483	1142	1396
  AD-26673	5254	5913	484	1143	1397
  AD-26674	5255	5914	485	1144	1410
  AD-26675	5256	5915	486	1145	1411
  AD-26676	5257	5916	487	1146	1414
  AD-26677	5258	5917	488	1147	2371
  AD-26678	5259	5918	489	1148	1415
  AD-26679	5260	5919	490	1149	1420
  AD-26680	5261	5920	491	1150	1427
  AD-26681	5262	5921	492	1151	1430
  AD-26682	5263	5922	493	1152	1432
  AD-26683	5264	5923	494	1153	1438
  AD-26684	5265	5924	495	1154	1447
  AD-26685	5266	5925	496	1155	1456
  AD-26686	5267	5926	497	1156	1465
  AD-26687	5268	5927	498	1157	1468
  AD-26688	5269	5928	499	1158	1474
  AD-26689	5270	5929	500	1159	1481
  AD-26690	5271	5930	501	1160	1486
  AD-26691	5272	5931	502	1161	1489
  AD-26692	5273	5932	503	1162	1490
  AD-26693	5274	5933	504	1163	2441
  AD-26694	5275	5934	505	1164	1491
  AD-26695	5276	5935	506	1165	1493
  AD-26696	5277	5936	507	1166	1494
  AD-26697	5278	5937	508	1167	1517
  AD-26698	5279	5938	509	1168	1518
  AD-26699	5280	5939	510	1169	1519
  AD-26700	5281	5940	511	1170	1522
  AD-26701	5282	5941	512	1171	1523
  AD-26702	5283	5942	513	1172	1526
  AD-26703	5284	5943	514	1173	1527
  AD-26704	5285	5944	515	1174	1539
  AD-26705	5286	5945	516	1175	1540
  AD-26706	5287	5946	517	1176	1545
  AD-26707	5288	5947	518	1177	1546
  AD-26708	5289	5948	519	1178	1547
  AD-26709	5290	5949	520	1179	1580
  AD-26710	5291	5950	521	1180	1581
  AD-26711	5292	5951	522	1181	1591
  AD-26712	5293	5952	523	1182	1598
  AD-26713	5294	5953	524	1183	1606
  AD-26714	5295	5954	525	1184	1629
  AD-26715	5296	5955	526	1185	1644
  AD-26716	5297	5956	527	1186	1654
  AD-26717	5298	5957	528	1187	1678
  AD-26718	5299	5958	529	1188	1681
  AD-26719	5300	5959	530	1189	1689
  AD-26720	5301	5960	531	1190	1699
  AD-26721	5302	5961	532	1191	1705
  AD-26722	5303	5962	533	1192	1711
  AD-26723	5304	5963	534	1193	1716
  AD-26724	5305	5964	535	1194	1717
  AD-26725	5306	5965	536	1195	1723
  AD-26726	5307	5966	537	1196	1729
  AD-26727	5308	5967	538	1197	1735
  AD-26728	5309	5968	539	1198	1736
  AD-26729	5310	5969	540	1199	1737
  AD-26730	5311	5970	541	1200	1743
  AD-26731	5312	5971	542	1201	1744
  AD-26732	5313	5972	543	1202	1754
  AD-26733	5314	5973	544	1203	1770
  AD-26734	5315	5974	545	1204	1771
  AD-26735	5316	5975	546	1205	1772
  AD-26736	5317	5976	547	1206	1778
  AD-26737	5318	5977	548	1207	1783
  AD-26738	5319	5978	549	1208	1787
  AD-26739	5320	5979	550	1209	1792
  AD-26740	5321	5980	551	1210	1798
  AD-26741	5322	5981	552	1211	1861
  AD-26742	5323	5982	553	1212	1866
  AD-26743	5324	5983	554	1213	1870
  AD-26744	5325	5984	555	1214	1873
  AD-26745	5326	5985	556	1215	1882
  AD-26746	5327	5986	557	1216	1888
  AD-26747	5328	5987	558	1217	1889
  AD-26748	5329	5988	559	1218	1928
  AD-26749	5330	5989	560	1219	1929
  AD-26750	5331	5990	561	1220	1930
  AD-26751	5332	5991	562	1221	1955
  AD-26752	5333	5992	563	1222	1956
  AD-26753	5334	5993	564	1223	1999
  AD-26754	5335	5994	565	1224	2002
  AD-26755	5336	5995	566	1225	2007
  AD-26756	5337	5996	567	1226	2013
  AD-26757	5338	5997	568	1227	2014
  AD-26758	5339	5998	569	1228	2038
  AD-26759	5340	5999	570	1229	2042
  AD-26760	5341	6000	571	1230	2046
  AD-26761	5342	6001	572	1231	2047
  AD-26762	5343	6002	573	1232	2059
  AD-26763	5344	6003	574	1233	2060
  AD-26764	5345	6004	575	1234	2061
  AD-26765	5346	6005	576	1235	2062
  AD-26766	5347	6006	577	1236	2063
  AD-26767	5348	6007	578	1237	2070
  AD-26768	5349	6008	579	1238	2071
  AD-26769	5350	6009	580	1239	2076
  AD-26770	5351	6010	581	1240	2079
  AD-26771	5352	6011	582	1241	2083
  AD-26772	5353	6012	583	1242	2110
  AD-26773	5354	6013	584	1243	2128
  AD-26774	5355	6014	585	1244	2178
  AD-26775	5356	6015	586	1245	2179
  AD-26776	5357	6016	587	1246	2182
  AD-26777	5358	6017	588	1247	2189
  AD-26778	5359	6018	589	1248	2193
  AD-26779	5360	6019	590	1249	2194
  AD-26780	5361	6020	591	1250	2197
  AD-26781	5362	6021	592	1251	2234
  AD-26782	5363	6022	593	1252	2235
  AD-26783	5364	6023	594	1253	2254
  AD-26784	5365	6024	595	1254	2257
  AD-26785	5366	6025	596	1255	2262
  AD-26786	5367	6026	597	1256	2265
  AD-26787	5368	6027	598	1257	2272
  AD-26788	5369	6028	599	1258	2278
  AD-26789	5370	6029	600	1259	2298
  AD-26790	5371	6030	601	1260	2303
  AD-26791	5372	6031	602	1261	2365
  AD-26792	5373	6032	603	1262	2375
  AD-26793	5374	6033	604	1263	2376
  AD-26794	5375	6034	605	1264	2386
  AD-26795	5376	6035	606	1265	2393
  AD-26796	5377	6036	607	1266	2397
  AD-26797	5378	6037	608	1267	2398
  AD-26798	5379	6038	609	1268	2402
  AD-26799	5380	6039	610	1269	2406
  AD-26800	5381	6040	611	1270	2407
  AD-26801	5382	6041	612	1271	2420
  AD-26802	5383	6042	613	1272	2421
  AD-26803	5384	6043	614	1273	2422
  AD-26804	5385	6044	615	1274	2431
  AD-26805	5386	6045	616	1275	2436
  AD-26806	5387	6046	617	1276	2451
  AD-26807	5388	6047	618	1277	2454
  AD-26808	5389	6048	619	1278	675
  AD-26809	5390	6049	620	1279	676
  AD-26810	5391	6050	621	1280	679
  AD-26811	5392	6051	622	1281	2458
  AD-26812	5393	6052	623	1282	2461
  AD-26813	5394	6053	624	1283	2466
  AD-26814	5395	6054	625	1284	2493
  AD-26815	5396	6055	626	1285	2494
  AD-26816	5397	6056	627	1286	2503
  AD-26817	5398	6057	628	1287	2515
  AD-26818	5399	6058	629	1288	2542
  AD-26819	5400	6059	630	1289	2580
  AD-26820	5401	6060	631	1290	2581
  AD-26821	5402	6061	632	1291	2595
  AD-26822	5403	6062	633	1292	2601
  AD-26823	5404	6063	634	1293	2605
  AD-26824	5405	6064	635	1294	2606
  AD-26825	5406	6065	636	1295	2607
  AD-26826	5407	6066	637	1296	878
  AD-26900	5408	6067	638	1297	2745
  AD-26901	5409	6068	639	1298	2872
  AD-26902	5410	6069	640	1299	2915
  AD-26903	5411	6070	641	1300	2916
  AD-26904	5412	6071	642	1301	2918
  AD-26905	5413	6072	643	1302	2919
  AD-26906	5414	6073	644	1303	2939
  AD-26907	5415	6074	645	1304	2978
  AD-26908	5416	6075	646	1305	2979
  AD-26909	5417	6076	647	1306	2980
  AD-26910	5418	6077	648	1307	2981
  AD-26911	5419	6078	649	1308	2983
  AD-26912	5420	6079	650	1309	2984
  AD-26913	5421	6080	651	1310	2986
  AD-26914	5422	6081	652	1311	3081
  AD-26915	5423	6082	653	1312	3082
  AD-26916	5424	6083	654	1313	2917
  AD-26917	5425	6084	655	1314	2994
  AD-26918	5426	6085	656	1315	2995
  AD-26919	5427	6086	657	1316	3134
  AD-26920	5428	6087	658	1317	1535
  AD-26921	5429	6088	659	1318	1801
  SET1 1245	6090	6111	6193	6361	1227
  SET1 1245	6090	6111	6214	6382	1227
  SET1 1245	6090	6111	6151	6319	1227
  SET1 1245	6090	6111	6172	6340	1227
  SET1 1249	6091	6112	6199	6367	1231
  SET1 1249	6091	6112	6220	6388	1231
  SET1 1249	6091	6112	6157	6325	1231
  SET1 1249	6091	6112	6178	6346	1231
  SET1 1250	6092	6113	6200	6368	1232
  SET1 1250	6092	6113	6221	6389	1232
  SET1 1250	6092	6113	6158	6326	1232
  SET1 1250	6092	6113	6179	6347	1232
  SET1 1450	6093	6114	6195	6363	1432
  SET1 1450	6093	6114	6216	6384	1432
  SET1 1450	6093	6114	6153	6321	1432
  SET1 1450	6093	6114	6174	6342	1432
  SET1 1545	6094	6115	6202	6370	1527
  SET1 1545	6094	6115	6223	6391	1527
  SET1 1545	6094	6115	6160	6328	1527
  SET1 1545	6094	6115	6181	6349	1527
  SET1 1755	6095	6116	6203	6371	1737
  SET1 1755	6095	6116	6224	6392	1737
  SET1 1755	6095	6116	6161	6329	1737
  SET1 1755	6095	6116	6182	6350	1737
  SET1 1814	6096	6117	6192	6360	1796
  SET1 1814	6096	6117	6213	6381	1796
  SET1 1814	6096	6117	6150	6318	1796
  SET1 1814	6096	6117	6171	6339	1796
  SET1 1816	6097	6118	6187	6355	1798
  SET1 1816	6097	6118	6208	6376	1798
  SET1 1816	6097	6118	6145	6313	1798
  SET1 1816	6097	6118	6166	6334	1798
  SET1 1974	6098	6119	6188	6356	1956
  SET1 1974	6098	6119	6209	6377	1956
  SET1 1974	6098	6119	6146	6314	1956
  SET1 1974	6098	6119	6167	6335	1956
  SET1 2202	6099	6120	6201	6369	2184
  SET1 2202	6099	6120	6222	6390	2184
  SET1 2202	6099	6120	6159	6327	2184
  SET1 2202	6099	6120	6180	6348	2184
  SET1 2425	6100	6121	6189	6357	2407
  SET1 2425	6100	6121	6210	6378	2407
  SET1 2425	6100	6121	6147	6315	2407
  SET1 2425	6100	6121	6168	6336	2407
  SET1 254	6101	6122	6183	6351	236
  SET1 254	6101	6122	6204	6372	236
  SET1 254	6101	6122	6141	6309	236
  SET1 254	6101	6122	6162	6330	236
  SET1 3146	6102	6123	6190	6358	3128
  SET1 3146	6102	6123	6211	6379	3128
  SET1 3146	6102	6123	6148	6316	3128
  SET1 3146	6102	6123	6169	6337	3128
  SET1 3169	6103	6124	6196	6364	3151
  SET1 3169	6103	6124	6217	6385	3151
  SET1 3169	6103	6124	6154	6322	3151
  SET1 3169	6103	6124	6175	6343	3151
  SET1 3196	6104	6125	6194	6362	3178
  SET1 3196	6104	6125	6215	6383	3178
  SET1 3196	6104	6125	6152	6320	3178
  SET1 3196	6104	6125	6173	6341	3178
  SET1 3477	6105	6126	6197	6365	3459
  SET1 3477	6105	6126	6218	6386	3459
  SET1 3477	6105	6126	6155	6323	3459
  SET1 3477	6105	6126	6176	6344	3459
  SET1 703	6106	6127	6184	6352	685
  SET1 703	6106	6127	6205	6373	685
  SET1 703	6106	6127	6142	6310	685
  SET1 703	6106	6127	6163	6331	685
  SET1 709	6107	6128	6185	6353	691
  SET1 709	6107	6128	6206	6374	691
  SET1 709	6107	6128	6143	6311	691
  SET1 709	6107	6128	6164	6332	691
  SET1 865	6108	6129	6198	6366	847
  SET1 865	6108	6129	6219	6387	847
  SET1 865	6108	6129	6156	6324	847
  SET1 865	6108	6129	6177	6345	847
  SET1 889	6109	6130	6191	6359	871
  SET1 889	6109	6130	6212	6380	871
  SET1 889	6109	6130	6149	6317	871
  SET1 889	6109	6130	6170	6338	871
  SET1 895	6110	6131	6186	6354	877
  SET1 895	6110	6131	6207	6375	877
  SET1 895	6110	6131	6144	6312	877
  SET1 895	6110	6131	6165	6333	877
  SET1 1245	6090	6111	6235	6403	1227
  SET1 1245	6090	6111	6256	6424	1227
  SET1 1245	6090	6111	6277	6445	1227
  SET1 1245	6090	6111	6298	6466	1227
  SET1 1249	6091	6112	6241	6409	1231
  SET1 1249	6091	6112	6262	6430	1231
  SET1 1249	6091	6112	6283	6451	1231
  SET1 1249	6091	6112	6304	6472	1231
  SET1 1250	6092	6113	6242	6410	1232
  SET1 1250	6092	6113	6263	6431	1232
  SET1 1250	6092	6113	6284	6452	1232
  SET1 1250	6092	6113	6305	6473	1232
  SET1 1450	6093	6114	6237	6405	1432
  SET1 1450	6093	6114	6258	6426	1432
  SET1 1450	6093	6114	6279	6447	1432
  SET1 1450	6093	6114	6300	6468	1432
  SET1 1545	6094	6115	6244	6412	1527
  SET1 1545	6094	6115	6265	6433	1527
  SET1 1545	6094	6115	6286	6454	1527
  SET1 1545	6094	6115	6307	6475	1527
  SET1 1755	6095	6116	6245	6413	1737
  SET1 1755	6095	6116	6266	6434	1737
  SET1 1755	6095	6116	6287	6455	1737
  SET1 1755	6095	6116	6308	6476	1737
  SET1 1814	6096	6117	6234	6402	1796
  SET1 1814	6096	6117	6255	6423	1796
  SET1 1814	6096	6117	6276	6444	1796
  SET1 1814	6096	6117	6297	6465	1796
  SET1 1816	6097	6118	6229	6397	1798
  SET1 1816	6097	6118	6250	6418	1798
  SET1 1816	6097	6118	6271	6439	1798
  SET1 1816	6097	6118	6292	6460	1798
  SET1 1974	6098	6119	6230	6398	1956
  SET1 1974	6098	6119	6251	6419	1956
  SET1 1974	6098	6119	6272	6440	1956
  SET1 1974	6098	6119	6293	6461	1956
  SET1 2202	6099	6120	6243	6411	2184
  SET1 2202	6099	6120	6264	6432	2184
  SET1 2202	6099	6120	6285	6453	2184
  SET1 2202	6099	6120	6306	6474	2184
  SET1 2425	6100	6121	6231	6399	2407
  SET1 2425	6100	6121	6252	6420	2407
  SET1 2425	6100	6121	6273	6441	2407
  SET1 2425	6100	6121	6294	6462	2407
  SET1 254	6101	6122	6225	6393	236
  SET1 254	6101	6122	6246	6414	236
  SET1 254	6101	6122	6267	6435	236
  SET1 254	6101	6122	6288	6456	236
  SET1 3146	6102	6123	6232	6400	3128
  SET1 3146	6102	6123	6253	6421	3128
  SET1 3146	6102	6123	6274	6442	3128
  SET1 3146	6102	6123	6295	6463	3128
  SET1 3169	6103	6124	6238	6406	3151
  SET1 3169	6103	6124	6259	6427	3151
  SET1 3169	6103	6124	6280	6448	3151
  SET1 3169	6103	6124	6301	6469	3151
  SET1 3196	6104	6125	6236	6404	3178
  SET1 3196	6104	6125	6257	6425	3178
  SET1 3196	6104	6125	6278	6446	3178
  SET1 3196	6104	6125	6299	6467	3178
  SET1 3477	6105	6126	6239	6407	3459
  SET1 3477	6105	6126	6260	6428	3459
  SET1 3477	6105	6126	6281	6449	3459
  SET1 3477	6105	6126	6302	6470	3459
  SET1 703	6106	6127	6226	6394	685
  SET1 703	6106	6127	6247	6415	685
  SET1 703	6106	6127	6268	6436	685
  SET1 703	6106	6127	6289	6457	685
  SET1 709	6107	6128	6227	6395	691
  SET1 709	6107	6128	6248	6416	691
  SET1 709	6107	6128	6269	6437	691
  SET1 709	6107	6128	6290	6458	691
  SET1 865	6108	6129	6240	6408	847
  SET1 865	6108	6129	6261	6429	847
  SET1 865	6108	6129	6282	6450	847
  SET1 865	6108	6129	6303	6471	847
  SET1 889	6109	6130	6233	6401	871
  SET1 889	6109	6130	6254	6422	871
  SET1 889	6109	6130	6275	6443	871
  SET1 889	6109	6130	6296	6464	871
  SET1 895	6110	6131	6228	6396	877
  SET1 895	6110	6131	6249	6417	877
  SET1 895	6110	6131	6270	6438	877
  SET1 895	6110	6131	6291	6459	877

Various Embodiments of the Present Disclosure
• Various RNAi agents to Beta-Catenin are disclosed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• Tables 1, 2 and 3 provide the sequence, SEQ ID NOs and positions of various RNAi agents to Beta-Catenin, including both unmodified sequences and example modified sequences. The sequences in Table 2 are not modified.
• Table 3 provides the sequences and SEQ ID NOs for example modified sequences of the sense and anti-sense strands of various RNAi agents to Beta-Catenin. The present disclosure also encompasses unmodified versions of these sequences, and different versions comprising other modifications or patterns of modification (but the same sequence of bases).
• In the sequences in Table 3, lower-case letters (e.g., c, u) indicate modified nucleotides while upper case letters (e.g., C, U, A, G) indicate unmodified nucleotides. In Table 3, example modified versions of each of the sequences are shown. However, the present disclosure encompasses unmodified versions of these sequences and other versions which comprise additional or alternative modifications. Thus, for example, AD-18892 can optionally have the unmodified (or “generic”) sequence UGGUGCUGACUAUCCAGUU (SEQ ID NO: 429) in the sense strand and AACUGGAUAGUCAGCACCA (SEQ ID NO: 430) in the anti-sense strand. The present disclosure also encompasses alternative modified versions of the duplex comprising UGGUGCUGACUAUCCAGUU (SEQ ID NO: 429) in the sense strand and AACUGGAUAGUCAGCACCA (SEQ ID NO: 430) in the anti-sense strand.
• In the sequences in Tables 1, 2, 3, 4, 5, 6, 7 and 8, the modified and unmodified sequences can optionally comprise the sequence “dTdT”, “dTsdT” or “UU” at the 3′ end. Thus, for example, AD-18892 can optionally have the modified sequence uGGuGcuGAcuAuccAGuudTdT (SEQ ID NO: 6136) or uGGuGcuGAcuAuccAGuudTsdT (SEQ ID NO: 6137) in the sense strand; and AACUGGAuAGUcAGcACcAdTdT (SEQ ID NO: 6138) or AACUGGAuAGUcAGcACcAdTsdT (SEQ ID NO: 6139) in the anti-sense strand. As noted in Table 3, below, dT is 2′-deoxy-thymidine-5′-phosphate and sdT is 2′-deoxy Thymidine 5′-phosphorothioate. In the disclosed sequences, terminal dinucleotide “UU” is 2′-OMe-U 2′-OMe-U, and neither the terminal TT nor the terminal UU are in the inverted/reverse orientation. In various embodiments UU as standard RNA can also be used.
• The terminal dithymidine (or TT or dTdT or sdTsdT or UU or the like) is not part of the Beta-Catenin target sequence, but is a modified variant of the dithymidine dinucleotide commonly placed as an overhang to protect the ends of siRNAs from nucleases (see, for example, Elbashir et al. 2001 Nature 411: 494-498; Elbashir et al. 2001 EMBO J. 20: 6877-6888; and Kraynack et al. 2006 RNA 12:163-176). A terminal dinucleotide is known from these references to enhance nuclease resistance but not contribute to target recognition. On any modified or unmodified sequence, a 3′ end cap, as is known in the art, can be used instead of a terminal dinucleotide to stabilize the end from nuclease degradation provided that the 3′ end cap is able to both stabilize the RNAi agent (e.g., against nucleases) and not interfere excessively with siRNA activity.
• Table 4 provides sets of overlapping RNAi agents to Beta-Catenin.
• Activity levels of various Beta-Catenin RNAi agents are provided in Tables 5 to 9.
• RNAi Agent Comprising an Anti-Sense Strand of a RNAi Agent Described Herein
• In one particular specific embodiment, the present disclosure relates to a composition comprising a RNAi agent for inhibition of the target gene Beta-Catenin comprising an anti-sense strand, wherein the anti-sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the anti-sense strand of a RNAi agent to Beta-Catenin selected from those anti-sense strands in the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• In one embodiment, the composition comprises a RNAi agent for inhibition of the target gene Beta-Catenin comprising a sense and an anti-sense strand, wherein the sequence of the sense strand and the sequence of the anti-sense strand are the sequences of the sense and anti-sense strand, respectively, of any RNAi agent provided herein. In one embodiment, the composition comprises a RNAi agent for inhibition of the target gene Beta-Catenin comprising a sense and an anti-sense strand, wherein the sequence of the antisense strand is the sequence of anti-sense strand of any RNAi agent provided herein. In one embodiment, the composition comprises a RNAi agent for inhibition of the target gene Beta-Catenin comprising a sense and an anti-sense strand, wherein the sequence of the sense strand and the sequence of the anti-sense strand are the sequences of the sense and anti-sense strand, respectively, of any RNAi agent provided herein, further comprising an additional about 6 to 20 nucleotides on one or both strands (e.g., about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 nt). In one embodiment, the composition comprises a RNAi agent for inhibition of the target gene Beta-Catenin comprising a sense and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of any RNAi agent provided herein, further comprising an additional about 6 to 20 nucleotides on one or both strands (e.g., about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 nt). In these various embodiments, the RNAi agent is for inhibition of the target gene Beta-Catenin.
• Various specific embodiments of these embodiments are described below.
• In one embodiment, the composition further comprises a second RNAi agent to Beta-Catenin. In various embodiments, the second RNAi agent is physically separate from the first, or the two are physically connected (e.g., covalently linked or otherwise conjugated), or combined within the same pharmaceutical composition.
• In one embodiment, the antisense strand is about 30 or fewer nt in length.
• In one embodiment, the sense strand and the antisense strand form a duplex region of about 15 to about 30 nucleotide pairs in length.
• In one embodiment, the antisense strand is about 15 to about 36 nt in length, about 17 to about 30 nt in length, about 17 to 23 nt in length, about 19 to about 49 nt in length, or about 19 to about 23 nt in length. In one embodiment, the antisense strand has at least the length selected from about 15 nt, about 16 nt, about 17 nt, about 18 nt, about 19 nt, about 20 nt, about 21 nt, about 22 nt, about 23 nt, about 24 nt, about 25 nt, about 26 nt, about 27 nt, about 28 nt, about 29 nt and about 30 nt.
• In one embodiment, the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment, e.g., blood serum or intestinal lavage fluid.
• In one embodiment, the RNAi agent comprises at least one sugar backbone modification (e.g., phosphorothioate linkage) and/or at least one 2′-modified nucleotide. In one embodiment, all the pyrimidines are 2′ O-methyl-modified nucleotides.
• In one embodiment, the RNAi agent comprises: at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide; and/or at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide; and/or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• In one embodiment, the RNAi agent comprises a 2′-modification selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA). In one embodiment, all the pyrimidines are 2′ O-methyl-modified nucleotides.
• In one embodiment, the RNAi agent comprises a blunt end.
• In one embodiment, the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• In one embodiment, the RNAi agent comprises an overhang at the 3′-end of the antisense strand of the RNAi agent.
• In one embodiment, the RNAi agent is ligated to one or more diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 60% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 70% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 80% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 90% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi has an EC50 of no more than about 0.1 nM.
• In one embodiment, the RNAi has an EC50 of no more than about 0.01 nM.
• In one embodiment, the RNAi has an EC50 of no more than about 0.001 nM.
• A RNAi Agent Comprising a First and a Second Strand
• In one particular specific embodiment, the present disclosure relates to a composition comprising a RNAi agent for inhibition of the target gene Beta-Catenin comprising a first strand and a second strand, wherein the first strand and second strand comprise at least 15 contiguous nucleotides, each differing by 0, 1, 2, or 3 nucleotides from the first and second strand, respectively, of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In these various embodiments, the RNAi agent is for inhibition of the target gene Beta-Catenin.
• Various specific embodiments of this embodiment are described below.
• In one embodiment, the composition further comprises a second RNAi agent to Beta-Catenin. In various embodiments, the second RNAi agent is physically separate from the first, or the two are physically connected (e.g., covalently linked or otherwise conjugated), or combined within the same pharmaceutical composition.
• In one embodiment, the antisense strand is about 30 or fewer nt in length.
• In one embodiment, the sense strand and the antisense strand form a duplex region of about 15 to about 30 nt pairs in length.
• In one embodiment, the antisense strand is about 15 to about 36 nt in length, including about 17 to about 23 nt in length, and including about 19 to about 23 nt in length. In one embodiment, the antisense strand has at least the length selected from about 15 nt, about 16 nt, about 17 nt, about 18 nt, about 19 nt, about 20 nt, about 21 nt, about 22 nt, about 23 nt, about 24 nt, about 25 nt, about 26 nt, about 27 nt, about 28 nt, about 29 nt and about 30 nt.
• In one embodiment, the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment, e.g., blood serum or intestinal lavage fluid.
• In one embodiment, the RNAi agent comprises at least one sugar backbone modification (e.g., phosphorothioate linkage) and/or at least one 2′-modified nucleotide. In one embodiment, all the pyrimidines are 2′ O-methyl-modified nucleotides.
• In one embodiment, the RNAi agent comprises: at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide; and/or at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide; and/or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• In one embodiment, the RNAi agent comprises a 2′-modification selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• In one embodiment, the RNAi agent comprises a blunt end.
• In one embodiment, the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• In one embodiment, the RNAi agent comprises an overhang at the 3′-end of the antisense strand of the RNAi agent.
• In one embodiment, the RNAi agent is ligated to one or more diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 60% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 70% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 80% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 90% at a concentration of 10 nM in HeLa cells in vitro.
• In one embodiment, the RNAi has an EC50 of no more than about 0.1 nM.
• In one embodiment, the RNAi has an EC50 of no more than about 0.01 nM.
• In one embodiment, the RNAi has an EC50 of no more than about 0.001 nM.
• A Method of Treatment Using a RNAi Agent Described Herein
• In one particular specific embodiment, the present disclosure relates to a method of treating a Beta-Catenin-related disease in an individual, comprising the step of administering to the individual a therapeutically effective amount of a composition comprising any one or more of the RNAi agents disclosed herein. In one embodiment of this method, the RNAi agent comprises at least an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises a sense and an anti-sense strand, wherein the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sense strand of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the first strand of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand comprises the sequence of the first strand of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand is the sequence of the first strand of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In these various embodiments, the RNAi agent is for the inhibition of the target gene Beta-Catenin.
• Various particular specific embodiments of these embodiments are described below.
• In one embodiment, the Beta-Catenin-related disease is adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and/or impaired wound healing, and/or similar and related diseases.
• In one embodiment, the Beta-Catenin-related disease is cancer.
• In one embodiment, the method further comprises the administration of an additional treatment. In one embodiment, the additional treatment is a therapeutically effective amount of a composition.
• In one embodiment, the additional treatment is a method (or procedure).
• In one embodiment, the additional treatment and the RNAi agent can be administered in any order, or can be administered simultaneously.
• In one embodiment, the method further comprises the step of administering an additional treatment for adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and/or impaired wound healing, and/or similar and related diseases.
• In one embodiment, the composition comprises a second RNAi agent to Beta-Catenin. In various embodiments, the second RNAi agent is physically separate from the first, or the two are physically connected (e.g., covalently linked or otherwise conjugated), or combined within the same pharmaceutical composition.
• In one embodiment, the method further comprises the step of administering an additional RNAi agent which comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• Inhibiting the Expression of Beta-Catenin, Using a RNAi Agent
• In one particular specific embodiment, the present disclosure relates to a method of inhibiting the expression of the Beta-Catenin gene in an individual, comprising the step of administering to the individual a therapeutically effective amount of a composition comprising any one or more of the RNAi agents of the present disclosure. In one embodiment, the RNAi agent comprises at least an anti-sense strand, and/or comprises a sense and an anti-sense strand, wherein the anti-sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the anti-sense strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises a sense and an anti-sense strand, wherein the anti-sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the anti-sense strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand comprises sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand is sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• Various embodiments of this aspect of these embodiments are described below.
• In one embodiment, the individual is afflicted with or susceptible to a Beta-Catenin-related disease.
• In one embodiment, the Beta-Catenin-related disease is adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and/or impaired wound healing, and/or similar and related diseases.
• In one embodiment, the Beta-Catenin-related disease is cancer.
• In one embodiment, the method further comprises the administration of an additional treatment. In one embodiment, the additional treatment is a therapeutically effective amount of a composition.
• In one embodiment, the additional treatment is a method (or procedure).
• In one embodiment, the additional treatment and the RNAi agent can be administered in any order or can be administered simultaneously.
• In one embodiment, the method further comprises the step of administering an additional treatment for adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and/or impaired wound healing, and/or similar and related diseases.
• In one embodiment, the composition comprises a second RNAi agent to Beta-Catenin. In various embodiments, the second RNAi agent is physically separate from the first, or the two are physically connected (e.g., covalently linked or otherwise conjugated), or combined within the same pharmaceutical composition.
• In one embodiment, the method further comprises the step of administering an additional RNAi agent which comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent to Beta-Catenin selected from the specific duplexes provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• Pharmaceutical Formulations of a RNAi Agent to Beta-Catenin
• In one particular specific embodiment, the present disclosure relates to a composition comprising any one or more of the RNAi agents of the present disclosure. In one embodiment, the RNAi agent comprises at least an anti-sense strand, and/or comprises a sense and an anti-sense strand, wherein the anti-sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the anti-sense strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand comprises the sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand is the sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation.
• In one embodiment, the present disclosure pertains to the use of a RNAi agent in the manufacture of a medicament for treatment of a Beta-Catenin-related disease, wherein the RNAi agent is any RNAi disclosed herein. In one embodiment, the RNAi agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the RNAi agent comprises at least an anti-sense strand, and/or comprises a sense and an anti-sense strand, wherein the anti-sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the anti-sense strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand comprises the sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation. In one embodiment, the RNAi agent comprises a first and a second strand, wherein the sequence of the first strand is the sequence of the first strand of a RNAi agent to Beta-Catenin selected from those specific duplex provided herein and as listed, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, wherein the composition is in a pharmaceutically effective formulation.
• Specific Embodiments of RNAi Agents to Beta-Catenin Comprising Mismatches from the Disclosed Sequences
• Various specific embodiments of a RNAi agent to Beta-Catenin are disclosed herein. The present disclosure encompasses the example modified sequences provided in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and the corresponding unmodified sequences and other modified sequences (e.g., modified and unmodified variants). Specific embodiments of the present disclosure include RNAi agents which comprise sequences differing by 0, 1, 2, or 3 nt (nucleotides) or bp [basepair(s)] (e.g., with 0, 1, 2 or 3 mismatches) from any of the RNAi agents listed in Table 1, and modified and unmodified variants thereof. As described in additional detail below, a mismatch is defined herein as a difference between the base sequence (e.g., A instead of G) or length when two sequences are maximally aligned and compared. In addition, as described in more detail below, an “unmodified variant” is a variant in which the base sequence is identical, but none of the bases are modified; this includes, for example, the corresponding portion of the wild-type Beta-Catenin mRNA or gene. A “modified variant” contains one or more modifications (or one or more fewer or different modifications) to a nucleotide, sugar, phosphate or backbone, and/or addition of one or more moieties; but without a change, substitution, addition, or deletion to the base sequence. A particular sequence and its modified or unmodified variants have 0 mismatches among them.
• In one particular embodiment, the present disclosure comprises a RNAi agent comprising a anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand of: any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In another particular embodiment, the RNAi agent comprises a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sense strand of any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
Definitions
• For convenience, the meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in other parts of this specification and its definition provided in this section, the definition in this section shall prevail.
Other Embodiments
• Various particular specific embodiments of this disclosure are described below.
• In one embodiment, the disclosure pertains to a composition according to any of the disclosed embodiments, for use in a method of treating a Beta-Catenin-related disease in an individual, the method comprising the step of administering to the individual a therapeutically effective amount of a composition according to the disclosure.
• Various particular specific embodiments of this embodiment are described below.
• In one embodiment, the disclosure pertains to the composition according to any of the above embodiments, for use in a method of inhibiting the expression of Beta-Catenin in an individual, the method comprising the step of administering to the individual a therapeutically effective amount of a composition according to any of the disclosed embodiments.
• One embodiment of the disclosure is the use of a composition according to any of the above embodiments, in the manufacture of a medicament for treatment of an Beta-Catenin-related disease.
• In one embodiment, the Beta-Catenin-related disease is selected from cancer, viral disease or autoimmune disease.
• In one embodiment, the disclosure pertains to the composition of any of the above embodiments, for use in the treatment of an Beta-Catenin-related disease.
• In one embodiment, the Beta-Catenin-related disease is selected from cancer, viral disease or autoimmune disease.
• In one embodiment, the disclosure relates to a method of inhibiting the expression of Beta-Catenin in an cell, comprising the step of introducing into the cell a composition comprising an RNAi agent comprising an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of an RNAi agent to Beta-Catenin selected from the Beta-Catenin siRNAs disclosed herein.
• In one embodiment, the disclosure relates to a method of inhibiting the expression of Beta-Catenin in an cell, comprising the step of introducing into the cell a composition comprising an RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand, and the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sense strand of an RNAi agent to Beta-Catenin selected from the Beta-Catenin siRNAs disclosed herein.
• Beta-Catenin
• By “Beta-Catenin” is meant the gene, mRNA, and/or protein, or any nucleic acid encoding the protein, also designated cadherin-associated protein beta 1; CTNNB1; CTNNB; CTNNB; CTNB1; FLJ25606; OMIM: 116806; MGI: 88276 HomoloGene: 1434; OTTHUMP00000209288; DKFZp686D02253; HGNC: 2514; Entrez Gene: 1499; Ensembl: ENSG00000168036; UniProtKB: P35222; GC03P040551; GC03P041054; or GC03P041201. See: Kraus et al. 1994. Genomics 23: 272-4.
• Beta-Catenin is involved in the regulation of cell adhesion and in signal transduction through the Wnt pathway. It is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers and regulate cell growth and adhesion between cells. Beta-Catenin also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete.
• When Beta-Catenin was sequenced, it was found to be a member of the armadillo family of proteins. These proteins have multiple copies of the so-called armadillo repeat domain, which is specialized for protein-protein binding. When Beta-Catenin is not associated with cadherins and alpha-catenin, it can interact with other proteins such as ICAT and APC.
• Beta-Catenin is also involved in the Wnt pathway. When Wnt is not present, GSK-3 (a kinase) constitutively phosphorylates the Beta-Catenin protein. Beta-Catenin is associated with axin (scaffolding protein) complexed with GSK-3 and APC (adenomatosis polyposis coli). The creation of this complex increases the phosphorylation of Beta-Catenin by facilitating the activity of GSK-3. When Beta-Catenin is phosphorylated, it is degraded and thus does not significantly accumulate in the cell. When Wnt binds to frizzled (Fz), its receptor, dishevelled (Dsh), is recruited to the membrane. GSK-3 is inhibited by the activation of Dsh by Fz. Because of this, Beta-Catenin is permitted to accumulate in the cytosol and can be translocated to the nucleus, where it performs several functions. It can act in conjunction with TCF/LEF transcription factors to activate target genes involved in different processes, including proliferation, survival and matrix remodeling.
• Beta-Catenin interacts with many other proteins, including: cadherins, transcription factors, axin, galectin-3, beta-galactoside-binding protein, GSK-3, protein kinase A, Androgen receptor, APC, AXIN1, CBY1, CDH1, CDH2, CDH3, CDK5R1, CHUK, CTNNA1, CTNND1, EGFR, FHL2, HER2/neu, HNF4A, IKK2, LEF1, MAGI1, MUC1, NF5A1, PCAF, PHF17, Plakoglobin, PTPN14, PTPRF, PRPRK, PSEN1, RuvB-like 1, SMAD7, SLC913R1, SMARCA4, USP9X, and VE-cadherin.
• Beta-Catenin is associated with several diseases. Beta-Catenin itself can act as an oncogene. In adenomatous polyposis of the colon, the APC gene, whose product binds Beta-Catenin, is mutated. As described in more detail below, mutations in, over-expression of, and/or abnormal cellular compartmentalization (e.g., aberrant accumulation in the cytoplasm and/or nucleus) of Beta-Catenin are associated with various diseases, including: adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, pilomatrixoma, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, anaplastic thyroid carcinoma, and uterine carcinosarcoma. See: Thompson et al. 2007 Hepatology 45: 1298-305; Wang et al. 2008 Cancer Epidemiol. Biomarkers Prev. 17: 2101-8; Saldanha et al. Br. J. Dermatol. 151: 157-64.
• Nuclear and cytosolic accumulation (e.g., improper cellular compartmentalization) is enriched in basal-like breast cancer and are associated with poor outcome. Beta-Catenin accumulation is more often observed in basal-like in situ carcinomas than in other sub-types, suggesting that activation of this pathway might be an early event in basal-like tumor development. Khramtsov et al. 2010 Am. J. Pathol. 176: 2911-2920.
• Sequences and Structure of Beta-Catenin
• Three human transcript variants encoding the same protein have been found for this gene: NP_001091679.1; NP_001091680.1; and NP_001895.1. The amino acid and nucleotide sequences of human Beta-Catenin are provided in LOCUS NM_001098209 (ACCESSION NM_001098209 XM_001133660 XM_001133664 XM_001133673 XM_001133675; VERSION NM_001098209.1 GI:148233337); LOCUS NM_001098210 (ACCESSION NM_001098210; VERSION NM_001098210.1 GI:148227671); and LOCUS NM_001904 (ACCESSION NM_001904 XM_942045 XM_945648 XM_945650 XM_945651 XM_945652 XM_945653 XM_945654 XM_945655 XM_945657; VERSION NM_001904.3 GI:148228165).
• The mouse (Mus musculus) sequence of Beta-Catenin is available as Q02248 (CTNB1_MOUSE); MGI:88276; NP_031640.1 GI:6671684; NM_007614.3. The rat (Rattus norvegicus) sequence is available as Q9WU82 (CTNB1_RAT); Li et al. 2002 Gene 283: 255-62.
• A RNAi agent specific to Beta-Catenin can be designed such that the sequence thereof completely matches that of the mRNA corresponding to the human Beta-Catenin gene and the homologous gene from a test animal. Thus, the exact same RNAi agent can be used in both test animals (e.g., rat, mouse, cynomolgus monkey, etc.) and humans. The sequences for the various Beta-Catenin genes have been determined in many species, including humans, mice and rats (as described above).
• The Beta-Catenin sequence in cynomolgus monkey (Macaca fascicularis, or “cyno”) has been determined.
• The alignment of the cyno and human (NM_001098210.1) Beta-Catenin mRNA sequences is shown below.

• Human	AGGATACAGCGGCTTCTGCGCGACTTATAAGAGCTCCTTGTGCGGCGCCATTTTAAGCCT	60
  Cyno	---------------------------------------------CGCCATTTTAAGCCT	15
  	***************
  Human	CTCGGTCTGTGGCAGCAGCGTTGGCCCGGCCCCGGGAGCGGAGAGCGAGGGGAGGCGGAG	120
  Cyno	CTTGGTCTGTGGCAGCCGTGTTGGCCCGGCCCCGAGAGCGGAGAGCGAGGGGAGGCGGAG	75
  	** ************* * *************** *************************
  Human	ACGGAGGAAGGTCTGAGGAGCAGCTTCAGTCCCCGCCGAGCCGCCACCGCAGGTCGAGGA	180
  Cyno	ACGGAGGAAGGTCCGAGGAGCAGCTTCAGTCCTCGCCGAGCCGCCACCGCAGGTCGAGGA	135
  	************* ****************** ***************************
  Human	CGGTCGGACTCCCGCGGCGGGAGGAGCCTGTTCCCCTGAGGGTATTTGAAGTATACCATA	240
  Cyno	CGGTCGGACTCCCGCGACGGGAGGAGCCTGTTCCCCTGAGGGTATTTGAAGTATACCATA	195
  	**************** *******************************************
  Human	CAACTGTTTTGAAAATCCAGCGTGGACAATGGCTACTCAAGCTGATTTGATGGAGTTGGA	300
  Cyno	CAACTGTTTTGAAAATCCAGCGTGGACAATGGCTACTCAAGCTGATTTGATGGAGTTGGA	255
  	************************************************************
  Human	CATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCT	360
  Cyno	CATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCT	315
  	************************************************************
  Human	GGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAA	420
  Cyno	GGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTCTCTGAGTGGTAAAGGCAA	375
  	************************************************************
  Human	TCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTC	480
  Cyno	TCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTC	435
  	************************************************************
  Human	TCAGTCCTTCACTCAAGAACAAGTAGCTGATATTGATGGACAGTATGCAATGACTCGAGC	540
  Cyno	TCAGTCCTTCACTCAAGAACAAGTAGCTGATATTGATGGACAGTATGCAATGACTCGAGC	495
  	************************************************************
  Human	TCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATC	600
  Cyno	TCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATC	555
  	************************************************************
  Human	TACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGAT	660
  Cyno	TACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGAT	615
  	************************************************************
  Human	GCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACG	720
  Cyno	GCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACG	675
  	************************************************************
  Human	TGCAATCCCTGAACTGACAAAACTGCTAAATGACGAGGACCAGGTGGTGGTTAATAAGGC	780
  Cyno	TGCAATCCCTGAACTGACAAAACTGCTAAATGATGAGGACCAGGTGGTGGTTAATAAGGC	735
  	********************************* **************************
  Human	TGCAGTTATGGTCCATCAGCTTTCTAAAAAGGAAGCTTCCAGACACGCTATCATGCGTTC	840
  Cyno	TGCAGTTATGGTCCATCAGCTTTCTAAAAAGGAAGCTTCCAGACACGCTATCATGCGTTC	795
  	************************************************************
  Human	TCCTCAGATGGTGTCTGCTATTGTACGTACCATGCAGAATACAAATGATGTAGAAACAGC	900
  Cyno	TCCTCAGATGGTGTCTGCTATTGTACGTACCATGCAGAATACAAATGATGTAGAAACAGC	855
  	************************************************************
  Human	TCGTTGTACCGCTGGGACCTTGCATAACCTTTCCCATCATCGTGAGGGCTTACTGGCCAT	960
  Cyno	TCGTTGTACCGCTGGGACCTTGCATAACCTTTCCCATCATCGGGAGGGCTTGTTGGCCAT	915
  	****************************************** ********  *******
  Human	CTTTAAGTCTGGAGGCATTCCTGCCCTGGTGAAAATGCTTGGTTCACCAGTGGATTCTGT	1020
  Cyno	CTTTAAGTCTGGAGGCATTCCTGCCCTGGTGAAAATGCTTGGTTCACCAGTGGATTCTGT	975
  	************************************************************
  Human	GTTGTTTTATGCCATTACAACTCTCCACAACCTTTTATTACATCAAGAAGGAGCTAAAAT	1080
  Cyno	GTTGTTTTATGCCATTACAACTCTCCACAACCTTTTATTACATCAAGAAGGAGCTAAAAT	1035
  	************************************************************
  Human	GGCAGTGCGTTTAGCTGGTGGGCTGCAGAAAATGGTTGCCTTGCTCAACAAAACAAATGT	1140
  Cyno	GGCAGTGCGTTTAGCTGGCGGGCTACAGAAAATGGTTGCCTTGCTCAACAAAACAAACGT	1095
  	****************** ***** ******************************** **
  Human	TAAATTCTTGGCTATTACGACAGACTGCCTTCAAATTTTAGCTTATGGCAACCAAGAAAG	1200
  Cyno	TAAATTCTTGGCTATTACGACAGACTGCCTTCAGATTTTAGCATATGGCAACCAAGAAAG	1155
  	********************************* ******** *****************
  Human	CAAGCTCATCATACTGGCTAGTGGTGGACCCCAAGCTTTAGTAAATATAATGAGGACCTA	1260
  Cyno	CAAGCTGATCATACTGGCTAGTGGTGGACCCCAAGCTTTAGTAAATATAATGAGGACCTA	1215
  	****** *****************************************************
  Human	TACTTACGAAAAACTACTGTGGACCACAAGCAGAGTGCTGAAGGTGCTATCTGTCTGCTC	1320
  Cyno	TACTTATGAGAAACTACTGTGGACCACAAGCAGAGTGCTGAAGGTGCTATCCGTCTGCTC	1275
  	****** ** ***************************************** ********
  Human	TAGTAATAAGCCGGCTATTGTAGAAGCTGGTGGAATGCAAGCTTTAGGACTTCACCTGAC	1380
  Cyno	TAGTAATAAGCCAGCTATTGTAGAAGCTGGTGGAATGCAAGCTTTAGGACTTCACCTGAC	1335
  	************ ***********************************************
  Human	AGATCCAAGTCAACGTCTTGTTCAGAACTGTCTTTGGACTCTCAGGAATCTTTCAGATGC	1440
  Cyno	AGATCCAAGTCAACGTCTTGTTCAGAACTGTCTTTGGACTCTCAGGAATCTTTCAGATGC	1395
  	************************************************************
  Human	TGCAACTAAACAGGAAGGGATGGAAGGTCTCCTTGGGACTCTTGTTCAGCTTCTGGGTTC	1500
  Cyno	TGCAACTAAACAGGAAGGGATGGAAGGTCTCCTTGGGACTCTTGTTCAGCTTCTGGGTTC	1455
  	************************************************************
  Human	AGATGATATAAATGTGGTCACCTGTGCAGCTGGAATTCTTTCTAACCTCACTTGCAATAA	1560
  Cyno	AGATGATATAAATGTGGTCACCTGTGCAGCTGGAATTCTTTCTAACCTCACTTGCAATAA	1515
  	************************************************************
  Human	TTATAAGAACAAGATGATGGTCTGCCAAGTGGGTGGTATAGAGGCTCTTGTGCGTACTGT	1620
  Cyno	TTATAAGAATAAGATGATGGTCTGCCAAGTGGGTGGTATAGAGGCTCTTGTGCGTACTGT	1575
  	********* **************************************************
  Human	CCTTCGGGCTGGTGACAGGGAAGACATCACTGAGCCTGCCATCTGTGCTCTTCGTCATCT	1680
  Cyno	CCTTCGGGCTGGTGACAGGGAAGACATCACTGAGCCTGCCATCTGTGCTCTTCGTCATCT	1635
  	************************************************************
  Human	GACCAGCCGACACCAAGAAGCAGAGATGGCCCAGAATGCAGTTCGCCTTCACTATGGACT	1740
  Cyno	GACCAGCCGACACCAAGAAGCAGAGATGGCCCAGAATGCAGTTCGCCTTCACTATGGACT	1695
  	************************************************************
  Human	ACCAGTTGTGGTTAAGCTCTTACACCCACCATCCCACTGGCCTCTGATAAAGGCTACTGT	1800
  Cyno	ACCAGTTGTGGTTAAGCTCTTACACCCACCATCCCACTGGCCTCTGATAAAGGCTACTGT	1755
  	************************************************************
  Human	TGGATTGATTCGAAATCTTGCCCTTTGTCCCGCAAATCATGCACCTTTGCGTGAGCAGGG	1860
  Cyno	TGGATTGATTCGAAATCTTGCCCTTTGTCCAGCAAATCATGCACCTTTGCGTGAGCAGGG	1815
  	****************************** *****************************
  Human	TGCCATTCCACGACTAGTTCAGTTGCTTGTTCGTGCACATCAGGATACCCAGCGCCGTAC	1920
  Cyno	TGCCATTCCACGACTAGTTCAGTTGCTTGTTCGTGCACATCAGGATACCCAGCGCCGTAC	1875
  	************************************************************
  Human	GTCCATGGGTGGGACACAGCAGCAATTTGTGGAGGGGGTCCGCATGGAAGAAATAGTTGA	1980
  Cyno	GTCCATGGGTGGGACACAGCAGCAATTTGTGGAGGGGGTCCGCATGGAAGAAATAGTTGA	1935
  	************************************************************
  Human	AGGTTGTACCGGAGCCCTTCACATCCTAGCTCGGGATGTTCACAACCGAATTGTTATCAG	2040
  Cyno	AGGTTGTACTGGAGCCCTTCACATCCTAGCTCGGGATGTTCACAACCGAATTGTAATCAG	1995
  	********* ******************************************** *****
  Human	AGGACTAAATACCATTCCATTGTTTGTGCAGCTGCTTTATTCTCCCATTGAAAACATCCA	2100
  Cyno	AGGACTAAATACCATTCCATTGTTTGTGCAGCTGCTTTATTCTCCCATTGAAAACATCCA	2055
  	************************************************************
  Human	AAGAGTAGCTGCAGGGGTCCTCTGTGAACTTGCTCAGGACAAGGAAGCTGCAGAAGCTAT	2160
  Cyno	AAGAGTAGCTGCAGGGGTCCTCTGTGAACTTGCTCAGGACAAGGAAGCTGCAGAAGCGAT	2115
  	********************************************************* **
  Human	TGAAGCTGAGGGAGCCACAGCTCCTCTGACAGAGTTACTTCACTCTAGGAATGAAGGTGT	2220
  Cyno	TGAAGCTGAGGGAGCCACAGCTCCTCTGACAGAGTTACTTCACTCTAGGAATGAAGGTGT	2175
  	************************************************************
  Human	GGCGACATATGCAGCTGCTGTTTTGTTCCGAATGTCTGAGGACAAGCCACAAGATTACAA	2280
  Cyno	GGCGACGTATGCAGCTGCTGTTTTGTTCCGAATGTCTGAGGACAAGCCACAAGATTACAA	2235
  	****** *****************************************************
  Human	GAAACGGCTTTCAGTTGAGCTGACCAGCTCTCTCTTCAGAACAGAGCCAATGGCTTGGAA	2340
  Cyno	GAAACGGCTTTCAGTTGAGCTGACCAGCTCTCTCTTCAGAACGGAGCCAATGGCTTGGAA	2295
  	****************************************** *****************
  Human	TGAGACTGCTGATCTTGGACTTGATATTGGTGCCCAGGGAGAACCCCTTGGATATCGCCA	2400
  Cyno	TGAGACTGCGGATCTTGGACTTGATATTGGTGCCCAGGGAGAACCCCTTGGATATCGCCA	2355
  	********* **************************************************
  Human	GGATGATCCTAGCTATCGTTCTTTTCACTCTGGTGGATATGGCCAGGATGCCTTGGGTAT	2460
  Cyno	GGATGATCCTAGCTATCGTTCTTTTCACTCTGGTGGATATGGCCAGGATGCCTTGGGTAT	2415
  	************************************************************
  Human	GGACCCCATGATGGAACATGAGATGGGTGGCCACCACCCTGGTGCTGACTATCCAGTTGA	2520
  Cyno	GGACCCCATGATGGAACATGAGATGGGTGGCCACCACCCTGGTGCTGACTATCCAGTTGA	2475
  	************************************************************
  Human	TGGGCTGCCAGATCTGGGGCATGCCCAGGACCTCATGGATGGGCTGCCTCCAGGTGACAG	2580
  Cyno	TGGGCTGCCAGATCTGGGACATGCCCAGGACCTCATGGATGGGCTGCCTCCAGGTGATAG	2535
  	****************** ************************************** **
  Human	CAATCAGCTGGCCTGGTTTGATACTGACCTGTAAATCATCCTTTAG--------------	2626
  Cyno	CAATCAGCTGGCCTGGTTTGATACTGACCTGTAAATCATCCTTTAGCTGTATTGTCTGAA	2595
  	**********************************************
  Human	------------------------------------------------------------
  Cyno	CTTGCATTGTGATTGGCCTGTAGAGTTGCTGAGAGGGCTCGAGGGGTGGGCTGGTATCTC	2655
  Human	------------------------------------------------------------
  Cyno	AGAAAGTGCCTGACACACTAACCAAGCTGAGTTTCCTATGGGAACAATTGAAGTAAACTT	2715
  Human	-------------------------GAGTAACAATACAAATGGATTTTGGGAGTGACTCA	2661
  Cyno	TTTGTTCTGGTCCTTTTTGGTCGAGGAGTAACAATACAAATGGATTTTGGGAGTGACTCA	2775
  	***********************************
  Human	AGAAGTGAAGAATGCACAAGAATGGATCACAAGATGGAATTTATCAAACCCTAGCCTTGC	2721
  Cyno	AGAAGTGAAGAATGCACAAGAATGGATCACAAGATGGAATTTATCAAACCCTAGCCTTGC	2835
  	************************************************************
  Human	TTGTTAAATTTTTTTTTTTTTTTTTTTAAGAATATCTGTAATGGTACTGACTTTGCTTGC	2781
  Cyno	TTGTTAAATTTTTTTTTTTTTTTTTTTAAGAATATCTGTAATGGTACTGACTTTGCTTGC	2895
  	************************************************************
  Human	TTTGAAGTAGCTCTTTTTTTTTTTTTTTTTTTTTTTTTGCAGTAACTGTTTTTTAAGTCT	2841
  Cyno	TTTGAAGTAGCTCTTTTTTTTTTTTTTTTTTTTTTTTTGCAGTAACTGTTTTTTAAGTCT	2955
  	************************************************************
  Human	CTCGTAGTGTTAAGTTATAGTGAATACTGCTACAGCAATTTCTAATTTTTAAGAATTGAG	2901
  Cyno	CTCGTAGTGTTAAGTTATAGTGAATACTGCTACAGCAATTTCTAATTTTTAAGAATTGAG	3015
  	************************************************************
  Human	TAATGGTGTAGAACACTAATTCATAATCACTCTAATTAATTGTAATCTGAATAAAGTGTA	2961
  Cyno	TAATGGTGTAGAACACTAATTCATAATCACTCTAAT-AATTGTAATCTGAATAAAGTGTA	3074
  	************************************ ***********************
  Human	ACAATTGTGTAGCCTTTTTGTATAAAATAGACAAATAGAAAATGGTCCAATTAGTTTCCT	3021
  Cyno	ACA-TTGTGTAGCCTTTTTGTATAAAATAGACAAATAGAAAATGGTCCAATTAGTTTCCT	3133
  	*** ********************************************************
  Human	TTTTAATATGCTTAAAATAAGCAGGTGGATCTATTTCATGTTTTTGATCAAAAACT--AT	3079
  Cyno	TTTTAATATGCTTAAAATAAGCAGGTGGATCTATTTCATGTTTTTGATCAAAAACTTTAT	3193
  	********************************************************  **
  Human	TTGGGATATGTATGGGTAGGGTAAATCAGTAAGAGGTGTTATTTGGAACCTTGTTTTGGA	3139
  Cyno	TTGGGATATGTATGGGTAGGGTAAATCAGTAAGAGGTGTTATTTGGAACCTTGTTTTGGA	3253
  	************************************************************
  Human	CAGTTTACCAGTTGCCTTTTATCCCAAAGTTGTTGTAACCTGCTGTGATACGATGCTTCA	3199
  Cyno	CAGTTTACCAGTTGCCTTTTATCCCAAAGTTGTTGTAACCTGCTGTGATACAATGCTTCA	3313
  	*************************************************** ********
  Human	AGAGAAAATGCGGTTATAAAAAATGGTTCAGAATTAAACTTTTAATTCATTCGATTG	3256
  Cyno	AGAGAAAATGCGGTTATAAAAAATGGTTCAGAA------------------------	3346
  	*********************************
  Human	(SEQ ID NO: 4112)
  Cyno	(SEQ ID NO: 4113)

• The start (ATG) and stop (TGA) of the cyno and human sequences are in bold, underlined. Nucleotides matching between the human and cyno sequences are marked with an asterick (*). Whether or not a given sequence (e.g., a first or second strand of a siRNA or duplex) matches the sense or anti-sense strand of the Beta-Catenin sequence can be readily determined by comparison of the sequences above (SEQ ID NOs: 4112 and 4113).
• Additional Embodiments of a RNAi Agent to Beta-Catenin
• The present disclosure encompasses various embodiments of RNAi agents to Beta-Catenin.
• In one embodiment, the Beta-Catenin RNAi agent of the present disclosure comprises a sequence which is identical in the human, rat and cyno Beta-Catenin mRNAs. This sequence identity facilitates animal testing prior to human testing. In another embodiment, the Beta-Catenin RNAi agent comprises a sequence which is identical in the human, mouse and cyno Beta-Catenin mRNAs. In another embodiment, the Beta-Catenin RNAi agent comprises a sequence which is identical in the human and mouse Beta-Catenin mRNAs. In another embodiment, the Beta-Catenin RNAi agent comprises a sequence which is identical in the human and rat cyno Beta-Catenin mRNAs. In another embodiment, the Beta-Catenin RNAi agent comprises a sequence which is identical in the human, mouse and rat Beta-Catenin mRNAs. In another embodiment, the Beta-Catenin RNAi agent comprises a sequence which is identical in the human, rat and cyno Beta-Catenin mRNAs.
• In one embodiment, the Beta-Catenin RNAi agent comprises a sequence which does not match that of any other mRNA. In one embodiment, the Beta-Catenin RNAi agent comprises a sequence which differs from all other known non-Beta-Catenin mRNAs by at least 0, 1, 2 or 3 nucleotides. In various embodiments, the Beta-Catenin RNAi agent does knock-down any other gene by more than 5, 10, 15, 20, 25, 30, or 40%. The ability of the Beta-Catenin RNAi agent to knock down other genes can be tested in vitro, or by using arrays of various genes.
• Various mutations in Beta-Catenin are known; many of these are involved in Beta-Catenin-related diseases. These include mutations of the residues at 33, 37, 41 and 45, but disease-associated mutations have also been found at positions 8, 11, 13, 21, 24, 25, 28, 29, 32, 34, 39, 47, 48 and 55. In various embodiments of the present disclosure, RNAi agents can be devised to preferentially target the mutated (rather than wildtype) form of Beta-Catenin.
• In other embodiments, the RNAi agents of the present disclosure bind to the 5′ or 3′ UTR [untranslated region(s)].
• The efficacy of a RNAi agent in reducing the level of Beta-Catenin can be measured directly, e.g., measuring the levels of Beta-Catenin mRNA abundance or levels or cellular distribution of the protein itself. For example, the accumulation of Beta-Catenin in the cytoplasm and/or nucleus is associated with various disease states. After administration of a RNAi agent, cells and tissues can be tested for the accumulation of Beta-Catenin in the cytoplasm and nucleus. Alternatively, the efficacy of the RNAi can be measured indirectly by measuring the level of any one or more of the known activities of Beta-Catenin. For example, localization of Beta-Catenin to the nucleus can lead to transcription of various genes, including c-myc. After administration of a RNAi agent to Beta-Catenin, the expression of c-myc or other genes activated by Beta-Catenin can be measured.
• In one embodiment, the Beta-Catenin RNAi agent of the present disclosure is administered to a patient in need thereof (e.g., a patient suffering from, suspected of having, or predisposed for, adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases).
• The patient can also be administered more than one RNAi agent specific to Beta-Catenin. In one embodiment, the Beta-Catenin RNAi agent(s) of the present disclosure can optionally be administered along with one or more additional pharmaceutical agent appropriate for that disease. In one embodiment, the Beta-Catenin RNAi agent(s) of the present disclosure can be optionally administered along with any other appropriate additional treatment, wherein the additional treatment can be a composition or a method.
• Various disease states are associated with mutations in Beta-Catenin (such as those listed above), which result in over-expression, hyper-activity and/or improper cellular compartmentalization of Beta-Catenin. Mutations in components other than Beta-Catenin can also activate the Wnt signaling pathway. For example, APC (adenomatous polyposis coli) normally controls Beta-Catenin activity. APC normally builds a complex with glycogen synthase kinase 3-beta (GSK-3beta) and axin. This complex binds Beta-Catenin in the cytoplasm. With the help of casein kinase (CK1), which carries out an initial phosphyrlation of Beta-Catenin, GSK-3beta is able to phosphorylate Beta-Catenin a second time. This targets Beta-Catenin for ubiquitination and degradation by cellular proteosomes and prevents translocation of Beta-Catenin to the nucleus. APC mutations thus can result in constitutive activation of the Wnt signaling pathway. RNAi agents to Beta-Catenin can thus be administered to patients with disease strates associated not only with mutations in Beta-Catenin but also in related mutations in other components (such as APC) of the Wnt signaling pathway.
• In the case of adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases, the RNAi agent(s) and additional disease treatment(s) can be administered in any order, simultaneously or sequentially, or in one or multiple doses over time.
• In the treatment of these Beta-Catenin-related diseases, the RNAi agent(s) and additional disease treatment(s) can be administered in any order, simultaneously or sequentially, or in multiple doses over time. Administration of the RNAi agent and the additional treatment can be, for example, simultaneous, concurrent, separate or sequential.
• Simultaneous administration may, e.g., take place in the form of one fixed combination with two or more active ingredients, or by simultaneously administering two or more active ingredients that are formulated independently. Sequential use (administration) preferably means administration of one (or more) components of a combination at one time point, other components at a different time point, that is, in a chronically staggered manner, preferably such that the combination shows more efficiency than the single compounds administered independently (especially showing synergism). Separate use (administration) preferably means administration of the components of the combination independently of each other at different time points, preferably meaning that the components (a) and (b) are administered such that no overlap of significant measurable blood levels of both compounds are present in an overlapping manner (at the same time).
• Also combinations of two or more of sequential, separate and simultaneous administration are possible, preferably such that the combination component-drugs show a joint therapeutic effect that exceeds the effect found when the combination component-drugs are used independently at time intervals so large that no mutual effect on their therapeutic efficiency can be found, a synergistic effect being especially preferred.
• The term “delay of progression” as used herein means administration of the combination to patients being in a pre-stage or in an early phase, of the first manifestation or a relapse of the disease to be treated, in which patients, e.g., a pre-form of the corresponding disease is diagnosed or which patients are in a condition, e.g., during a medical treatment or a condition resulting from an accident, under which it is likely that a corresponding disease will develop.
• “Jointly therapeutically active” or “joint therapeutic effect” means that the compounds may be given separately (in a chronically staggered manner, especially a sequence-specific manner) in such time intervals that they preferably, in the warm-blooded animal, especially human, to be treated, still show a (preferably synergistic) interaction (joint therapeutic effect). Whether this is the case, can inter alia be determined by following the blood levels, showing that both compounds are present in the blood of the human to be treated at least during certain time intervals.
Additional Definitions
• For convenience, the meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in other parts of this specification and its definition provided in this document, the definition in this document shall prevail.
• As used throughout this disclosure, articles such as “a” and “an” refer to one or more than one (at least one) of the grammatical object of the article.
• RNAi Agents to Beta-Catenin
• In one embodiment, the present disclosure pertains to a Beta-Catenin RNAi agent or other anti-sense nucleic acid complementary to a mRNA encoding the Beta-Catenin gene (or portion thereof), or a recombinant expression vector encoding encoding at least one strand of the siRNA (RNAi agent) or a composition comprising the antisense nucleic acid that can function as an RNAi agent as defined below.
• As used herein, an “anti-sense” nucleic acid comprises a nucleotide sequence complementary to a “sense” nucleic acid encoding the Beta-Catenin protein (e.g., complementary to the coding strand of a double-stranded DNA, complementary to an mRNA or complementary to the coding strand of a Beta-Catenin gene).
• As used herein, the term “RNAi agent to Beta-Catenin,” “RNAi agent specific to Beta-Catenin,” “iRNA agent to Beta-Catenin,” “siRNA to Beta-Catenin”, “Beta-Catenin siRNA” and the like refer to a siRNA (short inhibitory RNA), shRNA (short or small hairpin RNA), iRNA (interference RNA) agent, RNAi (RNA interference) agent, dsRNA (double-stranded RNA), microRNA, and the like, and refer to a composition which specifically targets, is specific to, and/or binds to a mRNA corresponding to the Beta-Catenin gene. As used herein, the term “antisense nucleic acid” or “composition comprising an anti-sense nucleic acid” and the like is broadly meant to encompass any composition comprising at least one nucleic acid strand which is anti-sense to its target; this includes, but is not limited to, any siRNA, shRNA, iRHA, dsRNA, microRNA, antisense oligonucleotide, and any other composition comprising an anti-sense nucleic acid.
• As used herein, the terms “iRNA” and “RNAi” refers to an agent that contains RNA (or a derivative thereof), and which mediates the targeted cleavage of another RNA transcript via an RNA-induced silencing complex (RISC) pathway. In one embodiment, the RNAi agent is an oligonucleotide composition that activates the RISC complex/pathway. In another embodiment, the RNAi agent comprises an anti-sense strand sequence (anti-sense oligonucleotide). RNAi agents include, for example, siRNAs, dsRNAs and shRNAs. The RNAi agents can be wholly RNA, or can comprise a backbone or individual nucleotides which are not RNA, such as LNA, GNA, TNA, boranophosphate RNA, FANA, etc. Individual nucleotides can be replaced by DNA (e.g., the terminal UU, TT, or the like) or individual nucleotides at the 5′ end or internally. However, in no case does the disclosure contemplate the RNAi agent comprising two strands which are completely DNA (e.g., a double-stranded DNA).
• In one embodiment, the RNAi comprises a single strand. This single-stranded RNAi agent oligonucleotide or polynucleotide can comprise the sense or antisense strand, as described by Sioud 2005 J. Mol. Biol. 348:1079-1090, and references therein. Thus the disclosure encompasses RNAi agents with a single strand comprising either the sense or antisense strand of an RNAi agent described herein.
• The RNAi agent(s) of the present disclosure target (e.g., bind to, anneal to, etc.) the Beta-Catenin mRNA. The use of the RNAi agent specific to Beta-Catenin results in a decrease of Beta-Catenin activity, level and/or expression, e.g., a “knock-down” or “knock-out” of the target gene or target sequence. Particularly, in one embodiment, in the case of a disease state characterized by over-expression or hyper-activity of Beta-Catenin, administration of a RNAi agent to Beta-Catenin knocks down the Beta-Catenin target enough to restore a normal level of Beta-Catenin activity.
• In one embodiment, the RNAi comprises a single strand (such as an shRNA, as described herein). In other embodiments, the RNAi agent comprises a single strand because the sense and anti-sense strands are contiguous, connected by a loop, or otherwise linked.
• In various embodiments, one or both strands are nicked.
• In one embodiment, a single-stranded RNAi agent oligonucleotide or polynucleotide can comprise the sense and/or antisense strand. See, e.g., Sioud 2005 J. Mol. Biol. 348:1079-1090, and references cited therein. Thus the present disclosure encompasses RNAi agents with a single strand comprising either the sense or antisense strand of a RNAi agent described herein.
• RNAi agents that are particularly useful for this disclosure include those which can bind specifically to a region of the Beta-Catenin mRNA, and have one or more of the following qualities: binding in the coding segment of Beta-Catenin; binding at or near the junction of the 5′ untranslated region and the start of the coding segment; binding at or near the translational start site of the mRNA; binding in the third exon of the Beta-Catenin gene; binding at or near junctions of exons and introns; little or no binding to the mRNAs of other genes (little or no “off-target effects”); binding to the Beta-Catenin mRNA in or near a region or regions that is not double-stranded or a stem region, e.g., in a loop or single-stranded portion; eliciting little or no immunogenicity; binding in a segment of the Beta-Catenin mRNA sequence which is conserved among various animal species (including human, mouse, rat, cynomolgus monkey, etc.), as the presence of a conserved sequence facilitates testing using various laboratory animals; binding to double-stranded region(s) of the mRNA; binding to an AT-rich region (e.g., at least about 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60% AT-rich); and/or lacking particular sequences known or suspected to decrease siRNA activity, e.g., the presence of a GG sequence at the 5′ end, which may decrease separation of the double-stranded portion of the RNAi agent. In various embodiments, the RNAi agent specific to Beta-Catenin can be a double-stranded RNA having any one or more of these qualities.
• The term “double-stranded RNA” or “dsRNA,” as used herein, refers to a RNAi agent comprising a first and a second strand; e.g., a composition that includes an RNA molecule or complex of molecules having a hybridized duplex region (i.e., a region where the nucleotide bases from the first strand and the second strand are paired) that comprises two anti-parallel and substantially complementary nucleic acid strands, which will be referred to as having “sense” and “anti-sense” orientations with respect to a target RNA. The anti-sense strand, with respect to the mRNA target, is also called the “guide” strand, and the sense strand is also called the “passenger” strand. The passenger strand can include at least one or more of the following: one or more extra nucleotides (e.g., a bulge or 1 nt loop) compared to the other strand, a nick, a gap, etc., compared to the other strand. In various embodiments, the RNAi agent comprises a first strand and a second strand. In various embodiments, the first strand is the sense strand and the second strand is the anti-sense strand. In other embodiments, the first strand is the anti-sense strand and the second strand is the sense strand.
• The duplex region can be of any length that permits specific degradation of a desired target RNA through a RISC pathway, but will typically range from 9 to 36 base pairs (“bp”) in length, e.g., 15-30 base pairs in length. Considering a duplex between 9 and 36 base pairs, the duplex can be any length in this range, for example, 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, or 36 base pairs (bp) and any sub-range therebetween, including, but not limited to 15-30 base pairs, 15-26 base pairs, 15-23 base pairs, 15-22 base pairs, 15-21 base pairs, 15-20 base pairs, 15-19 base pairs, 15-18 base pairs, 15-17 base pairs, 18-30 base pairs, 18-26 base pairs, 18-23 base pairs, 18-22 base pairs, 18-21 base pairs, 18-20 base pairs, 19-30 base pairs, 19-26 base pairs, 19-23 base pairs, 19-22 base pairs, 19-21 base pairs, 19-20 base pairs, 19 base pairs, 20-30 base pairs, 20-26 base pairs, 20-25 base pairs, 20-24 base pairs, 20-23 base pairs, 20-22 base pairs, 20-21 base pairs, 20 base pairs, 21-30 base pairs, 21-26 base pairs, 21-25 base pairs, 21-24 base pairs, 21-23 base pairs, 21-22 base pairs, 21 base pairs, 22 base pairs, or 23 base pairs. dsRNAs generated in the cell by processing with Dicer and similar enzymes are generally in the range of 19-22 base pairs in length. One strand of the duplex region of a dsRNA comprises a sequence that is substantially complementary to a region of a target RNA. The two strands forming the duplex structure can be from a single RNA molecule having at least one self-complementary duplex region, or can be formed from two or more separate RNA molecules that hybridize to form the duplex. Where the duplex region is formed from two strands of a single molecule, the molecule can have a duplex region separated by a single-stranded chain of nucleotides (herein referred to as a “hairpin loop”, e.g., such as found in a shRNA construct) between the 3′-end of one strand and the 5′-end of the respective other strand forming the duplex structure. The hairpin loop can comprise at least one unpaired nucleotide; in some embodiments the hairpin loop can comprise at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 20, at least 23 or more unpaired nucleotides. Where the two substantially complementary strands of a dsRNA are comprised by separate RNA molecules, those molecules need not, but can be covalently connected. Where the two strands are connected covalently by a hairpin loop, the construct is generally referred to herein and in the art as a “shRNA.” Where the two strands are connected covalently by means other than a hairpin loop, the connecting structure is referred to as a “linker.”
• The terms “RNAi agent” and “siRNA” are also used herein to refer to a dsRNA as described above, useful for RNA interference.
• In various embodiments of the present disclosure, the composition pertains to RNAi agents to Beta-Catenin comprising a sense strand comprising at least 15 contiguous nt with 0, 1, 2 or 3 mismatches from the sense strand, and/or an anti-sense strand comprising at least 15 contiguous nt with 0, 1, 2, or 3 mismatches from the anti-sense strand of any RNAi agent disclosed herein, particularly in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• RNAi Agents to Beta-Catenin Comprising Mismatches from the Disclosed Sequences
• Various specific embodiments of a RNAi agent to Beta-Catenin are disclosed herein; example sequences are provided in Tables 1, 2 and 3. Specific embodiments of the present disclosure include RNAi agents which comprise sequences differing by 0, 1, 2, or 3 nt (nucleotides) or bp [basepair(s)] (e.g., with 0, 1, 2 or 3 mismatches) from any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• A mismatch is defined herein as a difference between the base sequence or length when two sequences are maximally aligned and compared. A mismatch is defined as a position wherein the base of one sequence does not match the base of the other sequence. Thus, a mismatch is counted, for example, if a position in one sequence has a particular base (e.g., A), and the corresponding position on the other sequence has a different base (e.g., G). Substitution of A, for example, with T, C, G or U would constitute a mismatch. Substitution of G with T, A, C or U would also constitute a mismatch. Substitution of C with T, G, A or U would also constitute a mismatch. Substitution of U with A, C or G would constitute a mismatch. Note, however, that on a given strand, a U can be replaced by T (either as RNA or, preferably, DNA, e.g., 2′-deoxy-thymidine); the replacement of a U with a T is not a mismatch, as either U or A can pair with A on the opposite strand. The RNAi agent can thus comprise some DNA bases, e.g., T, or a terminal TT or UU.
• A mismatch is also counted, e.g., if a position in one sequence has a base (e.g., A), and the corresponding position on the other sequence has no base (e.g., that position is an abasic nucleotide, which comprises a phosphate-sugar backbone but no base). A single-stranded nick in either sequence (or in the sense or anti-sense strand) is not counted as mismatch. Thus, as a non-limiting example, no mismatch would be counted if one sequence comprises the sequence AG, but the other sequence comprises the sequence AG with a single-stranded nick between the A and the G. If one sequence comprises a C, and the other sequence comprises a modified C (e.g., 2′-modification) at the same position, no mismatch would be counted.
• In addition, no mismatches are counted if modifications are made to the sugar, phosphate, or backbone of the RNAi agent without modifying the base. Thus, a sequence of UGGUGCUGACUAUCCAGUU (SEQ ID NO: 429) as an RNA and the same sequence as a PNA (peptide nucleic acid) have 0 mismatches from each other.
• It is also noted that the sequences of the RNAi agents in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9 include sequences which comprise modifications, as detailed in Table 3. For example, one modified variant of the RNAi agent AD-18892 comprises strands of the sequences uGGuGcuGAcuAuccAGuudTdT (SEQ ID NO: 6132) and AACUGGAuAGUcAGcACcAdTdT (SEQ ID NO: 660). It is noted that dTdT (2′-deoxy-thymidine-5′-phosphate and 2′-deoxy-thymidine-5′-phosphate), or in some cases, TT or UU, is added as a cap or extension to both 3′-ends, but this cap or extension is not included in the calculation of the total number of mismatches. In addition, the sequence uGGuGcuGAcuAuccAGuu (SEQ ID NO: 1) comprises modifications from the corresponding portion of the Beta-Catenin gene, or UGGUGCUGACUAUCCAGUU (SEQ ID NO: 4771). In this case, lowercase “c” represents 2′-O-methylcytidine-5′-phosphate, and lowercase “u” represents 2′-O-methyluridine-5′-phosphate. Uppercase “A”, “C”, “G” and “U” represent the un-modified adenosine-5′-phosphate, cytidine-5′-phosphate, guanosine-5′-phosphate, and uridine-5′-phosphate, respectively. The substitution of modified c for unmodified C does not count as a mismatch in numbering the 0, 1, 2, or 3 mismatches between sequences. This is true of all sequences in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. Thus, an equal number of mismatches would be calculated (a) between a test sequence and a modified sequence (e.g., that of AD-18892 or any other sequence in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9), and (b) between the same test sequence and the corresponding unmodified sequence from the Beta-Catenin gene (e.g., the portion of the Beta-Catenin gene corresponding to AD-18892 or any other sequence in Table 1), and (c) between a modified sequence and a differently modified sequence which have the same base sequence.
• In one particular embodiment, the present disclosure comprises a RNAi agent comprising a anti-sense strand comprising at least 15 or 19 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand of: any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• It is noted that the present disclosure pertains to “modified and unmodified variants” of the disclosed sequences.
• An “unmodified variant” (also known as a “generic”) of a particular sequence is the corresponding portion of Beta-Catenin without any modifications. For example, a modified variant (or “generic”) of AD-18892 comprises a strand of the sequence uGGuGcuGAcuAuccAGuudTdT (SEQ ID NO: 6132); the corresponding “unmodified variant” is the corresponding portion of the wild-type Beta-Catenin sequence without modifications or terminal dTdT, namely, UGGUGCUGACUAUCCAGUU (SEQ ID NO: 6140), as described above. The “unmodified variants” of the sequences of Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9 have the identical sequence, without base modifications or terminal dTdT. A given sequence and an “unmodified variant” of it differ by 0 nt (and have no mismatches).
• A “modified variant” of a particular sequence comprises one or more (or one or more fewer) modifications to the backbone, sugar, phosphate or base, but do not have any base substitutions (e.g., G for C, or A for G); thus a given sequence and a modified variant thereof differ by 0 nt (and have no mismatches). A modified variant of the sequence of uGGuGcuGAcuAuccAGuu (SEQ ID NO: 1) is, as a non-limiting example, UGGuGcuGAcUAuccAGuu (SEQ ID NO: 6089). As another example, a given sequence [e.g., uGGuGcuGAcuAuccAGuu (SEQ ID NO: 1)] as a RNA and the same sequence as a PNA are modified variants of each other and differ by 0 nt (and have no mismatches). Similarly, the same sequence (with no base substitutions) as a locked nucleic acid (LNA), Morpholino, threose nucleic acid (TNA), or glycol nucleic acid (GNA) or FANA would be a modified variant which has 0 mismatches.
• As detailed below, substituting a single nucleotide at a given position with a modified version of the same nucleotide would produce a modified variant (with 0 mismatches).
• In another particular embodiment, the RNAi agent comprises a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sense strand of any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• RNAi agents to Beta-Catenin of the present disclosure can be used in RNA interference.
• Modifications of RNAi Agent Sequences
• The present disclosure encompasses both unmodified sequences and example modified sequences, such as those disclosed in Tables 1, 2 and 3.
• The present disclosure further encompasses any other modification of a disclosed sequence (e.g., a modified variant).
• For example, the disclosure encompasses a RNAi agent with a substitution of a single nucleotide at a given position with a modified version of the same nucleotide. Thus a nucleotide (A, G, C or U) can be replaced by the corresponding 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3) w, or 2,6-diaminopurine.
• Additional modified variants include the addition of any other moiety (e.g., a radiolabel or other tag or conjugate) to the RNAi agent; provided that the base sequence is identical, the addition of other moieties produces a “modified variant” (with no mismatches).
• Various sets of modifications can be used. These include the following formats, which are used in various screens disclosed herein.
A22S26A22 a All UA as 2′-OMe-U A and all CA as 2′-OMe-C AS26 a All U as 2′-OMe-U and all C as 2′-OMe-C
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
A25S27A25 a wt RNAS27 a wt RNA
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
A48S26
• A48 a All UA as 2′-OMe-U A and all CA as 2′-OMe-C A, first 5′-N is DNA
S26 a All U as 2′-OMe-U and all C as 2′-OMe-C
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
A51 S26
• A51 a All U as 2′-OMe-U and all C as 2′-OMe-C, except pos. 1, 2 and 14
S26 a All U as 2′-OMe-U and all C as 2′-OMe-C
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
A52S36A52 a 2′-OMe-N at pos. 3, 7, 10 and 13, 2′-MOE-N at pos. 18 and 19S36 a 2′-OMe-N at pos. 4, 8, 12 and 15, 2′-MOE-N at pos. 1, 2, 18 and 19
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
A53S37A53 a 2′-MOE-N at pos. 3, 7, 10, 13, 18 and 19S37 a 2′-MOE-N at pos. 1, 2, 4, 8, 12, 15, 18 and 19
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
A54S36A54 a 2′-OMe-N at pos. 3, 7, 10 and 13, 2′-MOE-N at pos. 18 and 19, DNA at pos. 1S36 a 2′-OMe-N at pos. 4, 8, 12 and 15, 2′-MOE-N at pos. 1, 2, 18 and 19
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
A55S36A55 a 2′-OMe-N at pos. 3, 7, 10 and 13, 2′-MOE-N at pos. 18 and 19,2′-F—N at pos. 1S36 a 2′-OMe-N at pos. 4, 8, 12 and 15, 2′-MOE-N at pos. 1, 2, 18 and 19
• All 3′ overhangs as 2′-OMe-U 2′-OMe-U
• In addition to these modifications and patterns (e.g, formats) for modifications, other modifications or sets of modifications of the sequences provided can be generated using common knowledge of nucleic acid modification.
• RNA Interference
• RNA interference (RNAi) is a post-transcriptional, targeted gene-silencing technique that uses double-stranded RNA (dsRNA) to degrade messenger RNA (mRNA) containing the same sequence as the dsRNA. The process of RNAi occurs when ribonuclease III (Dicer) cleaves the longer dsRNA into shorter fragments called siRNAs. siRNAs (small interfering RNAs) produced by Dicer are typically about 21 to 23 nucleotides long and comprise about 19 base pair duplexes (though artificial siRNAs or RNAi agents can be shorter, and/or blunt-ended, and/or comprises one or more endcaps). The smaller RNA segments then mediate the degradation of the target mRNA. Dicer has also been implicated in the excision of 21- and 22-nucleotide small temporal RNAs (stRNAs) from precursor RNA of conserved structure that are implicated in translational control. Hutvagner et al. 2001 Science 293: 834. The RNAi response also features an endonuclease complex, commonly referred to as an RNA-induced silencing complex (RISC), which mediates cleavage of single-stranded mRNA complementary to the anti-sense strand of the RNAi agent. Cleavage of the target RNA takes place in the middle of the region complementary to the anti-sense strand of the siRNA duplex.
• In one aspect, an RNA interference agent includes a single-stranded RNA that interacts with a target RNA sequence to direct the cleavage of the target RNA. Without wishing to be bound by theory, long double-stranded RNA introduced into plants and invertebrate cells is broken down into siRNA by a Type III endonuclease known as Dicer. Sharp et al. 2001 Genes Dev. 15:485. Dicer, a ribonuclease-III-like enzyme, processes the dsRNA into 19-23 base pair short interfering RNAs with characteristic two base 3′ overhangs. Bernstein et al. 2001 Nature 409:363. The siRNAs are then incorporated into an RNA-induced silencing complex (RISC) where one or more helicases unwind the siRNA duplex, enabling one of the now-unpaired siRNA strands to act as a “guide” strand to guide target recognition. Nykanen et al. 2001 Cell 107:309. Upon binding of the anti-sense guide strand to the appropriate target mRNA, one or more endonucleases within the RISC cleaves the target to induce silencing. Elbashir et al. 2001 Genes Dev. 15:188. Thus, in one aspect the present disclosure relates to a single-stranded RNA that promotes the formation of a RISC complex to effect silencing of the target gene.
• RNA interference has also been studied in a variety of systems. Work inDrosophilaembryonic lysates (Elbashir et al. 2001 EMBO J. 20: 6877 and Tuschl et al. International PCT Publication No. WO 01/75164) has revealed certain requirements for siRNA length, structure, chemical composition, and sequence that are essential to mediate efficient RNAi activity in a variety of systems, including especially mammals. These studies have shown that 21-nucleotide siRNA duplexes are most active when containing 3′-terminal dinucleotide overhangs. Substitution of the 3′-terminal siRNA overhang nucleotides with 2′-deoxy nucleotides (2′-H) was tolerated. In addition, a 5′-phosphate on the target-complementary strand of a siRNA duplex is usually required for siRNA activity. Most importantly for therapeutic uses, siRNA duplexes shorter than 50 bp or so do not activate the interferon response in mammalian cells. See., e.g., Tuschl et al., WO 01/752164.
• Others have reported on various RNAi and gene-silencing systems. For example, Churikov et al. International PCT Publication No. WO 01/42443 describe certain methods for modifying genetic characteristics of an organism using certain dsRNAs. Reed et al. International PCT Publication No. WO 01/68836 describe certain methods for gene silencing in plants. Honer et al. International PCT Publication No. WO 01/70944 describe certain methods of drug screening using transgenic nematodes as Parkinson's Disease models using certain dsRNAs. Arndt et al. International PCT Publication No. WO 01/92513 describe certain methods for mediating gene suppression by using factors that enhance RNAi. Tuschl et al. International PCT Publication No. WO 02/44321 describe certain synthetic siRNA constructs. Pachuk et al. International PCT Publication No. WO 00/63364, and Satishchandran et al. International PCT Publication No. WO 01/04313 describe certain methods and compositions for inhibiting the function of certain polynucleotide sequences using certain long (over 250 bp), vector expressed dsRNAs. Kreutzer et al. International PCT Publications Nos. WO 02/055692, WO 02/055693, and EP 1144623 B1 describes certain methods for inhibiting gene expression using dsRNA. Graham et al. International PCT Publications Nos. WO 99/49029 and WO 01/70949, and AU 4037501 describe certain vector expressed siRNA molecules. Fire et al. U.S. Pat. No. 6,506,559 describe certain methods for inhibiting gene expression in vitro using certain long dsRNA (299 bp-1033 bp) constructs that mediate RNAi. Martinez et al. 2002 Cell, 110, 563-574 describe certain single-stranded siRNA constructs, including certain 5′-phosphorylated single-stranded siRNAs that mediate RNA interference in HeLa cells. Harborth et al. 2003 Anti-sense & Nucleic Acid Drug Development 13: 83-105 describe certain chemically and structurally modified siRNA molecules. Chiu and Rana 2003 RNA 9: 1034-1048 describe certain chemically and structurally modified siRNA molecules. Woolf et al. International PCT Publication Nos. WO 03/064626 and WO 03/064625 describe certain chemically modified dsRNA constructs.
• Kits for RNAi synthesis are commercially available, e.g., from New England Biolabs and Ambion.
• The RNAi agent(s) of the present disclosure target (e.g., bind to, anneal to, etc.) the Beta-Catenin mRNA. The use of the RNAi agent to Beta-Catenin results in a decrease of Beta-Catenin activity, level and/or expression, e.g., a “knock-down” or “knock-out” of the target gene or target sequence. Particularly, in one embodiment, in the case of a disease state characterized by over-expression or hyper-activity or improper cellular compartmentalization of Beta-Catenin, administration of a RNAi agent to Beta-Catenin knocks down the Beta-Catenin target enough to restore a normal level of Beta-Catenin activity.
• A suitable RNAi agent can be selected by any process known in the art or conceivable by one of ordinary skill in the art. For example, the selection criteria can include one or more of the following steps: initial analysis of the Beta-Catenin gene sequence and design of RNAi agents; this design can take into consideration sequence similarity across species (human, cynomolgus, mouse, etc.) and dissimilarity to other (non-Beta-Catenin) genes; screening of RNAi agents in vitro (e.g., at 10 nM in HeLa cells); determination of EC50 in HeLa cells; determination of viability of cells treated with RNAi agents, including insensitive cells which do not require Beta-Catenin for survival (e.g., NCI-H28 or RKO), or sensitive cells, which do require Beta-Catenin for survival (e.g., LoVo, DLD-1, LS411N, or SW403); testing with human PBMC (peripheral blood mononuclear cells), e.g., to test levels of TNF-alpha to estimate immunogenicity, wherein immunostimulatory sequences are less desired; testing in human whole blood assay, wherein fresh human blood is treated with an RNAi agent and cytokine/chemokine levels are determined [e.g., TNF-alpha (tumor necrosis factor-alpha) and/or MCP1 (monocyte chemotactic protein 1)], wherein Immunostimulatory sequences are less desired; determination of gene knockdown in vivo using Hep3B subcutaneous tumors in test animals; Beta-Catenin target gene modulation analysis, e.g., using a pharmacodynamic (PD) marker, for example, other components of the Wnt/Beta-Catenin pathway, wherein Beta-Catenin knockdown leads to a dose-dependent reduction of abundance of those components; and optimization of specific modifications of the RNAi agents.
• The dsRNA molecules (RNAi agents) described herein are thus useful in RNA interference of the Beta-Catenin gene.
• Features of a RNAi Agent: Sense Strand, Anti-Sense Strand and (Optional) Overhangs
• In various embodiments, the RNAi agents comprise a first strand and a second strand, e.g., a sense strand and an anti-sense strand. Optionally, one or both ends of the duplex contain unpaired nucleotides referred to herein as “overhangs”.
• The term “anti-sense strand” refers to the strand of a RNAi agent which includes a region that is substantially complementary to a target sequence. As used herein, the term “region of complementarity” refers to the region on the anti-sense strand that is substantially complementary to a sequence, for example a target sequence, as defined herein. Where the region of complementarity is not fully complementary to the target sequence, the mismatches may be in the internal or terminal regions of the molecule. Generally, the most tolerated mismatches are in the terminal regions, e.g., within 5, 4, 3, or 2 nucleotides of the 5′ and/or 3′ terminus.
• The term “sense strand,” as used herein, refers to the strand of a RNAi agent that includes a region that is substantially complementary to a region of the anti-sense strand as that term is defined herein.
• The sequence of a gene may vary from individual to individual, especially at wobble positions within the coding segment, or in the untranslated region; individuals may also differ from each other in coding sequence, resulting in additional differences in mRNA. The sequence of the sense and anti-sense strands of the RNAi agent can thus be designed to correspond to that of an individual patient, if and where needed. RNAi agents can also be modified in sequence to reduce immunogenicity, binding to undesired mRNAs (e.g., “off-target effects”) or to increase stability in the blood. These sequence variants are independent of chemical modification of the bases or 5′ or 3′ or other end-caps of the RNAi agents. In the case of Beta-Catenin, three human transcripts have been published: NP_001091679.1; NP_001091680.1; and NP_001895.1. Variants between these can be used to design RNAi agents to Beta-Catenin.
• The RNAi agents can comprise overhang(s), blunt end(s) and/or endcap(s). The RNAi agents can have overhangs of 0, 1, or 2 overhangs; in the case of 0 nt overhangs, they are blunt-ended. A RNAi agent can have 0, 1 or 2 blunt ends. In a “blunt-ended RNAi agent” both strands terminate in a base-pair; thus a blunt-ended molecule lacks either 3′ or 5′ single-stranded nucleotide overhangs.
• As used herein, the term “overhang” or “nucleotide overhang” refer to at least one unpaired nucleotide that protrudes from end of at least one of the two strands of the duplex structure of a RNAi agent. For example, when a 3′-end of one strand of a dsRNA extends beyond the 5′-end of the other strand, or vice versa, there is an overhang. A dsRNA can comprise an overhang of at least one nucleotide; alternatively the overhang can comprise at least two nucleotides, at least three nucleotides, at least four nucleotides, at least five nucleotides or more. An overhang can comprise or consist of a nucleotide/nucleoside analog, including a deoxynucleotide/nucleoside. The overhang(s) may be on the sense strand, the anti-sense strand or any combination thereof. Furthermore, the nucleotide(s) of an overhang can be present on the 5′ end, 3′ end or both ends of either an anti-sense or sense strand of a dsRNA.
• The RNAi agent can also optionally comprise a cap. The term “Cap” and the like include a chemical moiety attached to the end of a double-stranded nucleotide duplex, but is used herein to exclude a chemical moiety that is a nucleotide or nucleoside. A “3′ Cap” is attached at the 3′ end of a nucleotide or oligonucleotide and protects the molecule, e.g., from nucleases, such as those in blood serum or intestinal fluid. A useful 3′ cap will increase stability (e.g., reduce degradation, for example, by nucleases) and also still allow RNAi activity. Various 3′ end caps are as disclosed in, for example, WO 2005/021749 and WO 2007/128477; and U.S. Pat. Nos. 8,084,600 and 8,097,716. A “5′ cap” is attached at the 5′ end of a nucleotide or oligonucleotide. A cap should not interfere (or unduly interfere) with RNAi activity.
• The present disclosure thus contemplates a RNAi agent specific to Beta-Catenin comprising an anti-sense strand. In a more specific embodiment, the present disclosure contemplates a RNAi agent specific to Beta-Catenin comprising a first and a second strand, e.g., a sense strand and an anti-sense strand (which may optionally be contiguous or connected via a linker or loop), or an anti-sense strand and a sense strand (which may optionally be contiguous or connected via a linker or loop), which together comprise a double-stranded or complementary region, and can also optionally comprise one or two overhangs, and/or one or two caps, and/or modifications of the sugar, phosphate or base, and/or additional moieties. The RNAi agent is used to induce RNA interference of the Beta-Catenin gene.
• Target and Complementary Sequences
• The RNAi agents of the present disclosure target (e.g., specifically bind to, anneal to, etc.) the mRNA encoding the gene Beta-Catenin. The use of the RNAi agent specific to Beta-Catenin results in a decrease of Beta-Catenin activity, level and/or expression and/or cellular distribution/compartmentalization, e.g., a “knock-down” or “knock-out” of the target gene or target sequence. Particularly in one embodiment, in the case of a disease state characterized by over-expression or hyper-activity of Beta-Catenin, administration of a RNAi agent to Beta-Catenin knocks down the Beta-Catenin gene enough to restore a normal level, abundance or cellular distribution of Beta-Catenin activity.
• As used herein, “target sequence” or “target gene” refer to a contiguous portion of the nucleotide sequence of an mRNA molecule formed during the transcription of a gene, e.g., a Beta-Catenin gene, including mRNA that is a product of RNA processing of a primary transcription product. The target portion of the sequence will be at least long enough to serve as a substrate for iRNA-directed cleavage at or near that portion. For example, the target sequence will generally be from 9-36 nucleotides (nt) in length, e.g., 15-30 nucleotides in length, including all sub-ranges therebetween. As non-limiting examples, the target sequence can be from 15-30 nucleotides, 15-26 nucleotides, 15-23 nucleotides, 15-22 nucleotides, 15-21 nucleotides, 15-20 nucleotides, 15-19 nucleotides, 15-18 nucleotides, 15-17 nucleotides, 18-30 nucleotides, 18-26 nucleotides, 18-23 nucleotides, 18-22 nucleotides, 18-21 nucleotides, 18-20 nucleotides, 19-30 nucleotides, 19-26 nucleotides, 19-23 nucleotides, 19-22 nucleotides, 19-21 nucleotides, 19-20 nucleotides, 19 nucleotides, 20-30 nucleotides, 20-26 nucleotides, 20-25 nucleotides, 20-24 nucleotides, 20-23 nucleotides, 20-22 nucleotides, 20-21 nucleotides, 20 nucleotides, 21-30 nucleotides, 21-26 nucleotides, 21-25 nucleotides, 21-24 nucleotides, 21-23 nucleotides, or 21-22 nucleotides, 21 nucleotides, 22 nucleotides, or 23 nucleotides. The sense and anti-sense strands of the RNAi comprise a sequence complementary to that of the target nucleic acid, Beta-Catenin.
• As used herein, the term “strand comprising a sequence” refers to an oligonucleotide comprising a chain of nucleotides that is described by the sequence referred to using the standard nucleotide nomenclature.
• As used herein, and unless otherwise indicated, the term “complementary” refers to the ability of an oligonucleotide or polynucleotide comprising a first nucleotide sequence to hybridize and form a duplex structure under certain conditions with an oligonucleotide or polynucleotide comprising a second nucleotide sequence. Such conditions can, for example, be stringent, e.g., 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50° C. or 70° C. for 12-16 hours followed by washing. Other conditions, such as physiologically relevant conditions as may be encountered inside an organism, can apply. The skilled person will be able to determine the set of conditions most appropriate for a test of complementarity of two sequences in accordance with the ultimate application of the hybridized nucleotides.
• Complementary sequences within a RNAi agent, e.g., within a dsRNA as described herein, include base-paired oligonucleotides or polynucleotides comprising a first nucleotide sequence to an oligonucleotide or polynucleotide comprising a second nucleotide sequence over the entire length of one or both nucleotide sequences. Such sequences can be referred to as “fully complementary” with respect to each other herein. However, where a first sequence is referred to as “substantially complementary” with respect to a second sequence herein, the two sequences can be fully complementary, or they may form one or more, but generally not more than 5, 4, 3 or 2 mismatched base pairs upon hybridization for a duplex up to 30 base pairs, while retaining the ability to hybridize under the conditions most relevant to their ultimate application, e.g., inhibition of gene expression via a RISC pathway. However, where two oligonucleotides are designed to form, upon hybridization, one or more single-stranded overhangs, such overhangs shall not be regarded as mismatches with regard to the determination of complementarity. For example, a dsRNA comprising one oligonucleotide 21 nucleotides in length and another oligonucleotide 23 nucleotides in length, wherein the longer oligonucleotide comprises a sequence of 21 nucleotides that is fully complementary to the shorter oligonucleotide, may yet be referred to as “fully complementary” for the purposes described herein. The term “overhang” describes an unpaired nucleotide at the 3′ or 5′ end of a double-stranded nucleotide duplex, as described above. In one embodiment, the overhang is 1 to 4 nt long and is on the 3′ end.
• “Complementary” sequences, as used herein, may also include, or be formed entirely from, non-Watson-Crick base pairs and/or base pairs formed from non-natural and modified nucleotides, in as far as the above requirements with respect to their ability to hybridize are fulfilled. Such non-Watson-Crick base pairs includes, but are not limited to, G:U Wobble or Hoogstein base pairing.
• The terms “complementary,” “fully complementary” and “substantially complementary” herein may furthermore be used with respect to the base matching between the sense strand and the anti-sense strand of a dsRNA, or between the anti-sense strand of a RNAi agent and a target sequence, as will be understood from the context of their use. The RNAi agent of the present disclosure can comprise a sequence which is complementary to the sequence of a target sequence (DNA) which is disclosed herein. For example, if the target sequence disclosed is DNA, the RNAi agent can comprise a strand which is complementary to it (anti-parallel and having a sequence of bases which hydrogen bonds to the sequence of the target) and which is, for example, RNA, or RNA with a small number of DNA substitutions, or an alternative backbone such as FANA, PNA, GNA, TNA, boranophosphate or LNA, or RNA with a small number of substitutions which are FANA, PNA, GNA, TNA, boranophosphate or LNA, etc.
• As used herein, a polynucleotide that is “substantially complementary to at least part of” a messenger RNA (mRNA) refers to a polynucleotide that is substantially complementary to a contiguous portion of the mRNA of interest (e.g., an mRNA encoding Beta-Catenin). For example, a polynucleotide is complementary to at least a part of a Beta-Catenin mRNA if the sequence is substantially complementary to a non-interrupted portion of an mRNA encoding Beta-Catenin.
• Thus, the RNAi agent of the present disclosure is complimentary or substantially complimentary to a target sequence in the mRNA corresponding to the target gene Beta-Catenin and is double-stranded, comprising a sense and an anti-sense strand (which can be contiguous, linked via a loop, or otherwise joined), where the double-stranded region an be 9 to 36 bp long (particularly for example, 19 to 22 or 19 to 23 bp long), and can furthermore optionally comprise a 3′ or 5′ overhang, and the RNAi agent can furthermore comprise a 3′ cap. The RNAi agent mediates RNA interference, down-regulating or inhibiting the level, expression and/or activity of Beta-Catenin, and/or establishing or re-establishing an approximately normal level of Beta-Catenin and/or Beta-Catenin activity, or other biological function related to Beta-Catenin.
• Double-Stranded RNA
• The term “double-stranded RNA” or “dsRNA,” as used herein, refers to an RNAi agent comprising a first and a second strand; e.g., a composition that includes an RNA molecule or complex of molecules having a hybridized duplex region that comprises two anti-parallel and substantially complementary nucleic acid strands, which will be referred to as having “sense” and “antisense” orientations with respect to a target RNA. The antisense strand, with respect to the mRNA target, is also called the “guide” strand, and the sense strand is also called the “passenger” strand. The passenger strand can include at least one or more of the following: one or more extra nucleotides (e.g., a bulge or 1 nt loop) compared to the other strand, a nick, a gap, etc., compared to the other strand. In various embodiments, the first strand is the sense strand and the second strand is the anti-sense strand. In other embodiments, the first strand is the anti-sense strand, and the second strand is the sense strand.
• The duplex region can be of any length that permits specific degradation of a desired target RNA through a RISC pathway, but will typically range from 9 to 36 base pairs (“bp”) in length, e.g., 15-30 base pairs in length. Considering a duplex between 9 and 36 base pairs, the duplex can be any length in this range, for example, 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, or 36 bp and any sub-range therebetween, including, but not limited to 15-30 base pairs, 15-26 bp, 15-23 bp, 15-22 bp, 15-21 bp, 15-20 bp, 15-19 bp, 15-18 bp, 15-17 bp, 18-30 bp, 18-26 bp, 18-23 bp, 18-22 bp, 18-21 bp, 18-20 bp, 19-30 bp, 19-26 bp, 19-23 bp, 19-22 bp, 19-21 bp, 19-20 bp, 19 bp, 20-30 bp, 20-26 bp, 20-25 bp, 20-24 bp, 20-23 bp, 20-22 bp, 20-21 bp, 20 bp, 21-30 bp, 21-26 bp, 21-25 bp, 21-24 bp, 21-23 bp, 21-22 bp, 21 bp, 22 bp, or 23 bp. The dsRNAs generated in the cell by processing with Dicer and similar enzymes are generally in the range of about 19 to about 22 base pairs in length. One strand of the duplex region of a dsRNA comprises a sequence that is substantially complementary to a region of a target RNA. The two strands forming the duplex structure can be from a single RNA molecule having at least one self-complementary duplex region, or can be formed from two or more separate RNA molecules that hybridize to form the duplex. Where the duplex region is formed from two self-complementary regions of a single molecule, the molecule can have a duplex region separated by a single stranded chain of nucleotides (herein referred to as a “hairpin loop”, e.g., such as found in an shRNA construct) between the 3′-end of one strand and the 5′-end of the respective other strand forming the duplex structure. The hairpin loop can comprise at least one unpaired nucleotide; in some embodiments the hairpin loop can comprise at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 20, at least 23 or more unpaired nucleotides. Where the two substantially complementary strands of a dsRNA are comprised by separate RNA molecules, those molecules need not, but can be covalently connected. Where the two strands are connected covalently by a hairpin loop, the construct is generally referred to herein and in the art as a “shRNA”. Where the two strands are connected covalently by means other than a hairpin loop, the connecting structure is referred to as a “linker.” The term “siRNA” is also used herein to refer to a dsRNA as described above.
• RNAi Agents Lowering or Normalizing Beta-Catenin Level, Expression, Cellular Distribution, and/or Activity
• Example RNAi agents for targeting Beta-Catenin include those which bind to a mRNA corresponding to the Beta-Catenin gene provided herein. Example RNAi agents to Beta-Catenin are provided in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• Any method known in the art can be use to measure changes in Beta-Catenin activity, level, cellular distribution (e.g., localization to the membrane but not the cytoplasm or nucleus) and/or expression induced by a Beta-Catenin RNAi agent. Measurements can be performed at multiple timepoints, prior to, during and after administration of the RNAi agent, to determine the effect of the RNAi agent.
• The RNAi agents of the present disclosure silence, inhibit the expression of, down-regulate the expression of, and/or suppress the expression of the Beta-Catenin gene, such that an approximately normal level of Beta-Catenin activity, expression and/or level and/or distribution in various cellular compartments is achieved.
• In addition, in various embodiments, depending on the disease condition and biological context, it is acceptable to use the RNAi agents of the present disclosure to establish a level of Beta-Catenin expression, activity and/or level which is below the normal level, or above the normal level.
• Types of RNAi Agents and Modification Thereof
• The use of RNAi agents or compositions comprising an anti-sense nucleic acid to down-modulate the expression of a particular protein in a cell is well known in the art. A RNAi agent comprises a sequence complementary to, and is capable of hydrogen binding to, the coding strand of another nucleic acid (e.g., an mRNA). Thus, in various embodiments, the RNAi agents of the present disclosure encompass any RNAi agents which target (e.g., are complementary to, capable of specific hydrogen binding to, etc.) any sequences presented herein, e.g., in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• Anti-sense sequences complementary to an mRNA can be complementary to the coding region, the 5′ or 3′ untranslated region of the mRNA, and/or a region bridging the coding and untranslated regions, and/or portions thereof. Furthermore, a RNAi agent can be complementary to a regulatory region of the gene encoding the mRNA, for instance a transcription or translation initiation sequence or regulatory element. Particularly, a RNAi agent or any portion thereof can be complementary to a region preceding or spanning the initiation codon on the coding strand or in the 3′ untranslated region of an mRNA.
• RNAi agent molecules can be designed according to the rules of Watson and Crick base pairing. The RNAi agent can be complementary to the entire coding region of Beta-Catenin mRNA, but more particularly is an oligonucleotide which is anti-sense to only a portion of the coding or non-coding region of Beta-Catenin mRNA. For example, the anti-sense oligonucleotide can be complementary to the region surrounding the translation start site of Beta-Catenin mRNA. An anti-sense oligonucleotide can be, for example, about 5, 10, 15, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45 or 50 nucleotides in length.
• RNAi agent may have modifications internally, and/or at one or both ends. The modifications at the ends can help stabilize the RNAi agent, protecting it from degradation by nucleases in the blood.
• The RNAi agents can also optionally be designed to anneal to known or predicted exposed and/or single-stranded regions of the mRNA (e.g., loops).
• A RNAi agent can be constructed using chemical synthesis and enzymatic ligation reactions using procedures known in the art. For example, a RNAi agent can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to decrease off-target effects, and/or increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the anti-sense and sense nucleic acids, e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used.
• “G,” “C,” “A,” “T” and “U” each generally stand for a nucleotide that contains guanine, cytosine, adenine, thymidine and uracil as a base, respectively. However, the term “ribonucleotide” or “nucleotide” can also refer to a modified nucleotide or a surrogate replacement moiety. The skilled person is well aware that guanine, cytosine, adenine, and uracil may be replaced by other moieties without substantially altering the base pairing properties of an oligonucleotide comprising a nucleotide bearing such replacement moiety. For example, without limitation, a nucleotide comprising inosine as its base may base pair with nucleotides containing adenine, cytosine, or uracil. Hence, nucleotides containing uracil, guanine, or adenine may be replaced in the nucleotide sequences of dsRNA featured in the present disclosure by a nucleotide containing, for example, inosine. In another example, adenine and cytosine anywhere in the oligonucleotide can be replaced with guanine and uracil, respectively to form G-U Wobble base pairing with the target mRNA. Sequences containing such replacement moieties are suitable for the compositions and methods featured in the present disclosure.
• The skilled artisan will recognize that the term “RNA molecule” or “ribonucleic acid molecule” encompasses not only RNA molecules as expressed or found in nature (i.e., are naturally occurring), but also non-naturally-occurring analogs and derivatives of RNA comprising one or more ribonucleotide/ribonucleoside analogs or derivatives as described herein or as known in the art. Strictly speaking, a “ribonucleoside” includes a nucleoside base and a ribose sugar, and a “ribonucleotide” is a ribonucleoside with one, two or three phosphate moieties. However, the terms “ribonucleoside” and “ribonucleotide” can be considered to be equivalent as used herein. The RNA can be modified in the nucleobase structure or in the ribose-phosphate backbone structure, e.g., as described herein below. However, the molecules comprising ribonucleoside analogs or derivatives must retain the ability to form a duplex. As non-limiting examples, an RNA molecule can also include at least one modified ribonucleoside, including but not limited to a 2′-O-methyl modified nucleotide, a nucleoside comprising a 5′ phosphorothioate group, a terminal nucleoside linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group, a locked nucleoside, an abasic nucleoside, a 2′-deoxy-2′-fluoro modified nucleoside, a 2′-amino-modified nucleoside, 2′-alkyl-modified nucleoside, morpholino nucleoside, an unlocked ribonucleotide (e.g., an acyclic nucleotide monomer, as described in WO 2008/147824), a phosphoramidate or a non-natural base comprising nucleoside, or any combination thereof. Alternatively, an RNA molecule can comprise at least two modified ribonucleosides, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 20 or more, up to the entire length of the dsRNA molecule. The modifications need not be the same for each of such a plurality of modified ribonucleosides in an RNA molecule. In one embodiment, modified RNAs contemplated for use in methods and compositions described herein are peptide nucleic acids (PNAs) that have the ability to form the required duplex structure and that permit or mediate the specific degradation of a target RNA via a RISC pathway. In some cases, a RNA molecule can include a terminal dinucleotide (e.g., TT) which is DNA, and/or a small number of internal (e.g., base-pairing) DNA bases (e.g., fewer than the number of RNA bases), for example, a T substituting a U.
• Examples of modified nucleotides which can be used to generate the RNAi agent include 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracdihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3) w, and 2,6-diaminopurine.
• A “modified variant” of a sequence disclosed herein includes any variant comprising the same sequence, but with a modification in the base, sugar, phosphate or backbone (but not a base substitution, e.g., A for G, or C for U). Thus, a modified variant can comprise any modified nucleotide described above (e.g., 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, etc.). When a base is replaced by a corresponding modified base (e.g., A for modified A), these modified nucleotides do not constitute a mismatch or base difference. Thus a given sequence with a U at a particular position and a modified variant comprising a 5-fluorouracil, 5-bromouracil, 5-chlorouracil, or 5-iodouracil at the same sequence would differ by 0 nt (or have no mismatches); however, a given sequence with a C at a particular position and a different sequence with a 5-fluorouracil (wherein the two sequences are otherwise identical) would differ by 1 nt (1 mismatch).
• In one embodiment, the present disclosure encompasses any modified variant of any RNAi agent disclosed herein. The modified variant contains the same sequence, but can be modified to contain modifications in the phosphate, sugar, base, nucleotide, etc. For example, the modified variant can contain one or more of the modified nucleotides listed herein, for example a C replaced by a 2′-modified C (such sequences would differ by 0 mismatches).
• In one aspect, a modified ribonucleoside includes a deoxyribonucleoside. In such an instance, a RNAi agent can comprise one or more deoxynucleosides, including, for example, a deoxynucleoside overhang(s), or one or more deoxynucleosides within the double-stranded portion of a dsRNA. However, it is self-evident that under no circumstances is a double-stranded DNA molecule encompassed by the term “RNAi agent.”
• Replacing the 3′-terminal nucleotide overhanging segments of a 21-mer RNAi agent duplex having two-nucleotide 3′-overhangs with deoxyribonucleotides does not have an adverse effect on RNAi activity. Replacing up to four nucleotides on each end of the RNAi agent with deoxyribonucleotides has been well tolerated, whereas complete substitution with deoxyribonucleotides results in no RNAi activity. International PCT Publication No. WO 00/44914, and Beach et al. International PCT Publication No. WO 01/68836 preliminarily suggest that siRNA may include modifications to either the phosphate-sugar backbone or the nucleoside to include at least one of a nitrogen or sulfur heteroatom. Kreutzer et al. Canadian Patent Application No. 2,359,180, also describe certain chemical modifications for use in dsRNA constructs in order to counteract activation of double-stranded RNA-dependent protein kinase PKR, specifically 2′-amino or 2′-O-methyl nucleotides, and nucleotides containing a 2′-0 or 4′-C methylene bridge. Additional 3′-terminal nucleotide overhangs include dT (deoxythimidine), 2′-0,4′-C-ethylene thymidine (eT), and 2-hydroxyethyl phosphate (hp).
• Parrish et al. 2000 Molecular Cell 6: 1077-1087 tested certain chemical modifications targeting the unc-22 gene inC. elegansusing long (>25 nt) siRNA transcripts. The authors describe the introduction of thiophosphate residues into these siRNA transcripts by incorporating thiophosphate nucleotide analogs with T7 and T3 RNA polymerase and observed that RNAs with two phosphorothioate modified bases also had substantial decreases in effectiveness as RNAi. Further, Parrish et al. reported that phosphorothioate modification of more than two residues greatly destabilized the RNAs in vitro such that interference activities could not be assayed. Id. at 1081. The authors also tested certain modifications at the 2′-position of the nucleotide sugar in the long siRNA transcripts and found that substituting deoxynucleotides for ribonucleotides produced a substantial decrease in interference activity, especially in the case of Uridine to Thymidine and/or Cytidine to deoxy-Cytidine substitutions. Id. In addition, the authors tested certain base modifications, including substituting, in sense and anti-sense strands of the siRNA, 4-thiouracil, 5-bromouracil, 5-iodouracil, and 3-(aminoallyl) uracil for uracil, and inosine for guanosine. Whereas 4-thiouracil and 5-bromouracil substitution appeared to be tolerated, Parrish reported that inosine produced a substantial decrease in interference activity when incorporated in either strand. Parrish also reported that incorporation of 5-iodouracil and 3-(aminoallyl) uracil in the anti-sense strand resulted in a substantial decrease in RNAi activity as well.
• Those skilled in the art will appreciate that it is possible to synthesize and modify the siRNA as desired, using any conventional method known in the art (see Henschel et al. 2004 DEQOR: a web-based tool for the design and quality control of siRNAs. Nucleic Acids Research 32 (Web Server Issue): W113-W120). Further, it will be apparent to those skilled in the art that there are a variety of regulatory sequences (for example, constitutive or inducible promoters, tissue-specific promoters or functional fragments thereof, etc.) which are useful for the anti-sense oligonucleotide, siRNA, or shRNA expression construct/vector.
• There are several examples in the art describing sugar, base, phosphate and backbone modifications that can be introduced into nucleic acid molecules with significant enhancement in their nuclease stability and efficacy. For example, oligonucleotides are modified to enhance stability and/or enhance biological activity by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-O-methyl, 2′-O-allyl, 2′-H, nucleotide base modifications (for a review see Usman and Cedergren 1992 TIBS. 17: 34; Usman et al. 1994 Nucleic Acids Symp. Ser. 31: 163; Burgin et al. 1996 Biochemistry 35: 14090). Sugar modification of nucleic acid molecules are extensively described in the art.
• Additional modifications and conjugations of RNAi agents have been described. Soutschek et al. 2004 Nature 432: 173-178 presented conjugation of cholesterol to the 3′-end of the sense strand of a RNAi agent by means of a pyrrolidine linker, thereby generating a covalent and irreversible conjugate. Chemical modifications (including conjugation with other molecules) of siRNA may also be made to improve the in vivo pharmacokinetic retention time and efficiency.
• In various embodiments of the present disclosure, the RNAi agent to Beta-Catenin comprises at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide; at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide; and/or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• In various embodiments of the present disclosure, the RNAi agent comprises a 2′-modification selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• In another embodiment, the RNAi comprises a gap or missing base. For example, the phosphate-sugar backbone may be present, but the base missing.
• In another embodiment, the RNAi agent has a single-stranded nick (e.g., a break or missing bond in the backbone). In various embodiments, a single-stranded nick can be in either the sense or anti-sense strand, or both.
• This nick can be, for example, in the sense strand, producing a small internally segmented interfering RNA, or sisiRNA, which may have less off-target effects than the corresponding RNAi agent without a nick.
• The anti-sense nucleic acid or RNAi agent can also have an alternative backbone such as locked nucleic acid (LNA), Morpholino, peptidic nucleic acid (PNA), threose nucleic acid (TNA), or glycol nucleic acid (GNA), FANA, boranophosphate RNA, or be primarily RNA with a few nucleotides which are substituted by DNA, LNA, PNA, TNA, GNA, FANA, boranophosphate, or the like, and/or it can be labeled (e.g., radiolabeled or otherwise tagged).
• One or both strands can comprise an alternative backbone
• In yet another embodiment, the RNAi agent employed by the methods of the present disclosure can include an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. Gaultier et al. 1987 Nucleic Acids. Res. 15: 6625-6641. The RNAi agent can also comprise a 2′-o-methylribonucleotide (Inoue et al. 1987 Nucleic Acids Res. 15: 6131-6148) or a chimeric RNA-DNA analogue (Inoue et al. 1987 FEBS Lett. 215: 327-330).
• Alternatively, gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of Beta-Catenin (e.g., the promoter and/or enhancers) to form triple helical structures that prevent transcription of the Beta-Catenin gene. See generally, Helene 1991 Anticancer Drug Des. 6(6): 569-84; Helene et al. 1992 Ann. N.Y. Acad. Sci. 660: 27-36; and Maher 1992, Bioassays 14(12): 807-15.
• Production of RNAi Agents
• The RNAi agent can be produced biologically within a cell using an expression vector into which a nucleic acid has been subcloned in an anti-sense orientation (i.e., RNA transcribed from the inserted nucleic acid will be in an anti-sense orientation to a target nucleic acid of interest). The RNAi agent can also be produced biologically using an expression vector into which a nucleic acid has been subcloned as an shRNA construct (eg., RNA transcribed from the inserted nucleic acid will have a first region in an anti-sense orientation to a target nucleic acid of interest, a second region that comprises a loop or hinge, and a third region in a sense orientation to the target nucleic acid of interest, wherein the first and third regions of the transcript preferably hydribize to each other, thereby forming a stem-and-loop structure.
• Methods of producing RNAi agents are well-known in the art and available to persons of ordinary skill in the art.
• Kits for synthesis of RNAi are commercially available from, e.g., New England Biolabs and Ambion.
• Delivery of RNAi Agents
• RNAi agents of the present disclosure can be delivered or introduced (e.g., to a cell in vitro, to a test animal, or to a human) by any means known in the art.
• The RNAi agents of the present disclosure are typically administered to a subject or generated in situ such that they hybridize with cellular mRNA and/or genomic DNA encoding Beta-Catenin, and inhibit expression by inhibiting transcription and/or translation. An example of a route of administration of RNAi agents includes direct injection at a tissue site. Alternatively, RNAi agents can be modified to target selected cells and then administered systemically. For example, for systemic administration, anti-sense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface, e.g., by linking the anti-sense nucleic acid molecules to peptides or antibodies which bind to cell surface receptors or antigens. The anti-sense nucleic acid molecules can also be delivered to cells using vectors well known in the art and described in, for example, US20070111230. To achieve sufficient intracellular concentrations of the anti-sense molecules, vector constructs in which the anti-sense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.
• “Introducing into a cell,” when referring to a RNAi agent, means facilitating or effecting uptake or absorption into the cell, as is understood by those skilled in the art. Absorption or uptake of a RNAi agent can occur through unaided diffusive or active cellular processes, or by auxiliary agents or devices. The meaning of this term is not limited to cells in vitro; a RNAi agent may also be “introduced into a cell,” wherein the cell is part of a living organism. In such an instance, introduction into the cell will include the delivery to the organism. For example, for in vivo delivery, a RNAi agent can be injected into a tissue site or administered systemically. In vivo delivery can also be by a beta-glucan delivery system, such as those described in U.S. Pat. Nos. 5,032,401 and 5,607,677, and U.S. Publication No. 2005/0281781. In vitro introduction into a cell includes methods known in the art such as electroporation and lipofection. Further approaches are described herein below or known in the art.
• Delivery of RNAi agent to tissue is a problem both because the material must reach the target organ and must also enter the cytoplasm of target cells. RNA cannot penetrate cellular membranes, so systemic delivery of naked RNAi agent is unlikely to be successful. RNA is quickly degraded by RNAse activity in serum. For these reasons, other mechanisms to deliver RNAi agent to target cells has been devised. Methods known in the art include but are not limited to: viral delivery (retrovirus, adenovirus, lentivirus, baculovirus, AAV); liposomes (Lipofectamine, cationic DOTAP, neutral DOPC) or nanoparticles (cationic polymer, PEI), bacterial delivery (tkRNAi), electroporation, and also chemical modification (LNA) of siRNA to improve stability. Xia et al. 2002 Nat. Biotechnol. 20 and Devroe et al. 2002. BMC Biotechnol. 2 1: 15, disclose incorporation of siRNA into a viral vector. Porphysomes can also be used to deliver RNAi agents. Lovell et al. 2001 Nature Mater. 10: 324-32; and WO 2011/044671. Other systems for delivery of RNAi agents are contemplated and the RNAi agents of the present disclosure can be delivered by various methods yet to be found and/or approved by the FDA or other regulatory authorities. RNAi agents of the present disclosure can delivered in a suitable pharmaceutical composition. Several of these are described in greater detail, below.
• Pharmaceutical Compositions of RNAi Agents
• As used here, a “pharmaceutical composition” comprises a pharmaceutically effective amount of one or more Beta-Catenin RNAi agent, a pharmaceutically acceptable carrier, and, optionally, an additional disease treatment which works synergistically with the RNAi agent. The additional disease treatment can be additional RNAi agent(s) to Beta-Catenin, and/or additional RNAi agent(s) to another gene. As used herein, “pharmacologically effective amount,” “therapeutically effective amount” or simply “effective amount” refers to that amount of a RNAi agent effective to produce the intended pharmacological, therapeutic or preventive result. For example, if a given clinical treatment is considered effective when there is at least a 10% reduction in a measurable parameter associated with a disease or disorder, a therapeutically effective amount of a drug for the treatment of that disease or disorder is the amount necessary to effect at least a 10% reduction in that parameter. In this embodiment, a therapeutically effective amount of a RNAi agent targeting Beta-Catenin can reduce Beta-Catenin protein levels by at least 10%. In additional embodiments, a given clinical treatment is considered effective where there is at least a 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95% reduction in a measurable parameter associated with a disease or disorder, and the therapeutically effective amount of a drug for the treatment of that disease or disorder is the amount necessary to effect at least a 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95% reduction, respectively, in that parameter.
• The term “pharmaceutically acceptable carrier” refers to a carrier for administration of a therapeutic agent. Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. The term specifically excludes cell culture medium. For drugs administered orally, pharmaceutically acceptable carriers include, but are not limited to pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose, while corn starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatin, while the lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract. Agents included in drug formulations are described further herein.
• The pharmaceutical compositions comprising a Beta-Catenin RNAi agent can be in solid form, for example, powders, granules, tablets, pills, gelcaps, gelatin capsules, liposomes, suppositories, chewable forms, or patches. The pharmaceutical compositions comprising a Beta-Catenin RNAi agent can also be presented in liquid form, for example, solutions, emulsions, suspensions, elixirs, or syrups. Appropriate liquid supports can be, for example, water, organic solvents such as polyol, such as glycerol or glycols, including propylene glycol and polyethylene glycol, or ethanol, Cremophor EL, or mixtures thereof, in varying proportions, in water. The compositions can comprise nano-sized amorphous or crystalline granules coated with albumin or a surfactant.
• Appropriate supports can include, for example, antibacterial and antifungal agents, buffering agents, calcium phosphate, cellulose, methyl cellulose, chlorobutanol, cocoa butter, colorings, dextrin, emulsifiers, enteric coatings, flavorings, gelatin, isotonic agents, lecithin, magnesium stearate, perfuming agents, polyalcohols such as mannitol, injectable organic esters such as ethyl oleate, paraben, phenol sorbic acid, polyethylene glycol, polyvinylpyrrolidine, phosphate buffered saline (PBS), preserving agents, propylene glycol, sodium carboxymethylcellulose, sodium chloride, sorbitol, various sugars (including, but not limited to, sucrose, fructose, galactose, lactose and trehalose), starch, suppository wax, talc, vegetable oils, such as olive oil and corn oil, vitamins, wax, and/or wetting agents. For Beta-Catenin RNAi agents, a preferred support comprises dextran and water, e.g. 5% dextrose in water (D5W).
• The biologically inert portion of the pharmaceutical composition can optionally be erodible, allowing timed release of the RNAi agent.
• The pharmaceutical composition can comprise additional components which aid in delivery, stability, efficacy, or reduction of immunogenicity.
• Additional Components of a Pharmaceutical Composition Comprising a RNAi Agent to Beta-Catenin
• Additional components of a pharmaceutical composition comprising a RNAi Agent to Beta-Catenin can be added to aid in delivery, stability, efficacy, or reduction of immunogenicity.
• Liposomes have been used previously for drug delivery (e.g., delivery of a chemotherapeutic). Liposomes (e.g., cationic liposomes) are described in PCT publications WO02/100435A1, WO03/015757A1, and WO04029213A2; U.S. Pat. Nos. 5,962,016; 5,030,453; and 6,680,068; and U.S. Patent Application 2004/0208921. A process of making liposomes is also described in WO04/002453A1. Furthermore, neutral lipids have been incorporated into cationic liposomes (e.g., Farhood et al. 1995).
• Cationic liposomes have been used to deliver RNAi agent to various cell types (Sioud and Sorensen 2003; U.S. Patent Application 2004/0204377; Duxbury et al., 2004; Donze and Picard, 2002).
• Use of neutral liposomes disclosed in Miller et al. 1998, and U.S. Patent Application 2003/0012812.
• As used herein, the term “SNALP” refers to a stable nucleic acid-lipid particle. A SNALP represents a vesicle of lipids coating a reduced aqueous interior comprising a nucleic acid such as an iRNA or a plasmid from which an iRNA is transcribed. SNALPs are described, e.g., in U.S. Patent Application Publication Nos. 20060240093, 20070135372, and in International Application No. WO 2009082817.
• Chemical transfection using lipid-based, amine-based and polymer-based techniques, is disclosed in products from Ambion Inc., Austin, Tex.; and Novagen, EMD Biosciences, Inc, an Affiliate of Merck KGaA, Darmstadt, Germany); Ovcharenko D (2003) “Efficient delivery of siRNAs to human primary cells.” Ambion TechNotes 10 (5): 15-16). Additionally, Song et al. (Nat Med. published online (Fete 1 0, 2003) doi: 10.1038/nm828) and others [Caplen et al. 2001 Proc. Natl. Acad. Sci. (USA), 98: 9742-9747; and McCaffrey et al. Nature 414: 34-39] disclose that liver cells can be efficiently transfected by injection of the siRNA into a mammal's circulatory system.
• A variety of molecules have been used for cell-specific RNAi agent delivery. For example, the nucleic acid-condensing property of protamine has been combined with specific antibodies to deliver siRNAs. Song et al. 2005 Nat Biotech. 23: 709-717. The self-assembly PEGylated polycation polyethylenimine (PEI) has also been used to condense and protect siRNAs. Schiffelers et al. 2004 Nucl. Acids Res. 32: e149, 141-110.
• The siRNA-containing nanoparticles were then successfully delivered to integrin-overexpressing tumor neovasculature. Hu-Lieskovan et al. 2005 Cancer Res. 65: 8984-8992.
• The RNAi agents of the present disclosure can be delivered via, for example, Lipid nanoparticles (LNP); neutral liposomes (NL); polymer nanoparticles; double-stranded RNA binding motifs (dsRBMs); or via modification of the RNAi agent (e.g., covalent attachment to the dsRNA).
• Lipid nanoparticles (LNP) are self-assembling cationic lipid based systems. These can comprise, for example, a neutral lipid (the liposome base); a cationic lipid (for siRNA loading); cholesterol (for stabilizing the liposomes); and PEG-lipid (for stabilizing the formulation, charge shielding and extended circulation in the bloodstream).
• The cationic lipid can comprise, for example, a headgroup, a linker, a tail and a cholesterol tail. The LNP can have, for example, good tumor delivery, extended circulation in the blood, small particles (e.g., less than 100 nm), and stability in the tumor microenvironment (which has low pH and is hypoxic).
• Neutral liposomes (NL) are non-cationic lipid based particles.
• Polymer nanoparticles are self-assembling polymer-based particles.
• Double-stranded RNA binding motifs (dsRBMs) are self-assembling RNA binding proteins, which will need modifications.
• In various embodiments of the present disclosure, the RNAi agent to Beta-Catenin is ligated to one or more diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and transferrin.
• The RNAi agents of the present disclosure can be prepared in a pharmaceutical composition comprising various components appropriate for the particular method of administration of the RNAi agent.
• Administration of a Pharmaceutical Composition Comprising a RNAi Agent
• The pharmaceutical composition comprising a Beta-Catenin can be administered by buccal, inhalation (including insufflation and deep inhalation), nasal, oral, parenteral, implant, injection or infusion via epidural, intra-arterial, intra-articular, intra-capsular, intra-cardiac, intra-cerebroventricular, intracranial, intradermal, intramuscular, intra-orbital, ocular, intraperitoneal, intra-spinal, intrasternal, intrathecal, intravenous, subarachnoid, sub-capsular, subcutaneous, sub-cuticular, transendothelial, transtracheal, transvascular, rectal, sublingual, topical, and/or vaginal routes. This may be by injection, infusion, dermal patch, or any other method known in the art. The formulation can be powdered, nebulized, aerosolized, granulized or otherwise appropriately prepared for delivery. The administration, if liquid, may be slow or via bolus, though, under some circumstances known in the art, bolus injections may lead to loss of material through the kidneys.
• The pharmaceutical compositions comprising a Beta-Catenin RNAi agent can be administered with medical devices known in the art. For example, in a particular embodiment, a RNAi agent can be administered with a needle-less hypodermic injection device, such as the devices disclosed in U.S. Pat. Nos. 5,399,163, 5,383,851, 5,312,335, 5,064,413, 4,941,880, 4,790,824, or 4,596,556. Examples of well-known implants and modules useful in the present disclosure include: U.S. Pat. No. 4,487,603, which discloses an implantable micro-infusion pump for dispensing medication at a controlled rate; U.S. Pat. No. 4,486,194, which discloses a therapeutic device for administering medications through the skin; U.S. Pat. No. 4,447,233, which discloses a medication infusion pump for delivering medication at a precise infusion rate; U.S. Pat. No. 4,447,224, which discloses a variable flow implantable infusion apparatus for continuous drug delivery; U.S. Pat. No. 4,439,196, which discloses an osmotic drug delivery system having multi-chamber compartments; and U.S. Pat. No. 4,475,196, which discloses an osmotic drug delivery system. Many other such implants, delivery systems, and modules are known to those skilled in the art.
• In certain embodiments, the pharmaceutical compositions comprising a RNAi agent can be formulated to ensure proper distribution in vivo. Administration of a RNAi agent to Beta-Catenin can be systemic (whole-body) or, particularly, targeted to tissues or organs that express (or over-express or demonstrate a hyper-activity of) Beta-Catenin. Methods for targeting these particular tissues or organs are described herein, and/or are known in the art. For example, they can be formulated in liposomes. For methods of manufacturing liposomes, see, e.g., U.S. Pat. Nos. 4,522,811; 5,374,548; and 5,399,331. The liposomes may comprise one or more moieties which are selectively transported into specific cells or organs, thus enhance targeted drug delivery (see, e.g., V. V. Ranade (1989) J. Clin. Pharmacol. 29: 685).
• Example targeting moieties include folate or biotin (see, e.g., U.S. Pat. No. 5,416,016 to Low et al.); mannosides (Umezawa et al., (1988) Biochem. Biophys. Res. Commun. 153: 1038); antibodies (P. G. Bloeman et al. (1995) FEBS Lett. 357: 140; M. Owais et al. (1995) Antimicrob. Agents Chemother. 39: 180); surfactant protein A receptor (Briscoe et al. (1995) Am. J. Physiol. 1233: 134), different species of which may comprise the formulations of the present disclosures, as well as components of the invented molecules; p120 (Schreier et al. (1994) J. Biol. Chem. 269: 9090); see also K. Keinanen; M. L. Laukkanen (1994) FEBS Lett. 346: 123; J. J. Killion; I. J. Fidler (1994) Immunomethods 4: 273.
• The present disclosure thus encompasses pharmaceutical compositions comprising one or more RNAi agents to Beta-Catenin, which can optionally comprise various modifications and/or additional components, for use in treatment of Beta-Catenin-related diseases.
• Measuring the Effect of a RNAi Agent on Beta-Catenin Activity, Level, Expression or Compartmentalization
• Any method known in the art can be used to measure changes in Beta-Catenin activity, level, cellular distribution, and/or expression induced or altered by Beta-Catenin RNAi agent. Measurements can be performed at multiple timepoints, prior to, during and after administration of the RNAi agent, to determine the effect of the RNAi agent.
• The terms “silence,” “inhibit the expression of,” “down-regulate the expression of,” “suppress the expression of,” and the like, in so far as they refer to a Beta-Catenin gene, herein refer to the at least partial suppression of the expression of a Beta-Catenin gene, as manifested by a reduction of the amount of Beta-Catenin mRNA which may be isolated from or detected in a first cell or group of cells in which a Beta-Catenin gene is transcribed and which has or have been treated such that the expression of a Beta-Catenin gene is inhibited, as compared to a second cell or group of cells substantially identical to the first cell or group of cells but which has or have not been so treated (control cells). The degree of inhibition is usually expressed in terms of
• $\begin{array}{cc}\frac{\left(\mathrm{mRNA}\mathrm{in}\mathrm{control}\mathrm{cells}\right)-\left(\mathrm{mRNA}\mathrm{in}\mathrm{treated}\mathrm{cells}\right)}{\left(\mathrm{mRNA}\mathrm{in}\mathrm{control}\mathrm{cells}\right)}·100\%& \mathrm{Equation}1\end{array}$
• Alternatively, the degree of inhibition may be given in terms of a reduction of a parameter that is functionally linked to Beta-Catenin gene expression, e.g., the amount of protein encoded by a Beta-Catenin gene, etc. In principle, Beta-Catenin gene silencing may be determined in any cell expressing Beta-Catenin, either constitutively or by genomic engineering, and by any appropriate assay. However, when a reference or control is needed in order to determine whether a given RNAi agent inhibits the expression of the Beta-Catenin gene by a certain degree and therefore is encompassed by the instant disclosure, the assays provided in the Examples below shall serve as such reference.
• For example, in certain instances, expression of a Beta-Catenin gene is suppressed by at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by administration of a RNAi agent featured in the present disclosure. In some embodiments, a Beta-Catenin gene is suppressed by at least about 60%, 70%, or 80% by administration of a RNAi agent featured in the present disclosure. In some embodiments, a Beta-Catenin gene is suppressed by at least about 85%, 90%, or 95% or more by administration of a RNAi agent, as described herein.
• The ability of a RNAi agent to suppress Beta-Catenin can be first tested in vitro (e.g., using test cells such as HeLa cells).
• RNAi agents which can suppress Beta-Catenin in vitro can then be tested for immunostimulation using, for example, a PBMC (peripheral blood mononuclear cell) assay. RNAi agents can also be tested in animal tests. Test and control animals include those which over-express or under-express Beta-Catenin, as described in, for example, Chenn et al. 2003 Cer. Cortex 13: 599-606. RNAi agents which suppress or alter the level, activity and/or expression of Beta-Catenin can be used in medicaments to treat various Beta-Catenin-related diseases.
• By “lower” in the context of Beta-Catenin or a symptom of a Beta-Catenin-related disease is meant a statistically significant decrease in such level. The decrease can be, for example, at least 10%, at least 20%, 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 more. If, for a particular disease, or for an individual suffering from a particular disease, the levels or expression of Beta-Catenin are elevated, treatment with a Beta-Catenin RNAi agent of the present disclosure can particularly reduce the level or expression of Beta-Catenin to a level considered in the literature as within the range of normal for an individual without such disorder.
• The level or expression of Beta-Catenin can be measured by evaluation of mRNA (e.g., via Northern blots or PCR), or protein (e.g., Western blots). The effect of a RNAi agent on Beta-Catenin expression can be determined by measuring Beta-Catenin gene transcription rates (e.g., via Northern blots; or reverse transcriptase polymerase chain reaction or real-time polymerase chain reaction). Direct measurements can be made of levels of Beta-Catenin (which is expressed by the cell surface), e.g. by Western blots of tissues in which Beta-Catenin is expressed. The presence of Beta-Catenin in various cellular compartments (membrane, cytoplasm, and nucleus) can also be determined.
• As used herein, “down-regulates” refers to any statistically significant decrease in a biological activity and/or expression of Beta-Catenin, including full blocking of the activity (i.e., complete inhibition) and/or expression. For example, “down-regulation” can refer to a decrease of at least about 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100% in Beta-Catenin level, activity and/or expression.
• As used herein, the term “inhibit” or “inhibiting” Beta-Catenin refers to any statistically significant decrease in biological level, activity and/or expression of Beta-Catenin, including full blocking of the activity and/or expression. For example, “inhibition” can refer to a decrease of at least about 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100% in Beta-Catenin level, activity and/or expression. As used herein, the term “inhibit” similarly refers to a significant decrease in level, activity and/or expression, while referring to any other biological agent or composition.
• By “level”, it is meant that the Beta-Catenin RNAi agent can alter the level of Beta-Catenin, e.g., the level of Beta-Catenin mRNA or the level of Beta-Catenin protein, or the level of activity of Beta-Catenin.
• Some diseases, such as adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases, are characterized by excessive and/or mutated Beta-Catenin activity, and/or unusual Beta-Catenin distribution within the cell. Thus, in various embodiments, administration of a RNAi agent to Beta-Catenin particularly establishes or re-establishes a normal or approximately normal level of Beta-Catenin activity, expression, distribution, and/or level.
• By “normal” or “approximately normal” in terms of level, expression and/or activity, is meant at least: about 50%, about 60%, about 70%, about 80%, about 90%, and/or about 100%; and/or no more than: about 100%, about 120%, about 130%, about 140%, or about 150% of the level, expression or activity of Beta-Catenin in a healthy cellular compartment, cell, tissue, or organ. In one embodiment, administration of the appropriate amount of the appropriate Beta-Catenin RNAi agent restores Beta-Catenin level, activity and/or expression levels to about 50% to about 150%, more particularly about 60% to about 140%, more particularly to about 70% to about 130%, more particularly to about 80% to about 120%, more particularly to about 90% to about 110%, and most particularly to about 100% of that of a healthy cell, tissue or organ. Administration of a Beta-Catenin RNAi to a patient with a Beta-Catenin-related disease thus particularly restores the level, activity, and/or expression of Beta-Catenin to an approximately normal level, as determined by direct measurements of Beta-Catenin mRNA or protein levels, or indirect determinations, such as analyses of histological samples or levels of tissue samples. The RNAi agents of the present disclosure can also achieve a normal or approximately normal level of distribution of Beta-Catenin within the cell (e.g., in the membrane but not in the cytoplasm or nucleus).
• In some Beta-Catenin-related cancers, Beta-Catenin is required for tumor growth but is not amplified, over-expressed or mis-localized. A reduction in Beta-Catenin expression, level or activity should thus limit tumor growth. The disclosure thus encompasses methods wherein Beta-Catenin expression, level or activity is reduced to an expression, level or activity which is lower than normal.
• In addition, in various embodiments, depending on the disease condition and biological context, it is acceptable to use the RNAi agents of the present disclosure to establish a level of Beta-Catenin expression, activity and/or level which is below the normal level, or above the normal level.
• Beta-Catenin-Related Diseases
• The present disclosure encompasses RNAi agents to Beta-Catenin and administration of the RNAi agents to humans and non-human animals to treat various Beta-Catenin-related diseases.
• By “Beta-Catenin-related disease” is meant any disease related to a mutation and/or dysfunction in the level, expression, cellular location, and/or activity of Beta-Catenin, and/or any disease which can be treated, prevented and/or ameliorated by modulating the level, expression, cellular location, and/or activity of Beta-Catenin. In some cases, the “Beta-Catenin-related disease” includes cancers wherein Beta-Catenin is required for tumor growth but is not amplified, over-expressed or mis-localized. A reduction in Beta-Catenin expression, level or activity should thus limit tumor growth. In various embodiments of the present disclosure, a Beta-Catenin-related disease can be treated and/or ameliorated by a RNAi agent to Beta-Catenin.
• Beta-Catenin-related diseases are often associated with aberrations in the canonical Wnt/Beta-Catenin pathway. Wnt signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues. In the Wnt pathway, when Wnt receptor complexes are not bound by ligand, the serine/threonine kinases, CK1 and GSK3α/β, phosphorylate Beta-Catenin. Phosphorylated Beta-Catenin is recognized by the F box/WD repeat protein β-TrCP, a component of a dedicated E3 ubiquitin ligase complex. Following ubiquitination, Beta-Catenin is targeted for rapid destruction by the proteosome. In the nucleus, the binding of Groucho to TCF (T cell factor) inhibits the transcription of Wnt target genes, including proto-oncogene c-myc. However, Beta-Catenin accumulation in the nucleus can lead to activation of these Wnt target genes. For example, once bound by Wnt, the Frizzled (Fz)/LRP co-receptor complex activates the canonical signaling pathway. Fz interacts with Dsh, a cytoplasmic protein that functions upstream of Beta-Catenin and the kinase GSK3β. Wnt signaling controls phosphorylation of LRP by GSK3β and casein kinase I-γ (CK1γ), thus regulating the docking of Axin. The recruitment of Axin away from the destruction complex leads to the stabilization of beta-catenin in the cytoplasm. Once in the nucleus, Beta-Catenin displaces Groucho from TCF/LEF to promote the transcription of Wnt target genes, including c-myc. Moon et al. 2002 science 296: 1644-1646; Nelson et al. 2004 Science 303: 1483-1487; and Clevers 2006 Cell 127: 469-480; and references cited therein.
• Beta-Catenin-related diseases are thus often associated with a mutated form of the protein, and/or an elevated level of mutant or wild-type Beta-Catenin, and/or presence of Beta-Catenin in cytoplasm and/or nucleus. In normal gastric mucosa, Beta-Catenin is localized to the cell membrane. Clements et al. 2002 Cancer Res. 62: 3503-6. As noted above, in the absence of growth or differentiation signals, cytoplasmic Beta-Catenin is rapidly turned over, under the control of the APC (adenomatous polyposis coli) protein and GSK-3P. Beta-Catenin accumulates in the cytoplasm in some cancer cells, chronic wounds and other diseased cells and tissues. Nuclear translocation can also occur. Beta-Catenin accumulation can result in interaction with the T-cell factor 4 or lymphoid-enhancer factor family of transcriptional activators, and can result in the activation of some developmentally-related genes and/or proto-oncogenes, including c-myc. Behrens et al. 1996 Nature 382: 638-642; and He et al. 1998 Science 281: 1509-1512.
• As noted above, Beta-Catenin turnover occurs in the proteosome, where Beta-Catenin is degraded after targeted phosphorylation of highly-conserved Ser and Thr residues (Ser33, Ser37, Thr41, and Ser45) and ubiquitination in the NH₂terminus. Mutations in these Ser and Thr residues result in accumulated Beta-Catenin and are associated with various cancers. A Ser37 to Phe37 mutation, at a mutational hotspot, is associated with Beta-Catenin accumulation and increased half-life in the SK23 mel (melanoma) cell line. Rubinfeld et al. 1997 Science 275: 1790-1792. A Ser45 to Tyr45 mutation in the 624 mel cell line also increased the half-life of Beta-Catenin. Rubinfeld et al. 1997. Other deletions and mutations of these residues resulting in Beta-Catenin accumulation are described in Funayama et al. 1995 J. Cell Biol. 128: 959; Munemitsu et al. 1996 Mol. Cell. Biol. 16: 4088; Yost et al. 1996 Genes Dev. 10: 1443; and Ha et al. 2002 Acta Derm. Venereol. 82: 428-431. Altered phosphorylation of Beta-Catenin is also associated with breast cancer. Sommers et al. 1994 Cancer Res. 54: 3544-3552.
• Beta-Catenin mutations outside the four Ser and Thr residues have also been associated with disease states. A nearby mutation of Aspartic acid 32 to Tyr was detected in a prostate cancer cell line. Voeller et al. 1998 Cancer Res. 58: 2520-2523. The 321-bp deletion from +82 to +402 was found in the HSC-39 gastric cancer cell line, Kawanishi et al. 1995 Mol. Cell. Biol. 15: 1175-1181. Other mutations at positions 32, 33, 34, 37 and 41 have been associated with pilomatrixomas (skin tumors of unknown origin and aetiology). Chan et al. 1999 Nature Genet. 21: 410-413. Additional mutations associated with gastric cancer were found at positions 8, 11, 13, 21, 24, 25, 28, 29, 32, 37, 39, 47, 48 and 55. Clements et al. 2002 Cancer Res. 62: 3503-3506. Various mutations in colorectal tumors are described in Miyaki et al. 1999 Cancer Res. 59: 4506-4509. All in all, mutations of Beta-Catenin at positions 8, 11, 13, 21, 24, 25, 28, 29, 32, 33, 34, 37, 39, 41, 45, 47, 48 and 55 have been associated with various cancers and other disease states.
• In addition, a 321-bp deletion from +82 to +402 occurs in HSC-39 gastric cancer cell line, Kawanishi et al. 1995 Mol. Cell. Biol. 15: 1175-1181. Additional Beta-Catenin mutations (inside and outside the region of the four Ser and Thr residues) have been associated with medulloblastoma, endometroid ovarian carcinoma, uterine endometrial carcinoma, hepatocellular carcinoma, and prostatic adenocarcinoma. Zurawel et al. 1998 Cancer Res. 58: 896-899; Palacios et al. 1998 Cancer Res. 58: 1344-1347; Fukuchi et al. 1998 Cancer Res. 58: 3526-3528; Miyoshi et al. 1998 Cancer Res. 58: 2524-2527; Voeller et al. 1998 Cancer Res. 2520-2523; and Iwao et al. 1998 Cancer Res. 58: 1021-1026; and Garcia-Rostan et al. 1999 Cancer Res. 59: 1811-1815.
• Alterations in the genetic or biochemical context can also alter Beta-Catenin level or activity. Excess intracellular Beta-Catenin is expressed in colon and other cancer cells with a defective APC. Munemitsu et al. 1995 Proc. Natl. Acad. Sci. USA 92:3046. A reduced cell-cell adhesion is caused by tyrosine-phosphorylation of Beta-Catenin with v-src gene transfection. Behrens et al. 1993 J. Cell Biol. 120: 757-766; Hamaguchi et al. 1993 EMBO J. 12:307-314; Matsuyoshi et al. 1992 J. Cell Biol. 118: 703-714.
• In addition, the term “Beta-Catenin-related disease” includes those diseases in which Beta-Catenin (in normal form, mutant form, and/or in an elevated level of normal or mutant form and/or altered localization within the cell) directly or indirectly causes an increase in expression, level or activity of a factor involved in a disease state; for example, nuclear beta-catenin activates production of c-myc, which is involved in several diseases. In addition, “Beta-Catenin-related disease” includes those diseases related to aberrations in the Wnt/Beta-Catenin pathway. For example, abnormalities of the Wnt/Beta-Catenin pathway are associated with various cancers, osteoporosis, ageing, oligodontia, and degenerative diseases. Clevers et al. 2006 Cell 127: 469-480; Moon et al. 2004 Nat. Rev. Genet. 5: 691-701; He et al. 2004 Develop. 131: 1663-1677; Logan et al. 2004 Ann. Rev. Cell. Dev. Biol. 20: 781-810. In addition, Wilms tumors (a pediatric kidney cancer) are sometimes associated with mutations in the WTX gene, a tumor suppressor gene which has recently been discovered to be involved in the Wnt/Beta-Catenin pathway. Huang et al. 2008. Curr. Opin. Cell Biol. 20: 119-125.
• In particular, the term “Beta-Catenin-related disease” includes adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing. See: Delektorskaya et al. 2008. Bull. Exp. Biol. Med. 146: 616-619; Li et al. 2005 World J. Gastroent. 11: 2117-23; Liu et al. 2010 J. Dental Res. 89: 318-330; Noda et al. 1009 Br. J. Cancer 100: 1647-1658; Saegusa et al. 2009 Am. J. Pathol. 174: 2107-2115; Saldanha et al. Br. J. Dermatol. 151: 157-64; Stojadinovic et al. Am. J. Pathol. 167: 59-69; Thompson et al. 2007 Hepatology 45: 1298-305; Wang et al. 2008 Cancer Epidemiol. Biomarkers Prev. 17: 2101-8.
• RNAi agents to Beta-Catenin can be used to treat Beta-Catenin-related diseases, particularly those diseases associated with altered expression, activity, compartmentalization, and/or levels of Beta-Catenin, or wherein Beta-Catenin is required for disease progression (e.g., tumor growth).
• RNAi Agents to Beta-Catenin for Treatment of Beta-Catenin-Related Diseases
• The RNAi agents to Beta-Catenin described herein can be formulated into pharmaceutical compositions which can be administered to humans or non-human animals. These compositions can comprise one or more RNAi agents, and, optionally, additional treatments useful for treating Beta-Catenin-related diseases. They can be administered as part of an early/preventative treatment, and can be administered in a therapeutically-effective dosage. The pharmaceutical composition can comprise a pharmaceutical carrier and can be administered by any method known in the art. These various aspects of the present disclosure are described in additional detail below.
• RNAi agents to Beta-Catenin can be administered to humans and non-human animals for treatment of Beta-Catenin-related diseases.
• In one embodiment of the present disclosure, the compositions comprising a Beta-Catenin RNAi agent can be administered to non-human animals. For example, the compositions can be given to chickens, turkeys, livestock animals (such as sheep, pigs, horses, cattle, etc.), companion animals (e.g., cats and dogs) and can have efficacy in treatment of adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing and similar and related diseases. In each case, the RNAi agent to Beta-Catenin would be selected to match the sequence of the Beta-Catenin of the genome of the animal, and to, particularly, contain at least 1 nt mismatch from all other genes in that animal's genome. The RNAi agents of the present disclosure can thus be used in treatment of Beta-Catenin-related diseases in humans and non-human animals.
• As used herein in the context of Beta-Catenin expression, the terms “treat,” “treatment,” and the like, refer to relief from or alleviation of pathological processes mediated by Beta-Catenin expression. In the context of the present disclosure insofar as it relates to any of the other conditions recited herein below (other than pathological processes mediated by Beta-Catenin expression), the terms “treat,” “treatment,” and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression or anticipated progression of such condition.
• By “treatment” is also meant prophylaxis, therapy, cure, or any other change in a patient's condition indicating improvement or absence of degradation of physical condition. By “treatment” is meant treatment of Beta-Catenin-related disease (e.g., adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases), or any appropriate treatment of any other ailment the patient has. As used herein, the terms “treatment” and “treat” refer to both prophylactic or preventative treatment and curative or disease-modifying treatment, including treatment of patients at risk of contracting a disease or suspected of having a disease, as well as patients already ill or diagnosed as suffering from a condition. The terms “treatment” and “treat” also refer to the maintenance and/or promotion of health in an individual not suffering from a disease but who may be susceptible to developing an unhealthy condition. In one embodiment, “treatment” does not encompass prevention of a disease state. Thus, the present disclosure is useful for suppressing expression of the Beta-Catenin gene and/or treating a Beta-Catenin-related disease in an individual afflicted by a Beta-Catenin-related disease, or an individual susceptible to a Beta-Catenin-related disease. An individual “afflicted” by a Beta-Catenin-related disease has demonstrated detectable symptoms characteristics of the disease, or had otherwise been shown clinically to have been exposed to or to carry Beta-Catenin-related disease pathogens or markers. As non-limiting examples, an individual afflicted by a Beta-Catenin-related disease can show outward symptoms; or can show no outward symptoms but can be shown with a clinical test to carry protein markers associated with a Beta-Catenin-related disease, or proteins or genetic material associated with a pathogen in the blood.
• Treatment of some Beta-Catenin-related diseases may be more efficacious if administered early rather than later. Thus, in one particular embodiment, the RNAi agent to Beta-Catenin is administered early, prior to disease manifestation, and/or as a preventative agent, rather than administered after disease establishment.
• Additional Treatments Used in Addition to or in Conjunction with RNAi Agents to Beta-Catenin
• Treatments of Beta-Catenin-related diseases can thus comprises various treatments, comprising a Beta Beta-Catenin RNAi agent, and optionally further comprising an additional treatment, which can be a method (or procedure), and/or an additional composition (e.g., an agent or additional RNAi agent).
• Beta-Catenin-related diseases include adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases. The use of known treatments for any of these diseases is within the capabilities of one of ordinary skill in the art. Any such additional treatment can be used in conjunction with a RNAi agent to Beta-Catenin.
• These additional treatments, which can be administered prior to, simultaneously, or after administration of the RNAi agent(s) to Beta-Catenin, include: 5-fluoro-29-deoxyuridine, 7-hydroxystaurosporine, a goserlin implant, antibiotic, bevacizumab, bicalutamide, bleomycin, camptothecin, carboplatin, cetuximab, cisplatin, colcemid, Cycloheximide, cyclophosphamide, cytarabine, cytosine arabinoside (Ara-C), dacarbazine, docetaxel, doxorubicin, edelfosine, ehlorambucil, epipodophyllotoxin, epirubicin, erlotinib, estramustine, etoposide, fenretinide, finasteride, flavopiridol, fludarabine, fluorouracil, gefitinib, gemeitabine, goserelin, hexamethylmelamine, hydroxyurea, ifosfamide, irinotecan, L-asparaginase, leuprolide, meiphalan, mercaptopurine, methotrexate, mitixantrone, mitomycin, mitoxantrone, nitrogen mustard, octreotide, paclitaxel, pirubicin, Puromycin, sargramostim, staurosporine, steroids, tamoxifen, Taxol, tegafur, teniposide, topotecan, trastuzumab, UFT, 1-Hydroxy-2-imidazol-1-yl-phosphonoethyl) phosphonic acid monohydrate (sold under the tradename Zometa® by Novartis), 2-chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)-benzamide (also known as GDC-0449, and described in PCT Publication No. WO 06/028958), GDC 0941 (PCT Publication Nos. WO 09/036082 and WO 09/055730), BEZ 235 or NVP-BEZ 235 (PCT Publication No. WO 06/122806), ABT-263 (PCT Publication No. WO 09/155386), 5-azacitidine (sold under the tradename Vidaza®), decitabine (sold under the tradename Dacogen®), 6-thioguanine (sold under the tradename Purinethol®), pemetrexed (sold under the tradename Alimta®), Afutuzumab (available from Roche®), pegfilgrastim (sold under the tradename Neulasta® by Amgen), lenalidomide (also known as CC-5013 sold under the tradename Revlimid®), thalidomide (sold under the tradename Thalomid®), Alemtuzumab (sold under the tradename Campath®), Alitretinoin (sold under the tradename Panretin®), tretinoin (all-trans retinoic acid, also known as ATRA sold under the tradename Vesanoid®), Isotretinoin, bexarotene (sold under the tradename Targretin®), Alvocidib (U.S. Pat. No. 5,621,002), Amifostine (sold under the tradename Ethyol®), leucovorin, aminoglutethimide (sold under the tradename Cytadren®), Anagrelide (sold under the tradename Agrylin®), Anti-nausea drugs, Arsenic trioxide (sold under the tradename Trisenox®), asparaginase (also known as L-asparaginase, Erwinia L-asparaginase sold under the tradenames Elspar® and Kidrolase®), axitinib, bacillus calmette-guerin (sold under the tradenames theraCys® and TICE® BCG), denileukin diftitox (sold under the tradename Ontak®), Bortezomib (sold under the tradename Velcade®), Brivanib Alaninate ((S)—((R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate, also known as BMS-582664), Cabazitaxel (1-hydroxy-7β,10β-dimethoxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl-4-acetate-2-benzoate-13-[(2R,3 S)-3-{[(tert-butoxy) carbonyl]amino}-2-hydroxy-3-phenylpropanoate), larotaxel ((2α,3ξ,4α,5β,7α,10β,13α)-4,10-bis(acetyloxy)-13-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydroxy-9-oxo-5,20-epoxy-7,19-cyclotax-11-en-2-yl benzoate), Capecitabine (sold under the trademark Xeloda® by Roche), Casopitant (sold under the tradenames Rezonic® and Zunrisa® by GlaxoSmithKline), Cervarix® sold by GlaxoSmithKline, Gardasil® sold by Merck, cladribine (also known as 2-chlorodeoxyadenosine (2-CdA) sold under the tradename Leustatin™) Claribine (2-chlorodeoxyadenosine sold under the tradename Leustatin®), Dacetuzumab (also known as SGN-40 or huS2C6, available from Seattle Genetics, Inc), Darbepoetin alfa (sold under the tradename Aranesp® by Amgen), daunorubicin, decitabine (sold under the tradename Dacogen®), Deferasinox (sold under the tradename Exjade® by Novartis), Denosumab (sold under the tradename Prolia® by Amgen), Dulanermin (also known as AMG-951, available from Amgen/Genentech), Elotuzumab (HuLuc63, CAS No. 915296-00-3), Eltrombopag (sold under the tradenames Promacta® and Revolade® by GlaxoSmithKline), etoposide (also known as VP-16 and Etoposide phosphate sold under the tradenames Toposar®, VePesid® and Etopophos®), teniposide (also known as VM-26 sold under the tradename Vumon®), Exemestane (sold under the trademark Aromasin® by Pfizer), letrozole (sold under the tradename Femara® by Novartis), anastrozole (sold under the tradename Arimidex®), Figitumumab (also known as CP-751,871, available from ACC Corp), robatumumab (CAS No. 934235-44-6), Filgrastim (sold under the tradename Neupogen® by Amgen), floxuridine (sold under the tradename FUDR®), Fluoxymesterone (sold under the tradename Halotestin®), Fulvestrant (sold under the tradename Faslodex®), Gefitnib (sold under the tradename Iressa®), N44-[(3-Chloro-4-fluorophenyl)amino]-7-[[(3 “S”)-tetrahydro-3-furanyl]oxy-6-quinazolinyl]-4 (dimethylamino)-2-butenamide sold under the tradename Tovok® by Boehringer Ingelheim), Gemtuzumab ozogamicin (sold under the tradename Mylotarg® by Pfizer/Wyeth), Hydrocortisone (also known as cortisone, hydrocortisone sodium succinate, hydrocortisone sodium phosphate, and sold under the tradenames Ala-Cort®, Hydrocortisone Phosphate, Solu-Cortef®, Hydrocort Acetate® and Lanacort®), dexamethazone ((8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one), prednisolone (sold under the tradenames Delta-Cortel®, Orapred®, Pediapred® and Prelone®), prednisone (sold under the tradenames Deltasone®, Liquid Red®, Meticorten® and Orasone®), methylprednisolone (also known as 6-Methylprednisolone, Methylprednisolone Acetate, Methylprednisolone Sodium Succinate sold under the tradenames Duralone®, Medralone®, Medrol®, M-Prednisol® and Solu-Medrol®), Ibritumomab tiuxetan (sold under the tradename Zevalin®), idarubicin (sold under the tradenames Idamycin®, Idamycin PFS®), Inotuzumab ozogamicin (also referred to as CMC-544 and WAY-207294, available from Hangzhou Sage Chemical Co., Ltd.), interleukin-2 (also known as aldesleukin and IL-2 sold under the tradename Proleukin®), interleukin-11 (also known as oprevelkin sold under the tradename Neumega®), alpha interferon alfa (also known as IFN-alpha sold under the tradenames Intron® A, and Roferon-A®), Irinotecan (sold under the trademark Camptosar® by Pfizer), topotecan hydrochloride (sold under the tradename Hycamtin® by GlaxoSmithKline), Ixabepilone (sold under the tradename Lxempra® by Bristol-Myers Squibb), lapatinib or lapatinib ditosylate (sold under the trademark Tykerb® by GlaxoSmithKline), Leuprolide or leuprolide acetate (sold under the tradenames Viadure® by Bayer AG, Eligard® by Sanofi-Aventis and Lupron® by Abbott Lab), Linifanib (N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N′-(2-fluoro-5-methylphenyl)urea, also known as ABT 869, available from Genentech), sunitinib malate (sold under the tradename Sutent® by Pfizer), bosutinib (4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile, also known as SKI-606, and described in U.S. Pat. No. 6,780,996), dasatinib (sold under the tradename Sprycel® by Bristol-Myers Squibb), armala (also known as pazopanib sold under the tradename Votrient® by GlaxoSmithKline), imatinib and imatinib mesylate (sold under the tradenames Gilvec® and Gleevec® by Novartis), megestrol (also known as megestrol acetate sold under the tradename Megace®), motesanib (N-(2,3-dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide, and described in PCT Publication No. WO 02/066470), pasireotide (also known as SOM230, and described in PCT Publication No. WO 02/010192), sorafenib (sold under the tradename Nexavar®), nelarabine ((2R,3S,4R,5R)-2-(2-amino-6-methoxy-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol sold under the tradenames Arranon® and Atriance® by GlaxoSmithKline), neratinib (also known as HKI-272, (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxy quinolin-6-yl]-4-(dimethylamino)but-2-enamide, and described PCT Publication No. WO 05/028443), nilotinib hydrochloride (sold under the tradename Tasigna® by Novartis), Nilutamide (sold under the tradenames Nilandron® and Anandron®), bicalutamide (sold under tradename Casodex®), flutamide (sold under the tradename Fulexin™), N-methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]sulfanyl]benzamide, also known as AG013736, and described in PCT Publication No. WO 01/002369, octreotide (also known as octreotide acetate sold under the tradenames Sandostatin® and Sandostatin LAR®), Odanacatib (also know as MK-0822, N-(1-cyanocyclopropyl)-4-fluoro-N²-{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)biphenyl-4-yl]ethyl}-L-leucinamide, available from Lanzhou Chon Chemicals, ACC Corp., and ChemieTek, and described in PCT Publication no. WO 03/075836), oprelvekin (sold under the tradename Neumega® by Pfizer/Wyeth), oxaliplatin (sold under the tradename Eloxatin® ay Sanofi-Aventis and described in U.S. Pat. No. 4,169,846), Palifermin (sold under the tradename Kepivance® by Amgen), Pamidronate (sold under the tradename Aredia®), zoledronic acid (sold under the tradename Zometa®), panitumumab (sold under the tradename Vectibix® by Amgen), pentostatin (sold under the tradename Nipent®), Pertuzumab (sold under the trademark Omnitarg®, by Genentech), Raloxifene (sold under the tradename Evista®), Rituximab (sold under the trademarks Riuxan® and MabThera® by Genentech/Roche), Romiplostim (sold under the tradename Nplate® by Amgen), tamoxifen (sold under the tradename Novaldex®), Tanespimycin (17-allylamino-17-demethoxygeldanamycin, also known as KOS-953 and 17-AAG, available from SIGMA, and described in U.S. Pat. No. 4,261,989), Temozolomide (sold under the tradenames Temodar® and Temodal® by Schering-Plough/Merck), dactinomycin (also known as actinomycin-D and sold under the tradename Cosmegen®), melphalan (also known as L-PAM, L-sarcolysin, and phenylalanine mustard sold under the tradename Alkeran®), altretamine (also known as hexamethylmelamine (HMM) sold under the tradename Hexalen®), carmustine (sold under the tradename BiCNU®), bendamustine (sold under the tradename Treanda®), busulfan (sold under the tradenames Busulfex® and Myleran®), carboplatin (sold under the tradename Paraplatin®), lomustine (also known as CCNU sold under the tradename CeeNU®), cisplatin (also known as CDDP sold under the tradenames Platinol® and Platinol®-AQ), chlorambucil (sold under the tradename Leukeran®), cyclophosphamide (sold under the tradenames Cytoxan® and Neosar®), dacarbazine (also known as DTIC, DIC and imidazole carboxamide sold under the tradename DTIC-Dome®), altretamine (also known as hexamethylmelamine (HMM) sold under the tradename Hexalen®), ifosfamide (sold under the tradename Ifex®), procarbazine (sold under the tradename Matulane®), mechlorethamine (also known as nitrogen mustard, mustine and mechloroethamine hydrochloride sold under the tradename Mustargen®), streptozocin (sold under the tradename Zanosar®), thiotepa (also known as thiophosphoamide, TESPA and TSPA sold under the tradename Thioplex®, Temsirolimus (sold under the tradename Torisel® by Pfizer), ridaforolimus (formally known as deferolimus, (1R,2R,4S)-4-[(2R)-2 [(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28Z,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.310^4,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl dimethylphosphinate, also known as AP23573 and MK8669, and described in PCT Publication No. WO 03/064383), everolimus (sold under the tradename Afinitor® by Novartis), Toremifene (sold under the tradename Fareston®), tositumomab (sold under the trademarks Bexxar® by GlaxoSmithKline), ofatumumab (sold under the trademark Arzerra® by GlaxoSmithKline), Tremelimumab (IgG2 monoclonal antibody available from Pfizer, formerly known as ticilimumab, CP-675,206), ipilimumab (CTLA-4 antibody, also known as MDX-010, CAS No. 477202-00-9), vinblastine (also known as vinblastine sulfate, vincaleukoblastine and VLB sold under the tradenames Alkaban-AQ® and Velban®), vincristine (also known as vincristine sulfate, LCR, and VCR sold under the tradenames Oncovin® and Vincasar Pfs®), vinorelbine (sold under the tradename Navelbine®), Voninostat (sold under the tradename Zolinza® by Merck), Xaliproden (also known as SR57746, 1-[2-(2-naphthyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine, and described in U.S. Pat. No. 5,266,573), XL-518 (also known as GDC-0973, Cas No. 1029872-29-4, available from ACC Corp.); Selumetinib (5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide, also known as AZD6244 or ARRY 142886, described in PCT Publication No. WO2003077914); 2-[(2-chloro-4-iodophenyl)amino]-N-(cyclopropylmethoxy)-3,4-difluoro-benzamide (also known as CI-1040 or PD184352 and described in PCT Publication No. WO2000035436); N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-benzamide (also known as PD0325901 and described in PCT Publication No. WO2002006213); 2,3-bis[amino[(2-aminophenyl)thio]methylene]-butanedinitrile (also known as U0126 and described in U.S. Pat. No. 2,779,780); N-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl]-1-[(2R)-2,3-dihydroxypropyl]-cyclopropanesulfonamide (also known as RDEA119 or BAY869766 and described in PCT Publication No. WO2007014011); (3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione] (also known as E6201 and described in PCT Publication No. WO2003076424); 2′-Amino-3′-methoxyflavone (also known as PD98059 available from Biaffin GmbH & Co., KG, Germany); AS-703026 (CAS No. 1204531-26-9); AZD-8330 (also known as ARRY-424704 or ARRY-704, CAS No. 1204531-17-8); ARRY-438162 (CAS No. 1073666-70-2); GSK-1120212 (CAS No. 1204531-25-8); RO-4987665 (CAS No. 1204531-24-7); and TAK-733; Antiresorptive agents, Bisphosphonates, Bone anabolic agents, Calcitonin, Calcium, Calcium salts, Estrogen analogs, Raloxifene, RANKL inhibitors, Sodium fluoride, Strontium ranelate, Teriparatide, and Vitamin D.
• The dosages of the additional treatments and RNAi agents can be easily determined by one of ordinary skill in the art, and as described herein.
• Dosages and Effective Amounts of RNAi Agents
• The RNAi agents of the present disclosure are administered in a dosage of a therapeutically effective amount to a patient in need thereof.
• An “effective amount” or a “therapeutically effective amount” is an amount that treats a disease or medical condition of an individual, or, more generally, provides a nutritional, physiological or medical benefit to an individual. As used herein, the phrases “therapeutically effective amount” and “prophylactically effective amount” refer to an amount that provides a therapeutic benefit in the treatment, prevention, or management of pathological processes mediated by Beta-Catenin expression or an overt symptom of pathological processes mediated by Beta-Catenin expression. The specific amount that is therapeutically effective can be readily determined by an ordinary medical practitioner, and may vary depending on factors known in the art, such as, for example, the type of pathological processes mediated by Beta-Catenin expression, the patient's history and age, the stage of pathological processes mediated by Beta-Catenin expression, and the administration of other agents that inhibit pathological processes mediated by Beta-Catenin expression.
• In various embodiments of the present disclosure, the patient is at least about 1, 3, 6, or 9 months, or 1, 5, 10, 20, 30, 40, 50, 55, 60, 65, 70, or 75 years of age. In various embodiments of the present disclosure, the patient is no more than about 1, 3, 6, or 9 months, or 1, 5, 10, 20, 30, 40, 50, 55, 60, 65, 70, 75, 80, 90, or 100 years of age. In various embodiments the patient has a body weight of at least about 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380 or 400 lbs. In various embodiments of the present disclosure, the patient has a body weight of no more than about 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380 or 400 lbs.
• In various embodiments of the present disclosure, the dosage [measuring only the active ingredient(s)] can be at least about 1, 5, 10, 25, 50, 100, 200, 250, 300, 250, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 ng, 1, 5, 10, 25, 50, 100, 200, 250, 300, 250, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 micrograms, 1, 5, 10, 25, 50, 100, 200, 250, 300, 250, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 mg. In various embodiments of the present disclosure, the dosage can be no more than about 10, 25, 50, 100, 200, 250, 300, 250, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 mg. In various embodiments of the present disclosure, the dosage can be administered at least more than once a day, daily, more than once a weekly, weekly, bi-weekly, monthly, and/or every 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or a combination thereof.
• In various embodiments of the present disclosure, the dosage is correlated to the body weight or body surface area of the individual. The actual dosage level can be varied to obtain an amount of active agent which is effective for a particular patient, composition and mode of administration, without being toxic to the patient. The selected dose will depend on a variety of pharmacokinetic factors, including the activity of the particular RNAi agent employed, the route of administration, the rate of excretion of the RNAi agent, the duration of the treatment, other drugs, compounds and/or materials used in combination with the RNAi agent, the age, sex, weight, condition, general health and prior medical history of the patient, and like factors well known in the medical arts. A physician or veterinarian having ordinary skill in the art can readily determine the effective amount of the RNAi agent required. A suitable dose will be that amount which is the lowest dose effective to produce a therapeutic effect, or a dose low enough to produce a therapeutic effect without causing side effects.
• In addition to a therapeutically-effective dosage of one or more RNAi agents to Beta-Catenin, the pharmaceutical compositions of the present disclosure can comprise or be used in conjunction with an additional disease treatment which works synergistically with the RNAi agent. For example, the pharmaceutical composition can comprise an additional antagonist to Beta-Catenin.
• Additional Embodiments of RNAi Agents to Beta-Catenin
• In a particular embodiment, the present disclosure encompasses a composition comprising one or more Beta-Catenin RNAi agents. In one embodiment, the present disclosure comprises a RNAi agent comprising a sense strand and an anti-sense strand. In one embodiment, the anti-sense strand consists of, consists essentially of, or comprises the sequence of the anti-sense strand of, a RNAi agent listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the anti-sense strand consists of, consists essentially of, or comprises a sequence of at least 15 contiguous nt with 0, 1, 2, or 3 mismatches from that of, the anti-sense strand of any RNAi agent listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9. In one embodiment, the anti-sense strand consists of the sequence of the anti-sense strand of a RNAi agent listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and further comprises 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides. In one embodiment, the anti-sense strand consists of a sequence with 0, 1, 2, or 3 mismatches from that of the anti-sense strand of a RNAi agent listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and further comprises 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides.
• In various embodiments of the present disclosure, the composition of the claimed disclosure has the proviso that it does not comprise any particular individual RNAi agent listed in Tables 1, 2 or 3. In various embodiments of the present disclosure, the RNAi agent to Beta-Catenin has the proviso that it does not have the sequence of any Beta-Catenin RNAi agent disclosed in the patent or scientific literature, e.g., WO 2006/086772, US 2007 0207974, US 2007 0042381, US 2005 0255487, US 2007/0275914, US 2007 0039072, US 2006 0193870, or US 2008 0113351.
Additional Embodiments of RNAi Agents
• In another particular embodiment, the RNAi agent comprises any of the RNAi agents listed in Table 1, and modified and unmodified variants thereof.
• In another particular embodiment, the RNAi agent comprises the sense strand of any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In another particular embodiment, the RNAi agent comprises the anti-sense strand of any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In another particular embodiment, the RNAi agent comprises a sense strand with a sequence consisting of that of the sense strand of any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9 and modified and unmodified variants thereof.
• In another particular embodiment, the RNAi agent comprises an anti-sense strand with a sequence consisting of that of the anti-sense strand any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In another particular embodiment, the RNAi agent comprises a sense stand with a sequence consisting of that of the sense strand and/or an anti-sense strand with a sequence consisting of that of the anti-sense strand of any RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9.
• In another particular embodiment, the RNAi agent has a sequence consisting of that of any of the RNAi agents listed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• Embodiments Comprising One or More Efficacious RNAi Agents to Beta-Catenin
• In various embodiments of the present disclosure, the present disclosure comprises a RNAi agent demonstrating at least about 40, 50, 60, 70, 80, 90 or 95% knockdown (no more than about 60, 50, 40, 30, 20, 10, or 5% residual gene activity, respectively) of the Beta-Catenin gene at an in vitro concentration of 10 or 0.1 nM in HeLa cells.
• In various embodiments of the present disclosure, the composition comprises one or more RNAi agents capable of a Fold-Change at 10 nM at 24 hr of ≤0.05, ≤0.10, ≤0.20, ≤0.30, ≤0.40 (indicating a Beta-Catenin gene knock-down of at least 95, 90, 80, 70, or 60%, respectively, at a concentration of 10 nM at 24 hrs in HeLa cells). RNAi agents capable of these levels of activity are disclosed in the Tables herein.
• Embodiments Comprising One or More Efficacious RNAi Agents to Beta-Catenin
• In various embodiments of the present disclosure, the composition comprises one or more RNAi agents capable of a Fold-Change at 0.1 nM at 120 hr of ≤0.30, ≤0.20, or ≤0.10 (indicating a Beta-Catenin gene knock-down of at least 70, 80, or 90%, respectively, at a concentration of 0.1 nM at 120 hrs in HeLa cells). RNAi agents capable of these levels of activity are disclosed in the Tables herein.
• Various Embodiments Comprising One or More RNAi Agents to Beta-Catenin with Low EC50
• In various embodiments of the present disclosure, the composition comprises one or more RNAi agents capable of mediating 50% gene knockdown (EC50) of Beta-Catenin at a low concentration in HeLa cells. For many of the RNAi agents listed herein, an estimated EC50 was calculated. Cells were treated at 10 nM, 1 nM, 0.1 nM, 0.01 nM, and 0.001 nM of RNAi agent, and the data fit to a curve. The indicated EC50 is an estimated EC50 calculated from available data that is expected to give 50% gene knock-down of Beta-Catenin in HeLa cells. In various embodiments of the present disclosure, the composition comprises one or more RNAi agents capable of mediating 50% gene knockdown (EC50) at 100, 75, 50, 25, 10, 5, 2.5, 1, 0.75, 0.5, 0.25, 0.2, 0.12, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, or 0.02 nM or less in HeLa cells. RNAi agents capable of these levels of activity are disclosed in the Tables herein.
• Specific Embodiments of RNAi Agents to Beta-Catenin
• In one embodiment, the present disclosure pertains to: a composition comprising any one or more of: a RNAi agent comprising a sense strand and an anti-sense strand, wherein the anti-sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the anti-sense strand of: any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9 and modified or unmodified variants thereof.
• In one embodiment, the composition comprises any one or more of: a RNAi agent comprising a sense strand and an anti-sense strand, wherein the anti-sense strand comprises at least 15 contiguous nucleotides differing by 0 nucleotides from the anti-sense strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In one embodiment, the present disclosure pertains to a composition comprising any one or more of: any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In one embodiment, the present disclosure pertains to a composition comprising any one or more of: a RNAi agent comprising an anti-sense strand comprising the sequence of the anti-sense strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In one embodiment, the present disclosure pertains to a composition comprising any one or more of: a RNAi agent comprises an anti-sense strand consisting of the sequence of the anti-sense strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In one embodiment, the present disclosure pertains to a composition comprising any one or more of: a RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand is the second of the first strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In one embodiment, the present disclosure pertains to a composition comprising any one or more of: a RNAi agent comprising a first and a second strand, wherein the sequences of the first and the second strand are the sequences of the first and second strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• In one embodiment, the present disclosure pertains to a composition comprising any one or more of: a RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand is the second of the first strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof, wherein the first and/or second strand further comprise up to about 20 additional nucleotides.
• Additional Embodiments of Specific RNAi Agents to Beta-Catenin
• In one embodiment, the present disclosure comprises a RNAi agent comprising a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, or modified or unmodified variants thereof.
• Thus, in various embodiments, the present disclosure pertains to a composition comprising any one or more of the following:
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26104, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26063, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26082, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26034, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26091, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26047, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26651, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26696, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26109, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25941, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26028, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26652, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26742, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26921, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18893, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18983, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25950, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25951, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26042, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26043, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26673, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26704, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26068, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26183, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26700, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26701, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25942, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26076, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26031, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26210, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26664, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26691, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26740, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19765, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26158, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26180, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26078, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25894, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25964, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26156, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26670, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26743, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25890, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26044, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26685, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26731, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26800, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26066, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26682, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26684, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26757, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26788, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18963, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19076, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25943, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26052, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26665, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26746, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18974, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25938, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25944, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26178, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26669, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26730, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26825, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25956, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26822, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26108, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26752, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26779, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25891, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26101, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26181, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26218, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26660, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18966, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19074, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26179, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26722, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26768, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26920, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26020, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26713, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26727, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26808, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25958, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26105, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26674, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26781, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26801, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26813, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26816, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25945, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26203, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26021, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26040, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26069, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26134, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26702, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18933, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26690, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26698, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25910, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26747, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26810, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26083, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26061, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26904, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18903, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18980, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26202, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26679, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26719, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26758, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26783, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26902, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18892, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18897, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25902, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26705, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26782, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19082, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26176, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26196, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26199, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26678, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26683, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26729, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26804, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26900, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25914, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26060, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26763, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18902, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18914, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26100, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26128, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26193, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26765, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25960, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26018, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25893, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26823, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25940, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26190, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26675, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26797, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26916, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26755, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26901, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19004, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19009, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26148, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26186, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26737, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25955, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26029, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26131, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18894, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18939, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26654, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18929, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26135, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26774, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26780, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26819, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26918, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19050, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18994, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26769, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26666, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26784, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18969, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18986, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25929, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25932, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26095, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26908, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26071, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26912, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19054, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25918, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26903, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25931, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26146, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26200, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26917, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26794, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26910, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25939, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26032, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26776, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26806, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26748, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26725, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18958, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26672, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26905, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19056, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19762, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26919, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18946, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19066, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19746, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26057, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26073, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26689, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19008, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26026, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26761, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19752, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18981, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18927, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19753, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25907, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26671, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19080, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26075, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26681, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18976, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25900, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26126, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26688, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25912, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25930, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18995, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26802, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25892, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25947, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26088, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26098, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26778, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26215, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26739, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18950, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25949, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26141, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18961, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25957, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26826, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25963, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26019, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26035, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25946, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26714, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26022, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26096, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26132, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26062, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18991, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26164, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26209, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25895, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25933, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26017, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19749, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26653, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26759, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25924, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26153, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25953, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26764, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26790, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-20124, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25919, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18913, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26211, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18936, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25898, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26741, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19043, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26079, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19000, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25911, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26786, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19069, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26037, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26723, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19067, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25928, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26677, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19006, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19758, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26913, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25917, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26189, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26787, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26707, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26094, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26097, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26699, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26756, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26720, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25926, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26212, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26687, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26753, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18982, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18908, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18968, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25948, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26188, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26708, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25961, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26803, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19741, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26056, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25959, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26059, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26102, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26106, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26744, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26099, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26170, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19012, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26198, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26766, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18951, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18975, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26749, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18911, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26906, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-19747, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18960, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-25909, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26184, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26077, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26680, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26085, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18926, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18945, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26703, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26911, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26661, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-18905, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: AD-26142, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1245, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1249, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1250, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1450, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1545, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1755, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1814, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1816, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_1974, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_2202, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_2425, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_254, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_3146, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_3169, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_3196, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_3477, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_703, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_709, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_865, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_889, or modified or unmodified variants thereof.
• A RNAi agent comprising: a first strand and a second strand, wherein the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the first strand of: Set1_895, or modified or unmodified variants thereof.
• In various embodiments, the first and second strand can be either the sense and anti-sense strand, or the anti-sense and sense strand.
• Additional Embodiments of Specific RNAi Agents to Beta-Catenin
• In one embodiment, the present disclosure comprises a RNAi agent comprising an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of any RNAi in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, and modified and unmodified variants thereof.
• Thus, in various embodiments, the present disclosure pertains to a composition comprising any one or more of the following:
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26104, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26063, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26082, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26034, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26091, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26047, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26651, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26696, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26109, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25941, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26028, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26652, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26742, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26921, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18893, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18983, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25950, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25951, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26042, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26043, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26673, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26704, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26068, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26183, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26700, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26701, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25942, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26076, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26031, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26210, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26664, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26691, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26740, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19765, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26158, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26180, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26078, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25894, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25964, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26156, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26670, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26743, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25890, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26044, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26685, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26731, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26800, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26066, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26682, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26684, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26757, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26788, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18963, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19076, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25943, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26052, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26665, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26746, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18974, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25938, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25944, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26178, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26669, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26730, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26825, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25956, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26822, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26108, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26752, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26779, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25891, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26101, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26181, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26218, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26660, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18966, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19074, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26179, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26722, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26768, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26920, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26020, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26713, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26727, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26808, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25958, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26105, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26674, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26781, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26801, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26813, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26816, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25945, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26203, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26021, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26040, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26069, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26134, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26702, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18933, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26690, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26698, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25910, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26747, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26810, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26083, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26061, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26904, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18903, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18980, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26202, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26679, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26719, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26758, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26783, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26902, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18892, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18897, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25902, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26705, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26782, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19082, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26176, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26196, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26199, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26678, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26683, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26729, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26804, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26900, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25914, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26060, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26763, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18902, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18914, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26100, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26128, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26193, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26765, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25960, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26018, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25893, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26823, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25940, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26190, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26675, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26797, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26916, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26755, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26901, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19004, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19009, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26148, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26186, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26737, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25955, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26029, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26131, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18894, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18939, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26654, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18929, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26135, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26774, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26780, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26819, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26918, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19050, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18994, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26769, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26666, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26784, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18969, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18986, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25929, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25932, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26095, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26908, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26071, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26912, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19054, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25918, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26903, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25931, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26146, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26200, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26917, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26794, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26910, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25939, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26032, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26776, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26806, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26748, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26725, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18958, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26672, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26905, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19056, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19762, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26919, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18946, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19066, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19746, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26057, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26073, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26689, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19008, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26026, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26761, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19752, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18981, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18927, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19753, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25907, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26671, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19080, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26075, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26681, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18976, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25900, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26126, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26688, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25912, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25930, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18995, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26802, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25892, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25947, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26088, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26098, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26778, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26215, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26739, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18950, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25949, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26141, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18961, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25957, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26826, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25963, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26019, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26035, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25946, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26714, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26022, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26096, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26132, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26062, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18991, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26164, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26209, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25895, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25933, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26017, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19749, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26653, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26759, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25924, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26153, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25953, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26764, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26790, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-20124, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25919, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18913, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26211, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18936, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25898, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26741, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19043, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26079, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19000, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25911, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26786, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19069, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26037, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26723, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19067, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25928, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26677, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19006, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19758, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26913, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25917, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26189, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26787, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26707, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26094, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26097, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26699, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26756, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26720, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25926, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26212, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26687, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26753, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18982, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18908, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18968, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25948, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26188, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26708, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25961, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26803, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19741, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26056, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25959, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26059, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26102, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26106, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26744, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26099, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26170, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19012, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26198, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26766, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18951, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18975, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26749, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18911, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26906, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-19747, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18960, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-25909, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26184, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26077, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26680, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26085, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18926, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18945, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26703, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26911, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26661, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-18905, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of AD-26142, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1245, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1249, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1250, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1450, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1545, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1755, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1814, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1816, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_1974, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_2202, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_2425, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_254, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_3146, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_3169, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_3196, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_3477, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_703, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_709, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_865, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_889, or modified or unmodified variants thereof.
• A RNAi agent comprising: an anti-sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the anti-sense strand, and/or a sense strand comprising at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nt from the sequence of the sense strand, of Set1_895, or modified or unmodified variants thereof.
Additional Embodiments Encompassing Specific RNAi Agents to Beta-Catenin
• In various embodiments, the present disclosure pertains to a composition comprising one or more of the following:
• • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26104.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26063.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26082.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26034.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26091.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26047.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26651.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26696.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26109.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25941.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26028.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26652.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26742.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26921.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18893.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18983.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25950.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25951.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26042.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26043.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26673.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26704.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26068.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26183.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26700.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26701.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25942.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26076.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26031.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26210.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26664.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26691.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26740.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19765.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26158.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26180.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26078.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25894.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25964.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26156.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26670.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26743.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25890.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26044.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26685.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26731.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26800.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26066.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26682.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26684.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26757.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26788.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18963.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19076.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25943.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26052.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26665.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26746.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18974.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25938.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25944.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26178.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26669.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26730.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26825.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25956.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26822.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26108.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26752.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26779.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25891.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26101.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26181.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26218.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26660.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18966.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19074.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26179.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26722.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26768.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26920.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26020.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26713.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26727.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26808.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25958.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26105.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26674.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26781.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26801.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26813.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26816.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25945.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26203.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26021.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26040.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26069.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26134.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26702.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18933.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26690.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26698.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25910.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26747.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26810.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26083.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26061.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26904.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18903.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18980.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26202.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26679.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26719.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26758.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26783.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26902.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18892.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18897.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25902.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26705.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26782.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19082.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26176.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26196.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26199.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26678.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26683.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26729.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26804.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26900.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25914.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26060.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26763.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18902.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18914.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26100.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26128.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26193.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26765.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25960.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26018.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25893.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26823.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25940.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26190.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26675.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26797.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26916.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26755.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26901.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19004.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19009.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26148.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26186.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26737.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25955.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26029.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26131.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18894.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18939.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26654.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18929.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26135.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26774.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26780.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26819.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26918.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19050.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18994.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26769.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26666.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26784.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18969.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18986.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25929.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25932.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26095.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26908.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26071.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26912.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19054.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25918.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26903.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25931.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26146.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26200.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26917.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26794.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26910.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25939.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26032.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26776.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26806.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26748.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26725.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18958.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26672.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26905.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19056.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19762.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26919.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18946.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19066.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19746.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26057.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26073.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26689.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19008.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26026.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26761.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19752.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18981.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18927.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19753.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25907.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26671.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19080.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26075.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26681.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18976.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25900.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26126.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26688.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25912.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25930.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18995.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26802.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25892.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25947.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26088.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26098.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26778.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26215.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26739.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18950.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25949.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26141.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18961.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25957.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26826.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25963.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26019.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26035.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25946.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26714.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26022.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26096.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26132.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26062.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18991.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26164.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26209.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25895.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25933.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26017.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19749.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26653.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26759.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25924.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26153.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25953.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26764.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26790.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-20124.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25919.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18913.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26211.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18936.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25898.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26741.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19043.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26079.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19000.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25911.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26786.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19069.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26037.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26723.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19067.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25928.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26677.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19006.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19758.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26913.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25917.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26189.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26787.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26707.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26094.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26097.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26699.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26756.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26720.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25926.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26212.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26687.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26753.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18982.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18908.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18968.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25948.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26188.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26708.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25961.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26803.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19741.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26056.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25959.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26059.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26102.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26106.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26744.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26099.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26170.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19012.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26198.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26766.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18951.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18975.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26749.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18911.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26906.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-19747.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18960.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-25909.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26184.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26077.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26680.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26085.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18926.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18945.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26703.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26911.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26661.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-18905.
  • A RNAi agent comprising a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of AD-26142.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1245.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1249.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1250.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1450.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1545.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1755.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1814.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1816.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_1974.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_2202.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_2425.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_254.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_3146.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_3169.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_3196.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_3477.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_703.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_709.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_865.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_889.
  • A RNAi agent comprising: a sense strand and an anti-sense strand, wherein the sequence of the anti-sense strand is the sequence of the anti-sense strand of Set1_895.
Additional Embodiments Encompassing Specific RNAi Agents to Beta-Catenin
• In various embodiments, the present disclosure pertains to a composition comprising one or more of the following:
• • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26104, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26063, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26082, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26034, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26091, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26047, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26651, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26696, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26109, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25941, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26028, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26652, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26742, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26921, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18893, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18983, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25950, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25951, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26042, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26043, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26673, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26704, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26068, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26183, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26700, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26701, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25942, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26076, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26031, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26210, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26664, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26691, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26740, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19765, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26158, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26180, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26078, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25894, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25964, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26156, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26670, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26743, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25890, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26044, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26685, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26731, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26800, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26066, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26682, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26684, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26757, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26788, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18963, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19076, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25943, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26052, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26665, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26746, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18974, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25938, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25944, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26178, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26669, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26730, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26825, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25956, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26822, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26108, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26752, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26779, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25891, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26101, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26181, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26218, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26660, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18966, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19074, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26179, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26722, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26768, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26920, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26020, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26713, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26727, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26808, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25958, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26105, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26674, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26781, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26801, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26813, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26816, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25945, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26203, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26021, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26040, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26069, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26134, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26702, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18933, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26690, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26698, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25910, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26747, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26810, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26083, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26061, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26904, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18903, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18980, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26202, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26679, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26719, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26758, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26783, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26902, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18892, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18897, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25902, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26705, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26782, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19082, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26176, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26196, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26199, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26678, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26683, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26729, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26804, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26900, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25914, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26060, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26763, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18902, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18914, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26100, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26128, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26193, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26765, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25960, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26018, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25893, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26823, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25940, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26190, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26675, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26797, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26916, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26755, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26901, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19004, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19009, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26148, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26186, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26737, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25955, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26029, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26131, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18894, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18939, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26654, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18929, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26135, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26774, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26780, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26819, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26918, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19050, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18994, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26769, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26666, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26784, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18969, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18986, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25929, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25932, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26095, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26908, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26071, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26912, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19054, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25918, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26903, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25931, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26146, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26200, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26917, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26794, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26910, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25939, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26032, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26776, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26806, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26748, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26725, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18958, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26672, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26905, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19056, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19762, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26919, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18946, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19066, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19746, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26057, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26073, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26689, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19008, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26026, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26761, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19752, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18981, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18927, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19753, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25907, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26671, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19080, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26075, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26681, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18976, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25900, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26126, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26688, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25912, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25930, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18995, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26802, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25892, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25947, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26088, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26098, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26778, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26215, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26739, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18950, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25949, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26141, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18961, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25957, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26826, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25963, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26019, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26035, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25946, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26714, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26022, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26096, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26132, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26062, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18991, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26164, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26209, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25895, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25933, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26017, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19749, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26653, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26759, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25924, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26153, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25953, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26764, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26790, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-20124, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25919, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18913, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26211, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18936, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25898, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26741, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19043, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26079, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19000, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25911, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26786, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19069, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26037, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26723, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19067, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25928, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26677, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19006, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19758, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26913, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25917, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26189, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26787, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26707, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26094, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26097, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26699, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26756, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26720, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25926, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26212, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26687, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26753, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18982, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18908, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18968, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25948, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26188, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26708, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25961, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26803, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19741, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26056, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25959, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26059, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26102, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26106, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26744, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26099, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26170, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19012, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26198, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26766, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18951, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18975, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26749, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18911, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26906, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-19747, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18960, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-25909, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26184, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26077, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26680, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26085, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18926, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18945, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26703, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26911, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26661, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-18905, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of AD-26142, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1245, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1249, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1250, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1450, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1545, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1755, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1814, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1816, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_1974, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_2202, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_2425, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_254, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_3146, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_3169, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_3196, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_3477, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_703, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_709, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_865, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_889, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
  • A RNAi agent comprising: a first strand and a second strand, wherein the sequence of the first or second strand is the sequence of the first or second strand of Set1_895, and wherein the first and/or second strand further comprises up to about 20 additional nucleotides.
• Additional Embodiments of Specific RNAi Agents to Beta-Catenin.
• • In various embodiments, the present disclosure pertains to:
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6096 and/or 6117, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6097 and/or 6118, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6098 and/or 6119, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6100 and/or 6121, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6101 and/or 6122, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6103 and/or 6124, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6105 and/or 6126, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6106 and/or 6127, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, is or consists of the sequence of SEQ ID NOs: 6107 and/or 6128, or modified or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6096 and/or 6117, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6097 and/or 6118, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6098 and/or 6119, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6100 and/or 6121, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6101 and/or 6122, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6103 and/or 6124, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6105 and/or 6126, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6106 and/or 6127, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise the sequence of SEQ ID NOs: 6107 and/or 6128, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6096 and/or 6117, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6097 and/or 6118, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6098 and/or 6119, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6100 and/or 6121, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6101 and/or 6122, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6103 and/or 6124, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6105 and/or 6126, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6106 and/or 6127, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides of the sequence of SEQ ID NOs: 6107 and/or 6128, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6096 and/or 6117, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6097 and/or 6118, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6098 and/or 6119, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6100 and/or 6121, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6101 and/or 6122, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6103 and/or 6124, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6105 and/or 6126, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6106 and/or 6127, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
  • A RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand and/or the second strand, respectively, comprise at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NOs: 6107 and/or 6128, wherein the first and second strand are each no more than about 30 nucleotides in length, or unmodified variants thereof.
• In various embodiments, the first and second strand can be either the sense and anti-sense strand, or the anti-sense and sense strand.
• Additional Embodiments of Specific RNAi Agents to Beta-Catenin, Further Comprising Additional Nt.
• In various embodiments of the present disclosure, the RNAi agent comprises an anti-sense strand consisting of a sequence of at least 15 contiguous nucleotides with 0, 1, 2, or 3 mismatches from that of the anti-sense strand of any RNAi agent from Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9, or modified or unmodified variants thereof, wherein the anti-sense strand optionally further comprises 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more nt (or any range thereof, e.g., 0-1, 1-2,1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 2-3, 2-4, or 2-5 nt, etc.)
• Additional Embodiments Comprising Overlapping Groups of RNAi Agents to Beta-Catenin
• In various embodiments of the present disclosure, the present disclosure relates to groups of RNAi agents with overlapping sequences. Thus, the present disclosure encompasses groups of RNAi agents wherein each RNAi agent in the group overlaps with each other RNAi agent in the same group by at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or more nucleotides. In one embodiment, the overlap is at least 12 nt. Groups of sequences that overlap are shown in Table 4.
• Table 4 shows, for example, that AD-26022 and AD-26204 share the common technical feature of the sequence of CCUGUUCCCCUG (SEQ ID NO: 1319) in the sense strand, and the sequence of CAGGGGAACAGG (SEQ ID NO: 2714) in the anti-sense strand. Note of course that only a 12-nt portion of the overlap is shown; many groups of RNAi agents will overlap by more than 12 nt. The position within the gene is also indicated.
• The present disclosure thus encompasses various embodiments comprising groups of overlapping RNAi agents, for example (1) RNAi agents comprising the sequences of AD-26022 and AD-26204; (2) RNAi agents consisting of the sequences of AD-26022 and AD-26204; (3) RNAi agents comprising a sense strand and/or a anti-sense strand comprising a sequence of AD-26022 and AD-26204; (4) RNAi agents comprising a sense strand and/or a anti-sense strand comprising 15 contiguous nt with 0 to 3 mismatches from a sequence of AD-26022 and AD-26204; (5) RNAi agents comprising a sense strand comprising 15 contiguous nt with 0 to 3 mismatches from a sequence of AD-26022 and AD-26204; (6) RNAi agents comprising an anti-sense strand comprising 15 contiguous nt with 0 to 3 mismatches from a sequence of AD-26022 and AD-26204; etc. and similar embodiments reflecting all the overlapping groups of RNAi agents.
• Thus, in various embodiments, the RNAi agents of the present disclosure comprise a sense strand and an anti-sense (which may optionally be covalently linked, linked via a loop or linker, or contiguous), wherein the sense and/or anti-sense strand consist of, consist essentially of, or comprise sequences of at least 15 contiguous nt with 0, 1, 2, or 3 nt or bp mismatches of, the sense and/or anti-sense strand, respectively, of any one or more of the RNAi agents disclosed in Tables 1, 2, 3, 4, 5, 6, 7, 8 and/or 9 (or any member of a group of overlapping RNAi agents from Table 4), optionally further comprising 0-10 nt or bp.
Additional Definitions
• The articles “a” and “an” as used herein and in the claims refer to one or more than one (at least one) of the grammatical object of the article.
• The terms “RNAi agent,” “RNAi agents”, “RNAi agent(s)” and the like all refer without limitation to one or more RNAi agents of the present disclosure.
• The designations of particular example duplexes of RNAi agents to Beta-Catenin disclosed herein on occasion have the suffix “b” followed by a number. This indicates a batch number. Thus, the suffix “b1” indicates “batch 1.” Thus, a RNAi duplex designated, for example, “AD-18892-b1” is specifically from batch 1 and has the same sequence as any RNAi agent designated “AD-18892”.
• Unless defined otherwise, the technical and scientific terms used herein have the same meaning as that usually understood by a specialist familiar with the field to which the present disclosure belongs.
• Unless indicated otherwise, all methods, steps, techniques and manipulations that are not specifically described in detail can be performed and have been performed in a manner known per se, as will be clear to the skilled person. Reference is for example again made to the standard handbooks and the general background art mentioned herein and to the further references cited therein.
• Claims to the present disclosure are non-limiting and are provided below.
• Although particular embodiments and claims have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, or the scope of subject matter of claims of any corresponding future application. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the present disclosure without departing from the spirit and scope of the present disclosure as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. Redrafting of claim scope in later-filed corresponding applications may be due to limitations by the patent laws of various countries and should not be interpreted as giving up subject matter of the claims.
• Various additional formulations and obvious variants of the described RNAi agents to Beta-Catenin can be devised by those of ordinary skill in the art. Non-limiting example RNAi agents to Beta-Catenin are described in the Examples below, which do not limit the scope of the present disclosure as described in the claims.
Example 1
• Bioinformatics and Beta-Catenin RNAi Agent (siRNA) Sequences
• Bioinformatics
• Transcripts
• RNAi agent design is carried out to identify RNAi agents targeting the human Beta-Catenin gene (CTNNB1). The design uses the CTNNB1 transcript NM_001098210.1 from the NCBI (National Center for Biotechnology Information) Refseq collection. All RNAi agent duplexes are designed with 100% identity to all three human CTNNB1 transcripts (NM_001098210.1, NM_001098209.1, and NM_001904.3).
• siRNA Design and Specificity Prediction
• The predicted specificity of all possible 19-mers is predicted from each sequence. The CTNNB1 RNAi agents are used in a comprehensive search against the human transcriptome (defined as the set of NM_—and XM_—records within the human NCBI Refseq set) using the FASTA algorithm. The perl script ‘parseFasta.p1’ is then used to parse the alignments and generate a score based on the position and number of mismatches between the siRNA and any potential ‘off-target’ transcript. The off-target score is weighted to emphasize differences in the ‘seed’ region of siRNAs, in positions 2-9 from the 5′ end of the molecule. Each oligo-transcript pair from the FASTA search is given a mismatch score by summing the individual mismatch scores; mismatches in the position 2-9 are counted as 2.8, mismatches in the cleavage site positions 10-11 are counted as 1.2, and mismatches in region 12-19 counted as 1.0. An additional off-target prediction is carried out by comparing the frequency of heptamers and octomers derived from 3 distinct, seed-derived hexamers of each oligo. The hexamers from positions 2-7 relative to the 5′ start is used to create 2 heptamers and one octomer. The ‘heptamer1’ is created by adding a 3′ A to the hexamer; the heptamer2 is created by adding a 5′ A to the hexamer; the octomer is created by adding an A to both 5′ and 3′ ends of the hexamer. The frequency of octomers and heptamers in the human 3′UTRome (defined as the subsequence of the transcriptome from NCBI's Refseq database where the end of the coding region, the ‘CDS’, is clearly defined) is pre-calculated. The octomer frequency is normalized to the heptamer frequency using the median value from the range of octomer frequencies. A ‘mirSeedScore’ is then calculated by calculating the sum of ((3×normalized octomer count)+(2×heptamer2 count)+(1×heptamer1 count)).
• Both RNAi agent strands are assigned to a category of specificity according to the calculated scores: a score above 3 qualifies as highly specific, equal to 3 as specific and between 2.2 and 2.8 as moderately specific. RNAi agents are sorted by the specificity of the anti-sense strand. Oligonucleotides with perfect matches to known human microRNA seed regions are excluded.

• TABLE 2
  RNAi Agents to Beta-Catenin: Unmodified Sequences

  				Anti-
  		SENSE		sense
  		SEQ ID		SEQ ID
  DUPLEX	SENSE SEQUENCE	NO:	ANTI-SENSE SEQUENCE	NO:	POSITION

  AD-18892	UGGUGCUGACUAUCCAGUU	4771	AACUGGAUAGUCAGCACCA	5430	2500
  AD-18893	CCAUCUGUGCUCUUCGUCA	4772	UGACGAAGAGCACAGAUGG	5431	1659
  AD-18894	AUAAGCAGGUGGAUCUAUU	4773	AAUAGAUCCACCUGCUUAU	5432	3038
  AD-18895	AUCCAAAGAGUAGCUGCAG	4774	CUGCAGCUACUCUUUGGAU	5433	2096
  AD-18896	GACAAUGGCUACUCAAGCU	4775	AGCUUGAGUAGCCAUUGUC	5434	265
  AD-18897	CUGUUGGAUUGAUUCGAAA	4776	UUUCGAAUCAAUCCAACAG	5435	1797
  AD-18898	GCUGGCCUGGUUUGAUACU	4777	AGUAUCAAACCAGGCCAGC	5436	2587
  AD-18899	UCUAACCUCACUUGCAAUA	4778	UAUUGCAAGUGAGGUUAGA	5437	1541
  AD-18900	GAUAUCGCCAGGAUGAUCC	4779	GGAUCAUCCUGGCGAUAUC	5438	2391
  AD-18901	UGGCCAUCUUUAAGUCUGG	4780	CCAGACUUAAAGAUGGCCA	5439	954
  AD-18902	UGUAGAACACUAAUUCAUA	4781	UAUGAAUUAGUGUUCUACA	5440	2908
  AD-18903	AUCAGUAAGAGGUGUUAUU	4782	AAUAACACCUCUUACUGAU	5441	3104
  AD-18904	GUGCUCUUCGUCAUCUGAC	4783	GUCAGAUGACGAAGAGCAC	5442	1665
  AD-18905	UGGUUUGAUACUGACCUGU	4784	ACAGGUCAGUAUCAAACCA	5443	2594
  AD-18906	CCAGUUGCCUUUUAUCCCA	4785	UGGGAUAAAAGGCAACUGG	5444	3147
  AD-18907	CCUGGUUUGAUACUGACCU	4786	AGGUCAGUAUCAAACCAGG	5445	2592
  AD-18908	GACUAUCCAGUUGAUGGGC	4787	GCCCAUCAACUGGAUAGUC	5446	2507
  AD-18909	AGCCAAUGGCUUGGAAUGA	4788	UCAUUCCAAGCCAUUGGCU	5447	2325
  AD-18910	GCCAAUGGCUUGGAAUGAG	4789	CUCAUUCCAAGCCAUUGGC	5448	2326
  AD-18911	AGAUGAGGGCAUGCAGAUC	4790	GAUCUGCAUGCCCUCAUCU	5449	577
  AD-18912	GGUCCUCUGUGAACUUGCU	4791	AGCAAGUUCACAGAGGACC	5450	2116
  AD-18913	AACCCUAGCCUUGCUUGUU	4792	AACAAGCAAGGCUAGGGUU	5451	2708
  AD-18914	GAACACUAAUUCAUAAUCA	4793	UGAUUAUGAAUUAGUGUUC	5452	2912
  AD-18915	AUCAAACCCUAGCCUUGCU	4794	AGCAAGGCUAGGGUUUGAU	5453	2704
  AD-18916	ACCAGUUGCCUUUUAUCCC	4795	GGGAUAAAAGGCAACUGGU	5454	3146
  AD-18917	CUAACCUCACUUGCAAUAA	4796	UUAUUGCAAGUGAGGUUAG	5455	1542
  AD-18918	AUCCCACUAAUGUCCAGCG	4797	CGCUGGACAUUAGUGGGAU	5456	621
  AD-18919	CUGACUAUCCAGUUGAUGG	4798	CCAUCAACUGGAUAGUCAG	5457	2505
  AD-18920	GGCCUGGUUUGAUACUGAC	4799	GUCAGUAUCAAACCAGGCC	5458	2590
  AD-18921	GGUAAAUCAGUAAGAGGUG	4800	CACCUCUUACUGAUUUACC	5459	3099
  AD-18922	GCCUGGUUUGAUACUGACC	4801	GGUCAGUAUCAAACCAGGC	5460	2591
  AD-18923	CAGGGGUCCUCUGUGAACU	4802	AGUUCACAGAGGACCCCUG	5461	2112
  AD-18925	CUGGAAUCCAUUCUGGUGC	4803	GCACCAGAAUGGAUUCCAG	5462	366
  AD-18926	UGAGAUGGGUGGCCACCAC	4804	GUGGUGGCCACCCAUCUCA	5463	2479
  AD-18927	GAUGAUAUAAAUGUGGUCA	4805	UGACCACAUUUAUAUCAUC	5464	1502
  AD-18928	UGCUUUAUUCUCCCAUUGA	4806	UCAAUGGGAGAAUAAAGCA	5465	2073
  AD-18929	UUAUCAAACCCUAGCCUUG	4807	CAAGGCUAGGGUUUGAUAA	5466	2702
  AD-18930	CCACUGGCCUCUGAUAAAG	4808	CUUUAUCAGAGGCCAGUGG	5467	1774
  AD-18931	AACUUGCCACACGUGCAAU	4809	AUUGCACGUGUGGCAAGUU	5468	708
  AD-18932	GCUCUUCGUCAUCUGACCA	4810	UGGUCAGAUGACGAAGAGC	5469	1667
  AD-18933	GUAACAAUACAAAUGGAUU	4811	AAUCCAUUUGUAUUGUUAC	5470	2629
  AD-18934	GGGGUCCUCUGUGAACUUG	4812	CAAGUUCACAGAGGACCCC	5471	2114
  AD-18935	CAAACCCUAGCCUUGCUUG	4813	CAAGCAAGGCUAGGGUUUG	5472	2706
  AD-18936	GAGUAAUGGUGUAGAACAC	4814	GUGUUCUACACCAUUACUC	5473	2899
  AD-18937	GGAAGACAUCACUGAGCCU	4815	AGGCUCAGUGAUGUCUUCC	5474	1639
  AD-18938	GGGAAGACAUCACUGAGCC	4816	GGCUCAGUGAUGUCUUCCC	5475	1638
  AD-18939	GGUGUAGAACACUAAUUCA	4817	UGAAUUAGUGUUCUACACC	5476	2906
  AD-18940	UACCAGUUGCCUUUUAUCC	4818	GGAUAAAAGGCAACUGGUA	5477	3145
  AD-18941	GGAUAUCGCCAGGAUGAUC	4819	GAUCAUCCUGGCGAUAUCC	5478	2390
  AD-18942	AAACCCUAGCCUUGCUUGU	4820	ACAAGCAAGGCUAGGGUUU	5479	2707
  AD-18943	CUCUUCGUCAUCUGACCAG	4821	CUGGUCAGAUGACGAAGAG	5480	1668
  AD-18944	UGACUAUCCAGUUGAUGGG	4822	CCCAUCAACUGGAUAGUCA	5481	2506
  AD-18945	ACAAGCAGAGUGCUGAAGG	4823	CCUUCAGCACUCUGCUUGU	5482	1286
  AD-18946	CAUCUGUGCUCUUCGUCAU	4824	AUGACGAAGAGCACAGAUG	5483	1660
  AD-18947	CAAUGGCUUGGAAUGAGAC	4825	GUCUCAUUCCAAGCCAUUG	5484	2328
  AD-18948	ACUGGCCUCUGAUAAAGGC	4826	GCCUUUAUCAGAGGCCAGU	5485	1776
  AD-18949	UCAUCCCACUAAUGUCCAG	4827	CUGGACAUUAGUGGGAUGA	5486	619
  AD-18950	AAAAGGAAGCUUCCAGACA	4828	UGUCUGGAAGCUUCCUUUU	5487	807
  AD-18951	CGUUCUUUUCACUCUGGUG	4829	CACCAGAGUGAAAAGAACG	5488	2417
  AD-18952	AAAGUUGUUGUAACCUGCU	4830	AGCAGGUUACAACAACUUU	5489	3165
  AD-18953	ACAAUGGCUACUCAAGCUG	4831	CAGCUUGAGUAGCCAUUGU	5490	266
  AD-18954	CUCAUCCCACUAAUGUCCA	4832	UGGACAUUAGUGGGAUGAG	5491	618
  AD-18955	AGGGGUCCUCUGUGAACUU	4833	AAGUUCACAGAGGACCCCU	5492	2113
  AD-18956	AAGCAGGUGGAUCUAUUUC	4834	GAAAUAGAUCCACCUGCUU	5493	3040
  AD-18957	AAGUUGUUGUAACCUGCUG	4835	CAGCAGGUUACAACAACUU	5494	3166
  AD-18958	AGCAGGUGGAUCUAUUUCA	4836	UGAAAUAGAUCCACCUGCU	5495	3041
  AD-18959	AGGGCAUGCAGAUCCCAUC	4837	GAUGGGAUCUGCAUGCCCU	5496	582
  AD-18960	AAAUGGUUCAGAAUUAAAC	4838	GUUUAAUUCUGAACCAUUU	5497	3220
  AD-18961	UGAACUUGCUCAGGACAAG	4839	CUUGUCCUGAGCAAGUUCA	5498	2125
  AD-18962	AAGAGUAGCUGCAGGGGUC	4840	GACCCCUGCAGCUACUCUU	5499	2101
  AD-18963	CCCACUGGCCUCUGAUAAA	4841	UUUAUCAGAGGCCAGUGGG	5500	1773
  AD-18964	CUGGCCUGGUUUGAUACUG	4842	CAGUAUCAAACCAGGCCAG	5501	2588
  AD-18965	UUGAUACUGACCUGUAAAU	4843	AUUUACAGGUCAGUAUCAA	5502	2598
  AD-18966	GUGUAGAACACUAAUUCAU	4844	AUGAAUUAGUGUUCUACAC	5503	2907
  AD-18967	ACUAUCCAGUUGAUGGGCU	4845	AGCCCAUCAACUGGAUAGU	5504	2508
  AD-18968	AAAUCAGUAAGAGGUGUUA	4846	UAACACCUCUUACUGAUUU	5505	3102
  AD-18969	GCAGGUGGAUCUAUUUCAU	4847	AUGAAAUAGAUCCACCUGC	5506	3042
  AD-18970	CUGGUGCUGACUAUCCAGU	4848	ACUGGAUAGUCAGCACCAG	5507	2499
  AD-18971	GUGAACUUGCUCAGGACAA	4849	UUGUCCUGAGCAAGUUCAC	5508	2124
  AD-18972	UCAGUAAGAGGUGUUAUUU	4850	AAAUAACACCUCUUACUGA	5509	3105
  AD-18973	CCUCUGUGAACUUGCUCAG	4851	CUGAGCAAGUUCACAGAGG	5510	2119
  AD-18974	UUGGCUGAACCAUCACAGA	4852	UCUGUGAUGGUUCAGCCAA	5511	641
  AD-18975	UCAGCUGGCCUGGUUUGAU	4853	AUCAAACCAGGCCAGCUGA	5512	2584
  AD-18976	GUAGCUGCAGGGGUCCUCU	4854	AGAGGACCCCUGCAGCUAC	5513	2105
  AD-18977	AGGAGCUAAAAUGGCAGUG	4855	CACUGCCAUUUUAGCUCCU	5514	1069
  AD-18978	AUGGCUUGGAAUGAGACUG	4856	CAGUCUCAUUCCAAGCCAU	5515	2330
  AD-18979	UUGGAUAUCGCCAGGAUGA	4857	UCAUCCUGGCGAUAUCCAA	5516	2388
  AD-18980	GGUUCAGAAUUAAACUUUU	4858	AAAAGUUUAAUUCUGAACC	5517	3224
  AD-18981	GGGUAAAUCAGUAAGAGGU	4859	ACCUCUUACUGAUUUACCC	5518	3098
  AD-18982	AUACCAUUCCAUUGUUUGU	4860	ACAAACAAUGGAAUGGUAU	5519	2049
  AD-18983	ACUGUUGGAUUGAUUCGAA	4861	UUCGAAUCAAUCCAACAGU	5520	1796
  AD-18984	AACUUGCUCAGGACAAGGA	4862	UCCUUGUCCUGAGCAAGUU	5521	2127
  AD-18985	AUGCUUAAAAUAAGCAGGU	4863	ACCUGCUUAUUUUAAGCAU	5522	3029
  AD-18986	GUUUGAUACUGACCUGUAA	4864	UUACAGGUCAGUAUCAAAC	5523	2596
  AD-18987	AAUGGUUCAGAAUUAAACU	4865	AGUUUAAUUCUGAACCAUU	5524	3221
  AD-18988	UAUCCCAAAGUUGUUGUAA	4866	UUACAACAACUUUGGGAUA	5525	3159
  AD-18989	AUCAGCUGGCCUGGUUUGA	4867	UCAAACCAGGCCAGCUGAU	5526	2583
  AD-18990	CCUGCCAUCUGUGCUCUUC	4868	GAAGAGCACAGAUGGCAGG	5527	1655
  AD-18991	GCAGAAUACAAAUGAUGUA	4869	UACAUCAUUUGUAUUCUGC	5528	874
  AD-18992	UAUGCUUAAAAUAAGCAGG	4870	CCUGCUUAUUUUAAGCAUA	5529	3028
  AD-18993	AAUAAGCAGGUGGAUCUAU	4871	AUAGAUCCACCUGCUUAUU	5530	3037
  AD-18994	UGAUAUAAAUGUGGUCACC	4872	GGUGACCACAUUUAUAUCA	5531	1504
  AD-18995	GUAGGGUAAAUCAGUAAGA	4873	UCUUACUGAUUUACCCUAC	5532	3095
  AD-18996	UAUCAAACCCUAGCCUUGC	4874	GCAAGGCUAGGGUUUGAUA	5533	2703
  AD-18997	CCUUUUAUCCCAAAGUUGU	4875	ACAACUUUGGGAUAAAAGG	5534	3154
  AD-18998	GGUAGGGUAAAUCAGUAAG	4876	CUUACUGAUUUACCCUACC	5535	3094
  AD-18999	UGAUACUGACCUGUAAAUC	4877	GAUUUACAGGUCAGUAUCA	5536	2599
  AD-19000	GGCUGAACCAUCACAGAUG	4878	CAUCUGUGAUGGUUCAGCC	5537	643
  AD-19001	UGGAUAUCGCCAGGAUGAU	4879	AUCAUCCUGGCGAUAUCCA	5538	2389
  AD-19002	UCUUCGUCAUCUGACCAGC	4880	GCUGGUCAGAUGACGAAGA	5539	1669
  AD-19003	UAGCUGCAGGGGUCCUCUG	4881	CAGAGGACCCCUGCAGCUA	5540	2106
  AD-19004	UGUUGUAACCUGCUGUGAU	4882	AUCACAGCAGGUUACAACA	5541	3170
  AD-19005	AAUCAGUAAGAGGUGUUAU	4883	AUAACACCUCUUACUGAUU	5542	3103
  AD-19006	UGGCUGAACCAUCACAGAU	4884	AUCUGUGAUGGUUCAGCCA	5543	642
  AD-19007	GAAUUAAACUUUUAAUUCA	4885	UGAAUUAAAAGUUUAAUUC	5544	3230
  AD-19008	AUGGUUCAGAAUUAAACUU	4886	AAGUUUAAUUCUGAACCAU	5545	3222
  AD-19009	UGGUGUAGAACACUAAUUC	4887	GAAUUAGUGUUCUACACCA	5546	2905
  AD-19010	AUGGUGUAGAACACUAAUU	4888	AAUUAGUGUUCUACACCAU	5547	2904
  AD-19011	AUGAGGGCAUGCAGAUCCC	4889	GGGAUCUGCAUGCCCUCAU	5548	579
  AD-19012	GUUGUAACCUGCUGUGAUA	4890	UAUCACAGCAGGUUACAAC	5549	3171
  AD-19042	GCUGACUAUCCAGUUGAUG	4891	CAUCAACUGGAUAGUCAGC	5550	2504
  AD-19043	UAAGCAGGUGGAUCUAUUU	4892	AAAUAGAUCCACCUGCUUA	5551	3039
  AD-19044	UAAAAUAAGCAGGUGGAUC	4893	GAUCCACCUGCUUAUUUUA	5552	3034
  AD-19045	GAUAUAAAUGUGGUCACCU	4894	AGGUGACCACAUUUAUAUC	5553	1505
  AD-19046	AAGCAGAGUGCUGAAGGUG	4895	CACCUUCAGCACUCUGCUU	5554	1288
  AD-19047	UGUGAACUUGCUCAGGACA	4896	UGUCCUGAGCAAGUUCACA	5555	2123
  AD-19048	CAUCCCACUAAUGUCCAGC	4897	GCUGGACAUUAGUGGGAUG	5556	620
  AD-19049	CAAAGUUGUUGUAACCUGC	4898	GCAGGUUACAACAACUUUG	5557	3164
  AD-19050	UAAAUCAGUAAGAGGUGUU	4899	AACACCUCUUACUGAUUUA	5558	3101
  AD-19051	AAUGGCUUGGAAUGAGACU	4900	AGUCUCAUUCCAAGCCAUU	5559	2329
  AD-19052	GGGUCCUCUGUGAACUUGC	4901	GCAAGUUCACAGAGGACCC	5560	2115
  AD-19053	GAGUAACAAUACAAAUGGA	4902	UCCAUUUGUAUUGUUACUC	5561	2627
  AD-19054	UAAUGGUGUAGAACACUAA	4903	UUAGUGUUCUACACCAUUA	5562	2902
  AD-19055	GUGGACAAUGGCUACUCAA	4904	UUGAGUAGCCAUUGUCCAC	5563	262
  AD-19056	AACUGUCUUUGGACUCUCA	4905	UGAGAGUCCAAAGACAGUU	5564	1406
  AD-19057	CCCUGGUGCUGACUAUCCA	4906	UGGAUAGUCAGCACCAGGG	5565	2497
  AD-19058	CAGGUGGAUCUAUUUCAUG	4907	CAUGAAAUAGAUCCACCUG	5566	3043
  AD-19059	UGGCCUGGUUUGAUACUGA	4908	UCAGUAUCAAACCAGGCCA	5567	2589
  AD-19060	AGCUGGCCUGGUUUGAUAC	4909	GUAUCAAACCAGGCCAGCU	5568	2586
  AD-19061	GCCAUCUGUGCUCUUCGUC	4910	GACGAAGAGCACAGAUGGC	5569	1658
  AD-19062	UACCAUUCCAUUGUUUGUG	4911	CACAAACAAUGGAAUGGUA	5570	2050
  AD-19063	CCCUUGGAUAUCGCCAGGA	4912	UCCUGGCGAUAUCCAAGGG	5571	2385
  AD-19064	AGGGAAGACAUCACUGAGC	4913	GCUCAGUGAUGUCUUCCCU	5572	1637
  AD-19065	GAACUUGCCACACGUGCAA	4914	UUGCACGUGUGGCAAGUUC	5573	707
  AD-19066	UUUGAUACUGACCUGUAAA	4915	UUUACAGGUCAGUAUCAAA	5574	2597
  AD-19067	UCCCAAAGUUGUUGUAACC	4916	GGUUACAACAACUUUGGGA	5575	3161
  AD-19068	CAGAAUACAAAUGAUGUAG	4917	CUACAUCAUUUGUAUUCUG	5576	875
  AD-19069	AGGUGGAUCUAUUUCAUGU	4918	ACAUGAAAUAGAUCCACCU	5577	3044
  AD-19070	GCUCAUCCCACUAAUGUCC	4919	GGACAUUAGUGGGAUGAGC	5578	617
  AD-19071	CCUGGUGCUGACUAUCCAG	4920	CUGGAUAGUCAGCACCAGG	5579	2498
  AD-19072	UGGAAUCCAUUCUGGUGCC	4921	GGCACCAGAAUGGAUUCCA	5580	367
  AD-19073	CCAGGACCUCAUGGAUGGG	4922	CCCAUCCAUGAGGUCCUGG	5581	2545
  AD-19074	AACCUCACUUGCAAUAAUU	4923	AAUUAUUGCAAGUGAGGUU	5582	1544
  AD-19075	CAGUUGCCUUUUAUCCCAA	4924	UUGGGAUAAAAGGCAACUG	5583	3148
  AD-19076	GUAGAACACUAAUUCAUAA	4925	UUAUGAAUUAGUGUUCUAC	5584	2909
  AD-19077	CUAUCCAGUUGAUGGGCUG	4926	CAGCCCAUCAACUGGAUAG	5585	2509
  AD-19078	CACUGGCCUCUGAUAAAGG	4927	CCUUUAUCAGAGGCCAGUG	5586	1775
  AD-19079	ACUGUCUUUGGACUCUCAG	4928	CUGAGAGUCCAAAGACAGU	5587	1407
  AD-19080	CCAAUGGCUUGGAAUGAGA	4929	UCUCAUUCCAAGCCAUUGG	5588	2327
  AD-19081	GCUUAAAAUAAGCAGGUGG	4930	CCACCUGCUUAUUUUAAGC	5589	3031
  AD-19082	AUCUGUGCUCUUCGUCAUC	4931	GAUGACGAAGAGCACAGAU	5590	1661
  AD-19083	CCCAAAGUUGUUGUAACCU	4932	AGGUUACAACAACUUUGGG	5591	3162
  AD-19738	UACCCAGCGCCGUACGUCC	4933	GGACGUACGGCGCUGGGUA	5592	1906
  AD-19739	ACGCUAUCAUGCGUUCUCC	4934	GGAGAACGCAUGAUAGCGU	5593	825
  AD-19740	CAUGCACCUUUGCGUGAGC	4935	GCUCACGCAAAGGUGCAUG	5594	1838
  AD-19741	GAAUGCAGUUCGCCUUCAC	4936	GUGAAGGCGAACUGCAUUC	5595	1714
  AD-19742	GGUGCCAUUCCACGACUAG	4937	CUAGUCGUGGAAUGGCACC	5596	1859
  AD-19743	AAGCGGCUGUUAGUCACUG	4938	CAGUGACUAACAGCCGCUU	5597	324
  AD-19744	UCGAGCUCAGAGGGUACGA	4939	UCGUACCCUCUGAGCUCGA	5598	535
  AD-19745	GACACGCUAUCAUGCGUUC	4940	GAACGCAUGAUAGCGUGUC	5599	822
  AD-19746	CGCUAUCAUGCGUUCUCCU	4941	AGGAGAACGCAUGAUAGCG	5600	826
  AD-19747	GUGUCUGCUAUUGUACGUA	4942	UACGUACAAUAGCAGACAC	5601	851
  AD-19748	GUCUGCUCUAGUAAUAAGC	4943	GCUUAUUACUAGAGCAGAC	5602	1313
  AD-19749	GUGCCAUUCCACGACUAGU	4944	ACUAGUCGUGGAAUGGCAC	5603	1860
  AD-19750	AUGUUCACAACCGAAUUGU	4945	ACAAUUCGGUUGUGAACAU	5604	2016
  AD-19751	CCACGACUAGUUCAGUUGC	4946	GCAACUGAACUAGUCGUGG	5605	1868
  AD-19752	CACGACUAGUUCAGUUGCU	4947	AGCAACUGAACUAGUCGUG	5606	1869
  AD-19753	AGUUCAGUUGCUUGUUCGU	4948	ACGAACAAGCAACUGAACU	5607	1876
  AD-19754	CCCAGCGCCGUACGUCCAU	4949	AUGGACGUACGGCGCUGGG	5608	1908
  AD-19755	GAGUUACUUCACUCUAGGA	4950	UCCUAGAGUGAAGUAACUC	5609	2192
  AD-19756	ACAGUAUGCAAUGACUCGA	4951	UCGAGUCAUUGCAUACUGU	5610	520
  AD-19757	UAUGCAAUGACUCGAGCUC	4952	GAGCUCGAGUCAUUGCAUA	5611	524
  AD-19758	CCCACUAAUGUCCAGCGUU	4953	AACGCUGGACAUUAGUGGG	5612	623
  AD-19759	GACCUUGCAUAACCUUUCC	4954	GGAAAGGUUAUGCAAGGUC	5613	916
  AD-19760	UAUUACGACAGACUGCCUU	4955	AAGGCAGUCUGUCGUAAUA	5614	1153
  AD-19761	AUCUGACCAGCCGACACCA	4956	UGGUGUCGGCUGGUCAGAU	5615	1677
  AD-19762	CAUUCCACGACUAGUUCAG	4957	CUGAACUAGUCGUGGAAUG	5616	1864
  AD-19763	GUUUUGAAAAUCCAGCGUG	4958	CACGCUGGAUUUUCAAAAC	5617	246
  AD-19765	GCGUUUGGCUGAACCAUCA	4959	UGAUGGUUCAGCCAAACGC	5618	637
  AD-19766	ACACGCUAUCAUGCGUUCU	4960	AGAACGCAUGAUAGCGUGU	5619	823
  AD-19767	UAUGCCAUUACAACUCUCC	4961	GGAGAGUUGUAAUGGCAUA	5620	1028
  AD-19768	UCUGCUCUAGUAAUAAGCC	4962	GGCUUAUUACUAGAGCAGA	5621	1314
  AD-20124	CGGGAUGUUCACAACCGAA	4963	UUCGGUUGUGAACAUCCCG	5622	2012
  AD-25889	ACAAUACAAAUGGAUUUUG	4964	CAAAAUCCAUUUGUAUUGU	5623	2632
  AD-25890	ACAAAUGGAUUUUGGGAGU	4965	ACUCCCAAAAUCCAUUUGU	5624	2637
  AD-25891	UUGGGAGUGACUCAAGAAG	4966	CUUCUUGAGUCACUCCCAA	5625	2648
  AD-25892	UGGGAGUGACUCAAGAAGU	4967	ACUUCUUGAGUCACUCCCA	5626	2649
  AD-25893	GAAGUGAAGAAUGCACAAG	4968	CUUGUGCAUUCUUCACUUC	5627	2663
  AD-25894	AAGUGAAGAAUGCACAAGA	4969	UCUUGUGCAUUCUUCACUU	5628	2664
  AD-25895	GAUGGAAUUUAUCAAACCC	4970	GGGUUUGAUAAAUUCCAUC	5629	2694
  AD-25896	AUGGAAUUUAUCAAACCCU	4971	AGGGUUUGAUAAAUUCCAU	5630	2695
  AD-25897	GGAAUUUAUCAAACCCUAG	4972	CUAGGGUUUGAUAAAUUCC	5631	2697
  AD-25898	GAAUUUAUCAAACCCUAGC	4973	GCUAGGGUUUGAUAAAUUC	5632	2698
  AD-25899	AAUUUAUCAAACCCUAGCC	4974	GGCUAGGGUUUGAUAAAUU	5633	2699
  AD-25900	GAAUAUCUGUAAUGGUACU	4975	AGUACCAUUACAGAUAUUC	5634	2751
  AD-25901	AAUAUCUGUAAUGGUACUG	4976	CAGUACCAUUACAGAUAUU	5635	2752
  AD-25902	AUAUCUGUAAUGGUACUGA	4977	UCAGUACCAUUACAGAUAU	5636	2753
  AD-25903	UUUUAAGUCUCUCGUAGUG	4978	CACUACGAGAGACUUAAAA	5637	2832
  AD-25904	UUUAAGUCUCUCGUAGUGU	4979	ACACUACGAGAGACUUAAA	5638	2833
  AD-25905	AGUCUCUCGUAGUGUUAAG	4980	CUUAACACUACGAGAGACU	5639	2837
  AD-25906	UCGUAGUGUUAAGUUAUAG	4981	CUAUAACUUAACACUACGA	5640	2843
  AD-25907	CGUAGUGUUAAGUUAUAGU	4982	ACUAUAACUUAACACUACG	5641	2844
  AD-25908	GUAGUGUUAAGUUAUAGUG	4983	CACUAUAACUUAACACUAC	5642	2845
  AD-25909	UAGUGUUAAGUUAUAGUGA	4984	UCACUAUAACUUAACACUA	5643	2846
  AD-25910	UAGUGAAUACUGCUACAGC	4985	GCUGUAGCAGUAUUCACUA	5644	2859
  AD-25911	AACACUAAUUCAUAAUCAC	4986	GUGAUUAUGAAUUAGUGUU	5645	2913
  AD-25912	ACACUAAUUCAUAAUCACU	4987	AGUGAUUAUGAAUUAGUGU	5646	2914
  AD-25913	UAAUUGUAAUCUGAAUAAA	4988	UUUAUUCAGAUUACAAUUA	5647	2938
  AD-25914	AUUGUAAUCUGAAUAAAGU	4989	ACUUUAUUCAGAUUACAAU	5648	2940
  AD-25915	UUGUAAUCUGAAUAAAGUG	4990	CACUUUAUUCAGAUUACAA	5649	2941
  AD-25916	UGUAAUCUGAAUAAAGUGU	4991	ACACUUUAUUCAGAUUACA	5650	2942
  AD-25917	GACAAAUAGAAAAUGGUCC	4992	GGACCAUUUUCUAUUUGUC	5651	2991
  AD-25918	ACAAAUAGAAAAUGGUCCA	4993	UGGACCAUUUUCUAUUUGU	5652	2992
  AD-25919	UAGAAAAUGGUCCAAUUAG	4994	CUAAUUGGACCAUUUUCUA	5653	2997
  AD-25920	AGAAAAUGGUCCAAUUAGU	4995	ACUAAUUGGACCAUUUUCU	5654	2998
  AD-25921	UAUUUGGGAUAUGUAUGGG	4996	CCCAUACAUAUCCCAAAUA	5655	3077
  AD-25922	AUUUGGGAUAUGUAUGGGU	4997	ACCCAUACAUAUCCCAAAU	5656	3078
  AD-25923	UUGGGAUAUGUAUGGGUAG	4998	CUACCCAUACAUAUCCCAA	5657	3080
  AD-25924	GGAUAUGUAUGGGUAGGGU	4999	ACCCUACCCAUACAUAUCC	5658	3083
  AD-25925	AAGAGGUGUUAUUUGGAAC	5000	GUUCCAAAUAACACCUCUU	5659	3110
  AD-25926	AGAGGUGUUAUUUGGAACC	5001	GGUUCCAAAUAACACCUCU	5660	3111
  AD-25927	GAGGUGUUAUUUGGAACCU	5002	AGGUUCCAAAUAACACCUC	5661	3112
  AD-25928	UGGAACCUUGUUUUGGACA	5003	UGUCCAAAACAAGGUUCCA	5662	3123
  AD-25929	GGAACCUUGUUUUGGACAG	5004	CUGUCCAAAACAAGGUUCC	5663	3124
  AD-25930	GAACCUUGUUUUGGACAGU	5005	ACUGUCCAAAACAAGGUUC	5664	3125
  AD-25931	GUUUUGGACAGUUUACCAG	5006	CUGGUAAACUGUCCAAAAC	5665	3132
  AD-25932	UUUUGGACAGUUUACCAGU	5007	ACUGGUAAACUGUCCAAAA	5666	3133
  AD-25933	UUGGACAGUUUACCAGUUG	5008	CAACUGGUAAACUGUCCAA	5667	3135
  AD-25934	GUUGUUGUAACCUGCUGUG	5009	CACAGCAGGUUACAACAAC	5668	3168
  AD-25935	UUGUUGUAACCUGCUGUGA	5010	UCACAGCAGGUUACAACAA	5669	3169
  AD-25936	UUGUAACCUGCUGUGAUAC	5011	GUAUCACAGCAGGUUACAA	5670	3172
  AD-25937	AUGCUUCAAGAGAAAAUGC	5012	GCAUUUUCUCUUGAAGCAU	5671	3192
  AD-25938	AGUGAAGAAUGCACAAGAA	5013	UUCUUGUGCAUUCUUCACU	5672	2665
  AD-25939	AAUGGAUCACAAGAUGGAA	5014	UUCCAUCUUGUGAUCCAUU	5673	2682
  AD-25940	AUGGAUCACAAGAUGGAAU	5015	AUUCCAUCUUGUGAUCCAU	5674	2683
  AD-25941	UGGAUCACAAGAUGGAAUU	5016	AAUUCCAUCUUGUGAUCCA	5675	2684
  AD-25942	GGAUCACAAGAUGGAAUUU	5017	AAAUUCCAUCUUGUGAUCC	5676	2685
  AD-25943	GAUCACAAGAUGGAAUUUA	5018	UAAAUUCCAUCUUGUGAUC	5677	2686
  AD-25944	AUCACAAGAUGGAAUUUAU	5019	AUAAAUUCCAUCUUGUGAU	5678	2687
  AD-25945	UGGAAUUUAUCAAACCCUA	5020	UAGGGUUUGAUAAAUUCCA	5679	2696
  AD-25946	ACCCUAGCCUUGCUUGUUA	5021	UAACAAGCAAGGCUAGGGU	5680	2709
  AD-25947	CCCUAGCCUUGCUUGUUAA	5022	UUAACAAGCAAGGCUAGGG	5681	2710
  AD-25948	CCUAGCCUUGCUUGUUAAA	5023	UUUAACAAGCAAGGCUAGG	5682	2711
  AD-25949	CUAGCCUUGCUUGUUAAAU	5024	AUUUAACAAGCAAGGCUAG	5683	2712
  AD-25950	UAGCCUUGCUUGUUAAAUU	5025	AAUUUAACAAGCAAGGCUA	5684	2713
  AD-25951	AGCCUUGCUUGUUAAAUUU	5026	AAAUUUAACAAGCAAGGCU	5685	2714
  AD-25952	UUAAGUCUCUCGUAGUGUU	5027	AACACUACGAGAGACUUAA	5686	2834
  AD-25953	UAAGUCUCUCGUAGUGUUA	5028	UAACACUACGAGAGACUUA	5687	2835
  AD-25954	AAGUCUCUCGUAGUGUUAA	5029	UUAACACUACGAGAGACUU	5688	2836
  AD-25955	CUCGUAGUGUUAAGUUAUA	5030	UAUAACUUAACACUACGAG	5689	2842
  AD-25956	AGUGUUAAGUUAUAGUGAA	5031	UUCACUAUAACUUAACACU	5690	2847
  AD-25957	GUGUUAAGUUAUAGUGAAU	5032	AUUCACUAUAACUUAACAC	5691	2848
  AD-25958	CUACAGCAAUUUCUAAUUU	5033	AAAUUAGAAAUUGCUGUAG	5692	2871
  AD-25959	CAAAUAGAAAAUGGUCCAA	5034	UUGGACCAUUUUCUAUUUG	5693	2993
  AD-25960	AUAGAAAAUGGUCCAAUUA	5035	UAAUUGGACCAUUUUCUAU	5694	2996
  AD-25961	UUUGGGAUAUGUAUGGGUA	5036	UACCCAUACAUAUCCCAAA	5695	3079
  AD-25962	GAUAUGUAUGGGUAGGGUA	5037	UACCCUACCCAUACAUAUC	5696	3084
  AD-25963	UGGGUAGGGUAAAUCAGUA	5038	UACUGAUUUACCCUACCCA	5697	3092
  AD-25964	UAAGAGGUGUUAUUUGGAA	5039	UUCCAAAUAACACCUCUUA	5698	3109
  AD-26017	UGCCUUUUAUCCCAAAGUU	5040	AACUUUGGGAUAAAAGGCA	5699	3152
  AD-26018	UGUUGUAACCUGCUGUGAU	5041	AUCACAGCAGGUUACAACA	5700	3170
  AD-26019	GUUGUAACCUGCUGUGAUA	5042	UAUCACAGCAGGUUACAAC	5701	3171
  AD-26020	CAAGAGAAAAUGCGGUUAU	5043	AUAACCGCAUUUUCUCUUG	5702	3198
  AD-26021	AAGAGAAAAUGCGGUUAUA	5044	UAUAACCGCAUUUUCUCUU	5703	3199
  AD-26022	CCUGUUCCCCUGAGGGUAU	5045	AUACCCUCAGGGGAACAGG	5704	207
  AD-26023	CUGUUCCCCUGAGGGUAUU	5046	AAUACCCUCAGGGGAACAG	5705	208
  AD-26024	CCUGAGGGUAUUUGAAGUA	5047	UACUUCAAAUACCCUCAGG	5706	215
  AD-26025	CUGAGGGUAUUUGAAGUAU	5048	AUACUUCAAAUACCCUCAG	5707	216
  AD-26026	UGAGGGUAUUUGAAGUAUA	5049	UAUACUUCAAAUACCCUCA	5708	217
  AD-26027	GGUAUUUGAAGUAUACCAU	5050	AUGGUAUACUUCAAAUACC	5709	221
  AD-26028	GUAUUUGAAGUAUACCAUA	5051	UAUGGUAUACUUCAAAUAC	5710	222
  AD-26029	UUUGAAGUAUACCAUACAA	5052	UUGUAUGGUAUACUUCAAA	5711	225
  AD-26030	AGUAUACCAUACAACUGUU	5053	AACAGUUGUAUGGUAUACU	5712	230
  AD-26031	GUAUACCAUACAACUGUUU	5054	AAACAGUUGUAUGGUAUAC	5713	231
  AD-26032	UAUACCAUACAACUGUUUU	5055	AAAACAGUUGUAUGGUAUA	5714	232
  AD-26033	ACCAUACAACUGUUUUGAA	5056	UUCAAAACAGUUGUAUGGU	5715	235
  AD-26034	CCAUACAACUGUUUUGAAA	5057	UUUCAAAACAGUUGUAUGG	5716	236
  AD-26035	GAAAAUCCAGCGUGGACAA	5058	UUGUCCACGCUGGAUUUUC	5717	251
  AD-26036	AAAAUCCAGCGUGGACAAU	5059	AUUGUCCACGCUGGAUUUU	5718	252
  AD-26037	CCAGCGUGGACAAUGGCUA	5060	UAGCCAUUGUCCACGCUGG	5719	257
  AD-26038	GUGGACAAUGGCUACUCAA	5061	UUGAGUAGCCAUUGUCCAC	5720	262
  AD-26039	AAUGGCUACUCAAGCUGAU	5062	AUCAGCUUGAGUAGCCAUU	5721	268
  AD-26040	AUGGCUACUCAAGCUGAUU	5063	AAUCAGCUUGAGUAGCCAU	5722	269
  AD-26041	UGGCUACUCAAGCUGAUUU	5064	AAAUCAGCUUGAGUAGCCA	5723	270
  AD-26042	CUACUCAAGCUGAUUUGAU	5065	AUCAAAUCAGCUUGAGUAG	5724	273
  AD-26043	AUUUGAUGGAGUUGGACAU	5066	AUGUCCAACUCCAUCAAAU	5725	285
  AD-26044	UGGAGUUGGACAUGGCCAU	5067	AUGGCCAUGUCCAACUCCA	5726	291
  AD-26045	GUUGGACAUGGCCAUGGAA	5068	UUCCAUGGCCAUGUCCAAC	5727	295
  AD-26046	GCCAUGGAACCAGACAGAA	5069	UUCUGUCUGGUUCCAUGGC	5728	305
  AD-26047	CAUGGAACCAGACAGAAAA	5070	UUUUCUGUCUGGUUCCAUG	5729	307
  AD-26048	GGAGGCGGAGACGGAGGAA	5071	UUCCUCCGUCUCCGCCUCC	5730	111
  AD-26049	AGACAGAAAAGCGGCUGUU	5072	AACAGCCGCUUUUCUGUCU	5731	316
  AD-26050	GACAGAAAAGCGGCUGUUA	5073	UAACAGCCGCUUUUCUGUC	5732	317
  AD-26051	UGUUAGUCACUGGCAGCAA	5074	UUGCUGCCAGUGACUAACA	5733	331
  AD-26052	CACUGGCAGCAACAGUCUU	5075	AAGACUGUUGCUGCCAGUG	5734	338
  AD-26053	ACUGGCAGCAACAGUCUUA	5076	UAAGACUGUUGCUGCCAGU	5735	339
  AD-26054	UCUUACCUGGACUCUGGAA	5077	UUCCAGAGUCCAGGUAAGA	5736	353
  AD-26055	CUUACCUGGACUCUGGAAU	5078	AUUCCAGAGUCCAGGUAAG	5737	354
  AD-26056	CCUGGACUCUGGAAUCCAU	5079	AUGGAUUCCAGAGUCCAGG	5738	358
  AD-26057	GGCUAGUGGUGGACCCCAA	5080	UUGGGGUCCACCACUAGCC	5739	1216
  AD-26058	GCCACUACCACAGCUCCUU	5081	AAGGAGCUGUGGUAGUGGC	5740	383
  AD-26059	UCCUUCUCUGAGUGGUAAA	5082	UUUACCACUCAGAGAAGGA	5741	397
  AD-26060	CUCUGAGUGGUAAAGGCAA	5083	UUGCCUUUACCACUCAGAG	5742	402
  AD-26061	UAAAGGCAAUCCUGAGGAA	5084	UUCCUCAGGAUUGCCUUUA	5743	412
  AD-26062	CAAUCCUGAGGAAGAGGAU	5085	AUCCUCUUCCUCAGGAUUG	5744	418
  AD-26063	UGAGGAAGAGGAUGUGGAU	5086	AUCCACAUCCUCUUCCUCA	5745	424
  AD-26064	AUACCUCCCAAGUCCUGUA	5087	UACAGGACUUGGGAGGUAU	5746	441
  AD-26065	UACCUCCCAAGUCCUGUAU	5088	AUACAGGACUUGGGAGGUA	5747	442
  AD-26066	AGUCCUGUAUGAGUGGGAA	5089	UUCCCACUCAUACAGGACU	5748	451
  AD-26067	UAUGAGUGGGAACAGGGAU	5090	AUCCCUGUUCCCACUCAUA	5749	458
  AD-26068	CAAGCUUUAGUAAAUAUAA	5091	UUAUAUUUACUAAAGCUUG	5750	1232
  AD-26069	AAGCUUUAGUAAAUAUAAU	5092	AUUAUAUUUACUAAAGCUU	5751	1233
  AD-26070	UGAGUGGGAACAGGGAUUU	5093	AAAUCCCUGUUCCCACUCA	5752	460
  AD-26071	GAGUGGGAACAGGGAUUUU	5094	AAAAUCCCUGUUCCCACUC	5753	461
  AD-26072	AGGGAUUUUCUCAGUCCUU	5095	AAGGACUGAGAAAAUCCCU	5754	471
  AD-26073	UUCUCAGUCCUUCACUCAA	5096	UUGAGUGAAGGACUGAGAA	5755	478
  AD-26074	UCAGUCCUUCACUCAAGAA	5097	UUCUUGAGUGAAGGACUGA	5756	481
  AD-26075	CUUCACUCAAGAACAAGUA	5098	UACUUGUUCUUGAGUGAAG	5757	487
  AD-26076	UCAAGAACAAGUAGCUGAU	5099	AUCAGCUACUUGUUCUUGA	5758	493
  AD-26077	CUGAUAUUGAUGGACAGUA	5100	UACUGUCCAUCAAUAUCAG	5759	507
  AD-26078	AUUGAUGGACAGUAUGCAA	5101	UUGCAUACUGUCCAUCAAU	5760	512
  AD-26079	GACUCGAGCUCAGAGGGUA	5102	UACCCUCUGAGCUCGAGUC	5761	532
  AD-26080	CAGAGGGUACGAGCUGCUA	5103	UAGCAGCUCGUACCCUCUG	5762	542
  AD-26081	AGAGGGUACGAGCUGCUAU	5104	AUAGCAGCUCGUACCCUCU	5763	543
  AD-26082	GGGUACGAGCUGCUAUGUU	5105	AACAUAGCAGCUCGUACCC	5764	546
  AD-26083	CUAUGUUCCCUGAGACAUU	5106	AAUGUCUCAGGGAACAUAG	5765	558
  AD-26084	UAUGUUCCCUGAGACAUUA	5107	UAAUGUCUCAGGGAACAUA	5766	559
  AD-26085	GUUCCCUGAGACAUUAGAU	5108	AUCUAAUGUCUCAGGGAAC	5767	562
  AD-26086	UAGAUGAGGGCAUGCAGAU	5109	AUCUGCAUGCCCUCAUCUA	5768	576
  AD-26087	GAGGGCAUGCAGAUCCCAU	5110	AUGGGAUCUGCAUGCCCUC	5769	581
  AD-26088	GGCAUGCAGAUCCCAUCUA	5111	UAGAUGGGAUCUGCAUGCC	5770	584
  AD-26089	AGAUCCCAUCUACACAGUU	5112	AACUGUGUAGAUGGGAUCU	5771	591
  AD-26090	CCCAUCUACACAGUUUGAU	5113	AUCAAACUGUGUAGAUGGG	5772	595
  AD-26091	ACAGUUUGAUGCUGCUCAU	5114	AUGAGCAGCAUCAAACUGU	5773	604
  AD-26092	GAUGCUGCUCAUCCCACUA	5115	UAGUGGGAUGAGCAGCAUC	5774	611
  AD-26093	AUGCUGCUCAUCCCACUAA	5116	UUAGUGGGAUGAGCAGCAU	5775	612
  AD-26094	UGCUGCUCAUCCCACUAAU	5117	AUUAGUGGGAUGAGCAGCA	5776	613
  AD-26095	CCCACUAAUGUCCAGCGUU	5118	AACGCUGGACAUUAGUGGG	5777	623
  AD-26096	CAGCGUUUGGCUGAACCAU	5119	AUGGUUCAGCCAAACGCUG	5778	635
  AD-26097	UGGCUGAACCAUCACAGAU	5120	AUCUGUGAUGGUUCAGCCA	5779	642
  AD-26098	AACCAUCACAGAUGCUGAA	5121	UUCAGCAUCUGUGAUGGUU	5780	648
  AD-26099	ACCAUCACAGAUGCUGAAA	5122	UUUCAGCAUCUGUGAUGGU	5781	649
  AD-26100	AUCACAGAUGCUGAAACAU	5123	AUGUUUCAGCAUCUGUGAU	5782	652
  AD-26101	GAUGCUGAAACAUGCAGUU	5124	AACUGCAUGUUUCAGCAUC	5783	658
  AD-26102	CUGAAACAUGCAGUUGUAA	5125	UUACAACUGCAUGUUUCAG	5784	662
  AD-26103	AACAUGCAGUUGUAAACUU	5126	AAGUUUACAACUGCAUGUU	5785	666
  AD-26104	AUGCAGUUGUAAACUUGAU	5127	AUCAAGUUUACAACUGCAU	5786	669
  AD-26105	UGCAGUUGUAAACUUGAUU	5128	AAUCAAGUUUACAACUGCA	5787	670
  AD-26106	CAGUUGUAAACUUGAUUAA	5129	UUAAUCAAGUUUACAACUG	5788	672
  AD-26107	CUUGAUUAACUAUCAAGAU	5130	AUCUUGAUAGUUAAUCAAG	5789	682
  AD-26108	GAUUAACUAUCAAGAUGAU	5131	AUCAUCUUGAUAGUUAAUC	5790	685
  AD-26109	CUAUCAAGAUGAUGCAGAA	5132	UUCUGCAUCAUCUUGAUAG	5791	691
  AD-26110	GAACUUGCCACACGUGCAA	5133	UUGCACGUGUGGCAAGUUC	5792	707
  AD-26111	AACUUGCCACACGUGCAAU	5134	AUUGCACGUGUGGCAAGUU	5793	708
  AD-26112	CACACGUGCAAUCCCUGAA	5135	UUCAGGGAUUGCACGUGUG	5794	715
  AD-26123	GCAAUCCCUGAACUGACAA	5136	UUGUCAGUUCAGGGAUUGC	5795	722
  AD-26124	CAAUCCCUGAACUGACAAA	5137	UUUGUCAGUUCAGGGAUUG	5796	723
  AD-26125	AAUCCCUGAACUGACAAAA	5138	UUUUGUCAGUUCAGGGAUU	5797	724
  AD-26126	UGAACUGACAAAACUGCUA	5139	UAGCAGUUUUGUCAGUUCA	5798	730
  AD-26127	GAACUGACAAAACUGCUAA	5140	UUAGCAGUUUUGUCAGUUC	5799	731
  AD-26128	AACUGACAAAACUGCUAAA	5141	UUUAGCAGUUUUGUCAGUU	5800	732
  AD-26129	ACUGACAAAACUGCUAAAU	5142	AUUUAGCAGUUUUGUCAGU	5801	733
  AD-26130	GAGGACCAGGUGGUGGUUA	5143	UAACCACCACCUGGUCCUC	5802	755
  AD-26131	AGGACCAGGUGGUGGUUAA	5144	UUAACCACCACCUGGUCCU	5803	756
  AD-26132	GGACCAGGUGGUGGUUAAU	5145	AUUAACCACCACCUGGUCC	5804	757
  AD-26133	GACCAGGUGGUGGUUAAUA	5146	UAUUAACCACCACCUGGUC	5805	758
  AD-26134	UCACUUGCAAUAAUUAUAA	5147	UUAUAAUUAUUGCAAGUGA	5806	1548
  AD-26135	CUUGCAAUAAUUAUAAGAA	5148	UUCUUAUAAUUAUUGCAAG	5807	1551
  AD-26136	ACCAGGUGGUGGUUAAUAA	5149	UUAUUAACCACCACCUGGU	5808	759
  AD-26137	GGCUGCAGUUAUGGUCCAU	5150	AUGGACCAUAACUGCAGCC	5809	778
  AD-26138	GUUAUGGUCCAUCAGCUUU	5151	AAAGCUGAUGGACCAUAAC	5810	785
  AD-26139	AUGGUCCAUCAGCUUUCUA	5152	UAGAAAGCUGAUGGACCAU	5811	788
  AD-26140	UGGUCCAUCAGCUUUCUAA	5153	UUAGAAAGCUGAUGGACCA	5812	789
  AD-26141	UCGGGCUGGUGACAGGGAA	5154	UUCCCUGUCACCAGCCCGA	5813	1624
  AD-26142	GGUCCAUCAGCUUUCUAAA	5155	UUUAGAAAGCUGAUGGACC	5814	790
  AD-26143	GUCCAUCAGCUUUCUAAAA	5156	UUUUAGAAAGCUGAUGGAC	5815	791
  AD-26144	GAAGCUUCCAGACACGCUA	5157	UAGCGUGUCUGGAAGCUUC	5816	812
  AD-26145	AAGCUUCCAGACACGCUAU	5158	AUAGCGUGUCUGGAAGCUU	5817	813
  AD-26146	CUUCCAGACACGCUAUCAU	5159	AUGAUAGCGUGUCUGGAAG	5818	816
  AD-26147	AGACACGCUAUCAUGCGUU	5160	AACGCAUGAUAGCGUGUCU	5819	821
  AD-26148	UCAUGCGUUCUCCUCAGAU	5161	AUCUGAGGAGAACGCAUGA	5820	831
  AD-26149	CCUCAGAUGGUGUCUGCUA	5162	UAGCAGACACCAUCUGAGG	5821	842
  AD-26150	CUCAGAUGGUGUCUGCUAU	5163	AUAGCAGACACCAUCUGAG	5822	843
  AD-26151	GUGUCUGCUAUUGUACGUA	5164	UACGUACAAUAGCAGACAC	5823	851
  AD-26152	CUGCUAUUGUACGUACCAU	5165	AUGGUACGUACAAUAGCAG	5824	855
  AD-26153	UUGUACGUACCAUGCAGAA	5166	UUCUGCAUGGUACGUACAA	5825	861
  AD-26154	UGUACGUACCAUGCAGAAU	5167	AUUCUGCAUGGUACGUACA	5826	862
  AD-26155	CGUACCAUGCAGAAUACAA	5168	UUGUAUUCUGCAUGGUACG	5827	866
  AD-26156	CAUGCAGAAUACAAAUGAU	5169	AUCAUUUGUAUUCUGCAUG	5828	871
  AD-26157	GCAGAAUACAAAUGAUGUA	5170	UACAUCAUUUGUAUUCUGC	5829	874
  AD-26158	GAAUACAAAUGAUGUAGAA	5171	UUCUACAUCAUUUGUAUUC	5830	877
  AD-26159	GAUGUAGAAACAGCUCGUU	5172	AACGAGCUGUUUCUACAUC	5831	887
  AD-26160	GUUGUACCGCUGGGACCUU	5173	AAGGUCCCAGCGGUACAAC	5832	903
  AD-26161	UACCGCUGGGACCUUGCAU	5174	AUGCAAGGUCCCAGCGGUA	5833	907
  AD-26162	CCGCUGGGACCUUGCAUAA	5175	UUAUGCAAGGUCCCAGCGG	5834	909
  AD-26163	UGGGACCUUGCAUAACCUU	5176	AAGGUUAUGCAAGGUCCCA	5835	913
  AD-26164	GGGACCUUGCAUAACCUUU	5177	AAAGGUUAUGCAAGGUCCC	5836	914
  AD-26165	CUUGCAUAACCUUUCCCAU	5178	AUGGGAAAGGUUAUGCAAG	5837	919
  AD-26166	UCUUUAAGUCUGGAGGCAU	5179	AUGCCUCCAGACUUAAAGA	5838	960
  AD-26167	GCAUUCCUGCCCUGGUGAA	5180	UUCACCAGGGCAGGAAUGC	5839	975
  AD-26168	CAUUCCUGCCCUGGUGAAA	5181	UUUCACCAGGGCAGGAAUG	5840	976
  AD-26169	AUUCCUGCCCUGGUGAAAA	5182	UUUUCACCAGGGCAGGAAU	5841	977
  AD-26170	UUCCUGCCCUGGUGAAAAU	5183	AUUUUCACCAGGGCAGGAA	5842	978
  AD-26171	UGCCCUGGUGAAAAUGCUU	5184	AAGCAUUUUCACCAGGGCA	5843	982
  AD-26172	CUGGUGAAAAUGCUUGGUU	5185	AACCAAGCAUUUUCACCAG	5844	986
  AD-26173	GCUUGGUUCACCAGUGGAU	5186	AUCCACUGGUGAACCAAGC	5845	997
  AD-26174	CUUGGUUCACCAGUGGAUU	5187	AAUCCACUGGUGAACCAAG	5846	998
  AD-26175	UGCGUGAGCAGGGUGCCAU	5188	AUGGCACCCUGCUCACGCA	5847	1848
  AD-26176	GCGUGAGCAGGGUGCCAUU	5189	AAUGGCACCCUGCUCACGC	5848	1849
  AD-26177	CACCAGUGGAUUCUGUGUU	5190	AACACAGAAUCCACUGGUG	5849	1005
  AD-26178	CAGUGGAUUCUGUGUUGUU	5191	AACAACACAGAAUCCACUG	5850	1008
  AD-26179	AGUGGAUUCUGUGUUGUUU	5192	AAACAACACAGAAUCCACU	5851	1009
  AD-26180	GUGGAUUCUGUGUUGUUUU	5193	AAAACAACACAGAAUCCAC	5852	1010
  AD-26181	UGGAUUCUGUGUUGUUUUA	5194	UAAAACAACACAGAAUCCA	5853	1011
  AD-26182	GGAUUCUGUGUUGUUUUAU	5195	AUAAAACAACACAGAAUCC	5854	1012
  AD-26183	UGUGUUGUUUUAUGCCAUU	5196	AAUGGCAUAAAACAACACA	5855	1018
  AD-26184	GGGUGGGACACAGCAGCAA	5197	UUGCUGCUGUGUCCCACCC	5856	1927
  AD-26185	GUGUUGUUUUAUGCCAUUA	5198	UAAUGGCAUAAAACAACAC	5857	1019
  AD-26186	UUGUUUUAUGCCAUUACAA	5199	UUGUAAUGGCAUAAAACAA	5858	1022
  AD-26187	CCAUUACAACUCUCCACAA	5200	UUGUGGAGAGUUGUAAUGG	5859	1032
  AD-26188	UACAACUCUCCACAACCUU	5201	AAGGUUGUGGAGAGUUGUA	5860	1036
  AD-26189	ACAACUCUCCACAACCUUU	5202	AAAGGUUGUGGAGAGUUGU	5861	1037
  AD-26190	CAACUCUCCACAACCUUUU	5203	AAAAGGUUGUGGAGAGUUG	5862	1038
  AD-26191	AACUCUCCACAACCUUUUA	5204	UAAAAGGUUGUGGAGAGUU	5863	1039
  AD-26192	ACUCUCCACAACCUUUUAU	5205	AUAAAAGGUUGUGGAGAGU	5864	1040
  AD-26193	CUCUCCACAACCUUUUAUU	5206	AAUAAAAGGUUGUGGAGAG	5865	1041
  AD-26194	UCUCCACAACCUUUUAUUA	5207	UAAUAAAAGGUUGUGGAGA	5866	1042
  AD-26195	CAACCUUUUAUUACAUCAA	5208	UUGAUGUAAUAAAAGGUUG	5867	1048
  AD-26196	CCUUUUAUUACAUCAAGAA	5209	UUCUUGAUGUAAUAAAAGG	5868	1051
  AD-26197	UUACAUCAAGAAGGAGCUA	5210	UAGCUCCUUCUUGAUGUAA	5869	1058
  AD-26198	UACAUCAAGAAGGAGCUAA	5211	UUAGCUCCUUCUUGAUGUA	5870	1059
  AD-26199	CAUCAAGAAGGAGCUAAAA	5212	UUUUAGCUCCUUCUUGAUG	5871	1061
  AD-26200	AUCAAGAAGGAGCUAAAAU	5213	AUUUUAGCUCCUUCUUGAU	5872	1062
  AD-26201	GCUAAAAUGGCAGUGCGUU	5214	AACGCACUGCCAUUUUAGC	5873	1073
  AD-26202	UAAAAUGGCAGUGCGUUUA	5215	UAAACGCACUGCCAUUUUA	5874	1075
  AD-26203	AAAUGGUUGCCUUGCUCAA	5216	UUGAGCAAGGCAACCAUUU	5875	1110
  AD-26204	GCCUGUUCCCCUGAGGGUA	5217	UACCCUCAGGGGAACAGGC	5876	206
  AD-26205	UGGUUGCCUUGCUCAACAA	5218	UUGUUGAGCAAGGCAACCA	5877	1113
  AD-26206	GGUUGCCUUGCUCAACAAA	5219	UUUGUUGAGCAAGGCAACC	5878	1114
  AD-26207	GUUGCCUUGCUCAACAAAA	5220	UUUUGUUGAGCAAGGCAAC	5879	1115
  AD-26208	GCCUUGCUCAACAAAACAA	5221	UUGUUUUGUUGAGCAAGGC	5880	1118
  AD-26209	CCUUGCUCAACAAAACAAA	5222	UUUGUUUUGUUGAGCAAGG	5881	1119
  AD-26210	GUUAAAUUCUUGGCUAUUA	5223	UAAUAGCCAAGAAUUUAAC	5882	1139
  AD-26211	UAUUACGACAGACUGCCUU	5224	AAGGCAGUCUGUCGUAAUA	5883	1153
  AD-26212	AUGGCAACCAAGAAAGCAA	5225	UUGCUUUCUUGGUUGCCAU	5884	1185
  AD-26213	AGUGGUGGACCCCAAGCUU	5226	AAGCUUGGGGUCCACCACU	5885	1220
  AD-26214	GUGGUGGACCCCAAGCUUU	5227	AAAGCUUGGGGUCCACCAC	5886	1221
  AD-26215	UGGUGGACCCCAAGCUUUA	5228	UAAAGCUUGGGGUCCACCA	5887	1222
  AD-26216	UGGACCCCAAGCUUUAGUA	5229	UACUAAAGCUUGGGGUCCA	5888	1225
  AD-26217	GGACCCCAAGCUUUAGUAA	5230	UUACUAAAGCUUGGGGUCC	5889	1226
  AD-26218	GACCCCAAGCUUUAGUAAA	5231	UUUACUAAAGCUUGGGGUC	5890	1227
  AD-26651	ACCCCAAGCUUUAGUAAAU	5232	AUUUACUAAAGCUUGGGGU	5891	1228
  AD-26652	CCCCAAGCUUUAGUAAAUA	5233	UAUUUACUAAAGCUUGGGG	5892	1229
  AD-26653	CCCAAGCUUUAGUAAAUAU	5234	AUAUUUACUAAAGCUUGGG	5893	1230
  AD-26654	CCAAGCUUUAGUAAAUAUA	5235	UAUAUUUACUAAAGCUUGG	5894	1231
  AD-26655	UAAAUAUAAUGAGGACCUA	5236	UAGGUCCUCAUUAUAUUUA	5895	1242
  AD-26656	AAAUAUAAUGAGGACCUAU	5237	AUAGGUCCUCAUUAUAUUU	5896	1243
  AD-26657	AAUAUAAUGAGGACCUAUA	5238	UAUAGGUCCUCAUUAUAUU	5897	1244
  AD-26658	AUAAUGAGGACCUAUACUU	5239	AAGUAUAGGUCCUCAUUAU	5898	1247
  AD-26659	AAACUACUGUGGACCACAA	5240	UUGUGGUCCACAGUAGUUU	5899	1271
  AD-26660	CCACAAGCAGAGUGCUGAA	5241	UUCAGCACUCUGCUUGUGG	5900	1284
  AD-26661	CAGAGUGCUGAAGGUGCUA	5242	UAGCACCUUCAGCACUCUG	5901	1291
  AD-26662	AGAGUGCUGAAGGUGCUAU	5243	AUAGCACCUUCAGCACUCU	5902	1292
  AD-26663	AUUGUAGAAGCUGGUGGAA	5244	UUCCACCAGCUUCUACAAU	5903	1337
  AD-26664	UUGUAGAAGCUGGUGGAAU	5245	AUUCCACCAGCUUCUACAA	5904	1338
  AD-26665	GCUGGUGGAAUGCAAGCUU	5246	AAGCUUGCAUUCCACCAGC	5905	1346
  AD-26666	CUGGUGGAAUGCAAGCUUU	5247	AAAGCUUGCAUUCCACCAG	5906	1347
  AD-26667	AGGACUUCACCUGACAGAU	5248	AUCUGUCAGGUGAAGUCCU	5907	1366
  AD-26668	CUUCACCUGACAGAUCCAA	5249	UUGGAUCUGUCAGGUGAAG	5908	1370
  AD-26669	CCUGACAGAUCCAAGUCAA	5250	UUGACUUGGAUCUGUCAGG	5909	1375
  AD-26670	AGAUCCAAGUCAACGUCUU	5251	AAGACGUUGACUUGGAUCU	5910	1381
  AD-26671	UCCAAGUCAACGUCUUGUU	5252	AACAAGACGUUGACUUGGA	5911	1384
  AD-26672	UCUUGUUCAGAACUGUCUU	5253	AAGACAGUUCUGAACAAGA	5912	1396
  AD-26673	CUUGUUCAGAACUGUCUUU	5254	AAAGACAGUUCUGAACAAG	5913	1397
  AD-26674	GUCUUUGGACUCUCAGGAA	5255	UUCCUGAGAGUCCAAAGAC	5914	1410
  AD-26675	UCUUUGGACUCUCAGGAAU	5256	AUUCCUGAGAGUCCAAAGA	5915	1411
  AD-26676	UUGGACUCUCAGGAAUCUU	5257	AAGAUUCCUGAGAGUCCAA	5916	1414
  AD-26677	UGCCCAGGGAGAACCCCUU	5258	AAGGGGUUCUCCCUGGGCA	5917	2371
  AD-26678	UGGACUCUCAGGAAUCUUU	5259	AAAGAUUCCUGAGAGUCCA	5918	1415
  AD-26679	UCUCAGGAAUCUUUCAGAU	5260	AUCUGAAAGAUUCCUGAGA	5919	1420
  AD-26680	AAUCUUUCAGAUGCUGCAA	5261	UUGCAGCAUCUGAAAGAUU	5920	1427
  AD-26681	CUUUCAGAUGCUGCAACUA	5262	UAGUUGCAGCAUCUGAAAG	5921	1430
  AD-26682	UUCAGAUGCUGCAACUAAA	5263	UUUAGUUGCAGCAUCUGAA	5922	1432
  AD-26683	UGCUGCAACUAAACAGGAA	5264	UUCCUGUUUAGUUGCAGCA	5923	1438
  AD-26684	UAAACAGGAAGGGAUGGAA	5265	UUCCAUCCCUUCCUGUUUA	5924	1447
  AD-26685	AGGGAUGGAAGGUCUCCUU	5266	AAGGAGACCUUCCAUCCCU	5925	1456
  AD-26686	AGGUCUCCUUGGGACUCUU	5267	AAGAGUCCCAAGGAGACCU	5926	1465
  AD-26687	UCUCCUUGGGACUCUUGUU	5268	AACAAGAGUCCCAAGGAGA	5927	1468
  AD-26688	UGGGACUCUUGUUCAGCUU	5269	AAGCUGAACAAGAGUCCCA	5928	1474
  AD-26689	CUUGUUCAGCUUCUGGGUU	5270	AACCCAGAAGCUGAACAAG	5929	1481
  AD-26690	UCAGCUUCUGGGUUCAGAU	5271	AUCUGAACCCAGAAGCUGA	5930	1486
  AD-26691	GCUUCUGGGUUCAGAUGAU	5272	AUCAUCUGAACCCAGAAGC	5931	1489
  AD-26692	CUUCUGGGUUCAGAUGAUA	5273	UAUCAUCUGAACCCAGAAG	5932	1490
  AD-26693	GGCCAGGAUGCCUUGGGUA	5274	UACCCAAGGCAUCCUGGCC	5933	2441
  AD-26694	UUCUGGGUUCAGAUGAUAU	5275	AUAUCAUCUGAACCCAGAA	5934	1491
  AD-26695	CUGGGUUCAGAUGAUAUAA	5276	UUAUAUCAUCUGAACCCAG	5935	1493
  AD-26696	UGGGUUCAGAUGAUAUAAA	5277	UUUAUAUCAUCUGAACCCA	5936	1494
  AD-26697	GUCACCUGUGCAGCUGGAA	5278	UUCCAGCUGCACAGGUGAC	5937	1517
  AD-26698	UCACCUGUGCAGCUGGAAU	5279	AUUCCAGCUGCACAGGUGA	5938	1518
  AD-26699	CACCUGUGCAGCUGGAAUU	5280	AAUUCCAGCUGCACAGGUG	5939	1519
  AD-26700	CUGUGCAGCUGGAAUUCUU	5281	AAGAAUUCCAGCUGCACAG	5940	1522
  AD-26701	UGUGCAGCUGGAAUUCUUU	5282	AAAGAAUUCCAGCUGCACA	5941	1523
  AD-26702	GCAGCUGGAAUUCUUUCUA	5283	UAGAAAGAAUUCCAGCUGC	5942	1526
  AD-26703	CAGCUGGAAUUCUUUCUAA	5284	UUAGAAAGAAUUCCAGCUG	5943	1527
  AD-26704	UUUCUAACCUCACUUGCAA	5285	UUGCAAGUGAGGUUAGAAA	5944	1539
  AD-26705	UUCUAACCUCACUUGCAAU	5286	AUUGCAAGUGAGGUUAGAA	5945	1540
  AD-26706	ACCUCACUUGCAAUAAUUA	5287	UAAUUAUUGCAAGUGAGGU	5946	1545
  AD-26707	CCUCACUUGCAAUAAUUAU	5288	AUAAUUAUUGCAAGUGAGG	5947	1546
  AD-26708	CUCACUUGCAAUAAUUAUA	5289	UAUAAUUAUUGCAAGUGAG	5948	1547
  AD-26709	GUCUGCCAAGUGGGUGGUA	5290	UACCACCCACUUGGCAGAC	5949	1580
  AD-26710	UCUGCCAAGUGGGUGGUAU	5291	AUACCACCCACUUGGCAGA	5950	1581
  AD-26711	GGGUGGUAUAGAGGCUCUU	5292	AAGAGCCUCUAUACCACCC	5951	1591
  AD-26712	AUAGAGGCUCUUGUGCGUA	5293	UACGCACAAGAGCCUCUAU	5952	1598
  AD-26713	UCUUGUGCGUACUGUCCUU	5294	AAGGACAGUACGCACAAGA	5953	1606
  AD-26714	CUGGUGACAGGGAAGACAU	5295	AUGUCUUCCCUGUCACCAG	5954	1629
  AD-26715	ACAUCACUGAGCCUGCCAU	5296	AUGGCAGGCUCAGUGAUGU	5955	1644
  AD-26716	GCCUGCCAUCUGUGCUCUU	5297	AAGAGCACAGAUGGCAGGC	5956	1654
  AD-26717	UCUGACCAGCCGACACCAA	5298	UUGGUGUCGGCUGGUCAGA	5957	1678
  AD-26718	GACCAGCCGACACCAAGAA	5299	UUCUUGGUGUCGGCUGGUC	5958	1681
  AD-26719	GACACCAAGAAGCAGAGAU	5300	AUCUCUGCUUCUUGGUGUC	5959	1689
  AD-26720	AGCAGAGAUGGCCCAGAAU	5301	AUUCUGGGCCAUCUCUGCU	5960	1699
  AD-26721	GAUGGCCCAGAAUGCAGUU	5302	AACUGCAUUCUGGGCCAUC	5961	1705
  AD-26722	CCAGAAUGCAGUUCGCCUU	5303	AAGGCGAACUGCAUUCUGG	5962	1711
  AD-26723	AUGCAGUUCGCCUUCACUA	5304	UAGUGAAGGCGAACUGCAU	5963	1716
  AD-26724	UGCAGUUCGCCUUCACUAU	5305	AUAGUGAAGGCGAACUGCA	5964	1717
  AD-26725	UCGCCUUCACUAUGGACUA	5306	UAGUCCAUAGUGAAGGCGA	5965	1723
  AD-26726	UCACUAUGGACUACCAGUU	5307	AACUGGUAGUCCAUAGUGA	5966	1729
  AD-26727	UGGACUACCAGUUGUGGUU	5308	AACCACAACUGGUAGUCCA	5967	1735
  AD-26728	GGACUACCAGUUGUGGUUA	5309	UAACCACAACUGGUAGUCC	5968	1736
  AD-26729	GACUACCAGUUGUGGUUAA	5310	UUAACCACAACUGGUAGUC	5969	1737
  AD-26730	CAGUUGUGGUUAAGCUCUU	5311	AAGAGCUUAACCACAACUG	5970	1743
  AD-26731	AGUUGUGGUUAAGCUCUUA	5312	UAAGAGCUUAACCACAACU	5971	1744
  AD-26732	AAGCUCUUACACCCACCAU	5313	AUGGUGGGUGUAAGAGCUU	5972	1754
  AD-26733	CAUCCCACUGGCCUCUGAU	5314	AUCAGAGGCCAGUGGGAUG	5973	1770
  AD-26734	AUCCCACUGGCCUCUGAUA	5315	UAUCAGAGGCCAGUGGGAU	5974	1771
  AD-26735	UCCCACUGGCCUCUGAUAA	5316	UUAUCAGAGGCCAGUGGGA	5975	1772
  AD-26736	UGGCCUCUGAUAAAGGCUA	5317	UAGCCUUUAUCAGAGGCCA	5976	1778
  AD-26737	UCUGAUAAAGGCUACUGUU	5318	AACAGUAGCCUUUAUCAGA	5977	1783
  AD-26738	AUAAAGGCUACUGUUGGAU	5319	AUCCAACAGUAGCCUUUAU	5978	1787
  AD-26739	GGCUACUGUUGGAUUGAUU	5320	AAUCAAUCCAACAGUAGCC	5979	1792
  AD-26740	UGUUGGAUUGAUUCGAAAU	5321	AUUUCGAAUCAAUCCAACA	5980	1798
  AD-26741	UGCCAUUCCACGACUAGUU	5322	AACUAGUCGUGGAAUGGCA	5981	1861
  AD-26742	UUCCACGACUAGUUCAGUU	5323	AACUGAACUAGUCGUGGAA	5982	1866
  AD-26743	ACGACUAGUUCAGUUGCUU	5324	AAGCAACUGAACUAGUCGU	5983	1870
  AD-26744	ACUAGUUCAGUUGCUUGUU	5325	AACAAGCAACUGAACUAGU	5984	1873
  AD-26745	GUUGCUUGUUCGUGCACAU	5326	AUGUGCACGAACAAGCAAC	5985	1882
  AD-26746	UGUUCGUGCACAUCAGGAU	5327	AUCCUGAUGUGCACGAACA	5986	1888
  AD-26747	GUUCGUGCACAUCAGGAUA	5328	UAUCCUGAUGUGCACGAAC	5987	1889
  AD-26748	GGUGGGACACAGCAGCAAU	5329	AUUGCUGCUGUGUCCCACC	5988	1928
  AD-26749	GUGGGACACAGCAGCAAUU	5330	AAUUGCUGCUGUGUCCCAC	5989	1929
  AD-26750	UGGGACACAGCAGCAAUUU	5331	AAAUUGCUGCUGUGUCCCA	5990	1930
  AD-26751	GGGGUCCGCAUGGAAGAAA	5332	UUUCUUCCAUGCGGACCCC	5991	1955
  AD-26752	GGGUCCGCAUGGAAGAAAU	5333	AUUUCUUCCAUGCGGACCC	5992	1956
  AD-26753	UCACAUCCUAGCUCGGGAU	5334	AUCCCGAGCUAGGAUGUGA	5993	1999
  AD-26754	CAUCCUAGCUCGGGAUGUU	5335	AACAUCCCGAGCUAGGAUG	5994	2002
  AD-26755	UAGCUCGGGAUGUUCACAA	5336	UUGUGAACAUCCCGAGCUA	5995	2007
  AD-26756	GGGAUGUUCACAACCGAAU	5337	AUUCGGUUGUGAACAUCCC	5996	2013
  AD-26757	GGAUGUUCACAACCGAAUU	5338	AAUUCGGUUGUGAACAUCC	5997	2014
  AD-26758	CAGAGGACUAAAUACCAUU	5339	AAUGGUAUUUAGUCCUCUG	5998	2038
  AD-26759	GGACUAAAUACCAUUCCAU	5340	AUGGAAUGGUAUUUAGUCC	5999	2042
  AD-26760	UAAAUACCAUUCCAUUGUU	5341	AACAAUGGAAUGGUAUUUA	6000	2046
  AD-26761	AAAUACCAUUCCAUUGUUU	5342	AAACAAUGGAAUGGUAUUU	6001	2047
  AD-26762	AUUGUUUGUGCAGCUGCUU	5343	AAGCAGCUGCACAAACAAU	6002	2059
  AD-26763	UUGUUUGUGCAGCUGCUUU	5344	AAAGCAGCUGCACAAACAA	6003	2060
  AD-26764	UGUUUGUGCAGCUGCUUUA	5345	UAAAGCAGCUGCACAAACA	6004	2061
  AD-26765	GUUUGUGCAGCUGCUUUAU	5346	AUAAAGCAGCUGCACAAAC	6005	2062
  AD-26766	UUUGUGCAGCUGCUUUAUU	5347	AAUAAAGCAGCUGCACAAA	6006	2063
  AD-26767	AGCUGCUUUAUUCUCCCAU	5348	AUGGGAGAAUAAAGCAGCU	6007	2070
  AD-26768	GCUGCUUUAUUCUCCCAUU	5349	AAUGGGAGAAUAAAGCAGC	6008	2071
  AD-26769	UUUAUUCUCCCAUUGAAAA	5350	UUUUCAAUGGGAGAAUAAA	6009	2076
  AD-26770	AUUCUCCCAUUGAAAACAU	5351	AUGUUUUCAAUGGGAGAAU	6010	2079
  AD-26771	UCCCAUUGAAAACAUCCAA	5352	UUGGAUGUUUUCAAUGGGA	6011	2083
  AD-26772	UGCAGGGGUCCUCUGUGAA	5353	UUCACAGAGGACCCCUGCA	6012	2110
  AD-26773	ACUUGCUCAGGACAAGGAA	5354	UUCCUUGUCCUGAGCAAGU	6013	2128
  AD-26774	CAGCUCCUCUGACAGAGUU	5355	AACUCUGUCAGAGGAGCUG	6014	2178
  AD-26775	AGCUCCUCUGACAGAGUUA	5356	UAACUCUGUCAGAGGAGCU	6015	2179
  AD-26776	UCCUCUGACAGAGUUACUU	5357	AAGUAACUCUGUCAGAGGA	6016	2182
  AD-26777	ACAGAGUUACUUCACUCUA	5358	UAGAGUGAAGUAACUCUGU	6017	2189
  AD-26778	AGUUACUUCACUCUAGGAA	5359	UUCCUAGAGUGAAGUAACU	6018	2193
  AD-26779	GUUACUUCACUCUAGGAAU	5360	AUUCCUAGAGUGAAGUAAC	6019	2194
  AD-26780	ACUUCACUCUAGGAAUGAA	5361	UUCAUUCCUAGAGUGAAGU	6020	2197
  AD-26781	GCUGCUGUUUUGUUCCGAA	5362	UUCGGAACAAAACAGCAGC	6021	2234
  AD-26782	CUGCUGUUUUGUUCCGAAU	5363	AUUCGGAACAAAACAGCAG	6022	2235
  AD-26783	GUCUGAGGACAAGCCACAA	5364	UUGUGGCUUGUCCUCAGAC	6023	2254
  AD-26784	UGAGGACAAGCCACAAGAU	5365	AUCUUGUGGCUUGUCCUCA	6024	2257
  AD-26785	ACAAGCCACAAGAUUACAA	5366	UUGUAAUCUUGUGGCUUGU	6025	2262
  AD-26786	AGCCACAAGAUUACAAGAA	5367	UUCUUGUAAUCUUGUGGCU	6026	2265
  AD-26787	AGAUUACAAGAAACGGCUU	5368	AAGCCGUUUCUUGUAAUCU	6027	2272
  AD-26788	CAAGAAACGGCUUUCAGUU	5369	AACUGAAAGCCGUUUCUUG	6028	2278
  AD-26789	AGCUGACCAGCUCUCUCUU	5370	AAGAGAGAGCUGGUCAGCU	6029	2298
  AD-26790	ACCAGCUCUCUCUUCAGAA	5371	UUCUGAAGAGAGAGCUGGU	6030	2303
  AD-26791	UAUUGGUGCCCAGGGAGAA	5372	UUCUCCCUGGGCACCAAUA	6031	2365
  AD-26792	CAGGGAGAACCCCUUGGAU	5373	AUCCAAGGGGUUCUCCCUG	6032	2375
  AD-26793	AGGGAGAACCCCUUGGAUA	5374	UAUCCAAGGGGUUCUCCCU	6033	2376
  AD-26794	CCUUGGAUAUCGCCAGGAU	5375	AUCCUGGCGAUAUCCAAGG	6034	2386
  AD-26795	UAUCGCCAGGAUGAUCCUA	5376	UAGGAUCAUCCUGGCGAUA	6035	2393
  AD-26796	GCCAGGAUGAUCCUAGCUA	5377	UAGCUAGGAUCAUCCUGGC	6036	2397
  AD-26797	CCAGGAUGAUCCUAGCUAU	5378	AUAGCUAGGAUCAUCCUGG	6037	2398
  AD-26798	GAUGAUCCUAGCUAUCGUU	5379	AACGAUAGCUAGGAUCAUC	6038	2402
  AD-26799	AUCCUAGCUAUCGUUCUUU	5380	AAAGAACGAUAGCUAGGAU	6039	2406
  AD-26800	UCCUAGCUAUCGUUCUUUU	5381	AAAAGAACGAUAGCUAGGA	6040	2407
  AD-26801	UCUUUUCACUCUGGUGGAU	5382	AUCCACCAGAGUGAAAAGA	6041	2420
  AD-26802	CUUUUCACUCUGGUGGAUA	5383	UAUCCACCAGAGUGAAAAG	6042	2421
  AD-26803	UUUUCACUCUGGUGGAUAU	5384	AUAUCCACCAGAGUGAAAA	6043	2422
  AD-26804	UGGUGGAUAUGGCCAGGAU	5385	AUCCUGGCCAUAUCCACCA	6044	2431
  AD-26805	GAUAUGGCCAGGAUGCCUU	5386	AAGGCAUCCUGGCCAUAUC	6045	2436
  AD-26806	CCUUGGGUAUGGACCCCAU	5387	AUGGGGUCCAUACCCAAGG	6046	2451
  AD-26807	UGGGUAUGGACCCCAUGAU	5388	AUCAUGGGGUCCAUACCCA	6047	2454
  AD-26808	UUGUAAACUUGAUUAACUA	5389	UAGUUAAUCAAGUUUACAA	6048	675
  AD-26809	UGUAAACUUGAUUAACUAU	5390	AUAGUUAAUCAAGUUUACA	6049	676
  AD-26810	AAACUUGAUUAACUAUCAA	5391	UUGAUAGUUAAUCAAGUUU	6050	679
  AD-26811	UAUGGACCCCAUGAUGGAA	5392	UUCCAUCAUGGGGUCCAUA	6051	2458
  AD-26812	GGACCCCAUGAUGGAACAU	5393	AUGUUCCAUCAUGGGGUCC	6052	2461
  AD-26813	CCAUGAUGGAACAUGAGAU	5394	AUCUCAUGUUCCAUCAUGG	6053	2466
  AD-26814	ACCACCCUGGUGCUGACUA	5395	UAGUCAGCACCAGGGUGGU	6054	2493
  AD-26815	CCACCCUGGUGCUGACUAU	5396	AUAGUCAGCACCAGGGUGG	6055	2494
  AD-26816	UGCUGACUAUCCAGUUGAU	5397	AUCAACUGGAUAGUCAGCA	6056	2503
  AD-26817	AGUUGAUGGGCUGCCAGAU	5398	AUCUGGCAGCCCAUCAACU	6057	2515
  AD-26818	UGCCCAGGACCUCAUGGAU	5399	AUCCAUGAGGUCCUGGGCA	6058	2542
  AD-26819	GCAAUCAGCUGGCCUGGUU	5400	AACCAGGCCAGCUGAUUGC	6059	2580
  AD-26820	CAAUCAGCUGGCCUGGUUU	5401	AAACCAGGCCAGCUGAUUG	6060	2581
  AD-26821	GGUUUGAUACUGACCUGUA	5402	UACAGGUCAGUAUCAAACC	6061	2595
  AD-26822	AUACUGACCUGUAAAUCAU	5403	AUGAUUUACAGGUCAGUAU	6062	2601
  AD-26823	UGACCUGUAAAUCAUCCUU	5404	AAGGAUGAUUUACAGGUCA	6063	2605
  AD-26824	GACCUGUAAAUCAUCCUUU	5405	AAAGGAUGAUUUACAGGUC	6064	2606
  AD-26825	ACCUGUAAAUCAUCCUUUA	5406	UAAAGGAUGAUUUACAGGU	6065	2607
  AD-26826	AAUACAAAUGAUGUAGAAA	5407	UUUCUACAUCAUUUGUAUU	6066	878
  AD-26900	UUUUAAGAAUAUCUGUAAU	5408	AUUACAGAUAUUCUUAAAA	6067	2745
  AD-26901	UACAGCAAUUUCUAAUUUU	5409	AAAAUUAGAAAUUGCUGUA	6068	2872
  AD-26902	CACUAAUUCAUAAUCACUC	5410	GAGUGAUUAUGAAUUAGUG	6069	2915
  AD-26903	ACUAAUUCAUAAUCACUCU	5411	AGAGUGAUUAUGAAUUAGU	6070	2916
  AD-26904	UAAUUCAUAAUCACUCUAA	5412	UUAGAGUGAUUAUGAAUUA	6071	2918
  AD-26905	AAUUCAUAAUCACUCUAAU	5413	AUUAGAGUGAUUAUGAAUU	6072	2919
  AD-26906	AAUUGUAAUCUGAAUAAAG	5414	CUUUAUUCAGAUUACAAUU	6073	2939
  AD-26907	UUUGUAUAAAAUAGACAAA	5415	UUUGUCUAUUUUAUACAAA	6074	2978
  AD-26908	UUGUAUAAAAUAGACAAAU	5416	AUUUGUCUAUUUUAUACAA	6075	2979
  AD-26909	UGUAUAAAAUAGACAAAUA	5417	UAUUUGUCUAUUUUAUACA	6076	2980
  AD-26910	GUAUAAAAUAGACAAAUAG	5418	CUAUUUGUCUAUUUUAUAC	6077	2981
  AD-26911	AUAAAAUAGACAAAUAGAA	5419	UUCUAUUUGUCUAUUUUAU	6078	2983
  AD-26912	UAAAAUAGACAAAUAGAAA	5420	UUUCUAUUUGUCUAUUUUA	6079	2984
  AD-26913	AAAUAGACAAAUAGAAAAU	5421	AUUUUCUAUUUGUCUAUUU	6080	2986
  AD-26914	UGGGAUAUGUAUGGGUAGG	5422	CCUACCCAUACAUAUCCCA	6081	3081
  AD-26915	GGGAUAUGUAUGGGUAGGG	5423	CCCUACCCAUACAUAUCCC	6082	3082
  AD-26916	CUAAUUCAUAAUCACUCUA	5424	UAGAGUGAUUAUGAAUUAG	6083	2917
  AD-26917	AAAUAGAAAAUGGUCCAAU	5425	AUUGGACCAUUUUCUAUUU	6084	2994
  AD-26918	AAUAGAAAAUGGUCCAAUU	5426	AAUUGGACCAUUUUCUAUU	6085	2995
  AD-26919	UUUGGACAGUUUACCAGUU	5427	AACUGGUAAACUGUCCAAA	6086	3134
  AD-26920	AUUCUUUCUAACCUCACUU	5428	AAGUGAGGUUAGAAAGAAU	6087	1535
  AD-26921	UGGAUUGAUUCGAAAUCUU	5429	AAGAUUUCGAAUCAAUCCA	6088	1801
  SET1_1245	GACCCCAAGCUUUAGUAAA	6090	UUUACUAAAGCUUGGGGUC	6111	1227
  SET1_1249	CCAAGCUUUAGUAAAUAUA	6091	UAUAUUUACUAAAGCUUGG	6112	1231
  SET1_1250	CAAGCUUUAGUAAAUAUAA	6092	UUAUAUUUACUAAAGCUUG	6113	1232
  SET1_1450	UUCAGAUGCUGCAACUAAA	6093	UUUAGUUGCAGCAUCUGAA	6114	1432
  SET1_1545	CAGCUGGAAUUCUUUCUAA	6094	UUAGAAAGAAUUCCAGCUG	6115	1527
  SET1_1755	GACUACCAGUUGUGGUUAA	6095	UUAACCACAACUGGUAGUC	6116	1737
  SET1_1814	ACUGUUGGAUUGAUUCGAA	6096	UUCGAAUCAAUCCAACAGU	6117	1796
  SET1_1816	UGUUGGAUUGAUUCGAAAU	6097	AUUUCGAAUCAAUCCAACA	6118	1798
  SET1_1974	GGGUCCGCAUGGAAGAAAU	6098	AUUUCUUCCAUGCGGACCC	6119	1956
  SET1_2202	CUCUGACAGAGUUACUUCA	6099	UGAAGUAACUCUGUCAGAG	6120	2184
  SET1_2425	UCCUAGCUAUCGUUCUUUU	6100	AAAAGAACGAUAGCUAGGA	6121	2407
  SET1_254	CCAUACAACUGUUUUGAAA	6101	UUUCAAAACAGUUGUAUGG	6122	236
  SET1_3146	AAGUGAAGAAUGCACAAGA	6102	UCUUGUGCAUUCUUCACUU	6123	3128
  SET1_3169	AUCACAAGAUGGAAUUUAU	6103	AUAAAUUCCAUCUUGUGAU	6124	3151
  SET1_3196	AGCCUUGCUUGUUAAAUUU	6104	AAAUUUAACAAGCAAGGCU	6125	3178
  SET1_3477	AAUAGAAAAUGGUCCAAUU	6105	AAUUGGACCAUUUUCUAUU	6126	3459
  SET1_703	GAUUAACUAUCAAGAUGAU	6106	AUCAUCUUGAUAGUUAAUC	6127	685
  SET1_709	CUAUCAAGAUGAUGCAGAA	6107	UUCUGCAUCAUCUUGAUAG	6128	691
  SET1_865	GAUGGUGUCUGCUAUUGUA	6108	UACAAUAGCAGACACCAUC	6129	847
  SET1_889	CAUGCAGAAUACAAAUGAU	6109	AUCAUUUGUAUUCUGCAUG	6130	871
  SET1_895	GAAUACAAAUGAUGUAGAA	6110	UUCUACAUCAUUUGUAUUC	6131	877

• Modified sequences are listed in Table 3; the specific modifications are disclosed herein. The sequences in Table 2 correspond to portions of the wild-type Beta-Catenin gene without modifications or dTdT extensions. The positions are also provided. In the sequences in these tables, lower-case letters (e.g., c, u) indicate modified nucleotides while upper case letters (e.g., C, U, A, G) indicate unmodified nucleotides. In Table 3, modified versions of the sequences are shown. However, the present disclosure encompasses unmodified versions of these sequences and other versions which comprise additional or alternative modifications. Thus, for example, AD-18892 can optionally have the unmodified sequence uGGuGcuGAcuAuccAGuu (SEQ ID NO: 429) in the sense strand and AACUGGAuAGUcAGcACcA (SEQ ID NO: 430) in the anti-sense strand. The present disclosure also encompasses alternative modified versions of the duplex comprising uGGuGcuGAcuAuccAGuu (SEQ ID NO: 429) in the sense strand and AACUGGAuAGUcAGcACcA (SEQ ID NO: 430) in the anti-sense strand.
• In the sequences in Tables 1, 2 and 3, the modified and unmodified sequences can optionally comprise the sequence “dTsdT” or “UU” at the 3′ end. In the sequences disclosed herein, the TT and UU dinucleotides were not in the inverted/reverse orientation and “UU” is 2′-OMe-U 2′-OMe-U.
• Thus, for example, AD-18892 can optionally have the modified sequence uGGuGcuGAcuAuccAGuudTdT (SEQ ID NO: 6132) or uGGuGcuGAcuAuccAGuudTsdT (SEQ ID NO: 6133) in the sense strand; and AACUGGAuAGUcAGcACcAdTdT (SEQ ID NO: 6134) or AACUGGAuAGUcAGcACcAdTsdT (SEQ ID NO: 6135) in the anti-sense strand. As noted in Table 3, below, dT is 2′-deoxy-thymidine-5′-phosphate and sdT is 2′-deoxy Thymidine 5′-phosphorothioate.
• In several sequences in this Table, the nickname “Set1_#” can be preceded by the prefix “hsCTNNB1_”. Thus “Set1_254” is also designated “hsCTNNB1_Set1_254”. The number is derived from one type of calculation of the position on the gene. Thus, the designations Set1_1245, Set1_1249, Set1_1250, Set1_1450, Set1_1545, Set1_1755, Set1_1814, Set1_1816, Set1_1974, Set1_2202, Set1_2425, Set1254, Set1_3146, Set1_3169, Set1_3196, Set1_3477, Set1_703, Set1_709, Set1_865, Set1_889, Set1_895 indicate duplexes (or modified variants thereof) which correspond to one type of calculation of the positions 1245, 1249, 1250, 1450, 1545, 1755, 1814, 1816, 1974, 2202, 2425, 254, 3146, 3169, 3196, 3477, 703, 709, 865, 889, 895, respectively. However, these positions were calculated using different parameters than other sequences in this Table, resulting in a 18 nt shift. Thus, “Set1_254” pertains to a sequence which corresponds to position 236. Also note that the underscore (_) is sometimes replaced by a space ( ); thus, for example, “Set1_3169” is the same as “Set1_3169”; and “hsCTNNB1_Set2_254_A48_S26” is the same as “hsCTNNB1 Set2 254 A48 S26”.
• In addition, additional suffices can be appended to the nickname to designate different variants which have the same sequence (e.g., the same sequence of nucleotides), but different modifications. Thus, assorted variants of duplexes within “hsCTNNB1_Set1_1245” include, inter alia: hsCTNNB1_Set1254A22S26; hsCTNNB1_Set1254A25S27; hsCTNNB1_Set1_254A_LO_V1_S26; hsCTNNB1_Set1_254_A_LO_V2_S_LO_V1; hsCTNNB1_Set2_254A_LO_V3S_LO_V2; hsCTNNB1_Set2_254A_LO_V4_S_LO_V1; hsCTNNB1_Set2_254A_LO_V5S_LO_V1; and hsCTNNB1_Set2_254_A48_S26.

• TABLE 3
  Beta-Catenin RNAi agents: Example Modified Sequences

  			Sense		Anti-
  			SEQ		sense
  			ID		SEQ ID
  	Duplex	Sense Sequence	NO:	Anti-sense Sequence	NO:	Position
  	AD-18892	uGGuGcuGAcuAuccAGuu	1	AACUGGAuAGUcAGcACcA	6497	2500
  	AD-18893	ccAucuGuGcucuucGucA	2	UGACGAAGAGcAcAGAUGG	661	1659
  	AD-18894	AuAAGcAGGuGGAucuAuu	3	AAuAGAUCcACCUGCUuAU	662	3038
  	AD-18895	AuccAAAGAGuAGcuGcAG	4	CUGcAGCuACUCUUUGGAU	663	2096
  	AD-18896	GAcAAuGGcuAcucAAGcu	5	AGCUUGAGuAGCcAUUGUC	664	265
  	AD-18897	cuGuuGGAuuGAuucGAAA	6	UUUCGAAUcAAUCcAAcAG	665	1797
  	AD-18898	GcuGGccuGGuuuGAuAcu	7	AGuAUcAAACcAGGCcAGC	666	2587
  	AD-18899	ucuAAccucAcuuGcAAuA	8	uAUUGcAAGUGAGGUuAGA	667	1541
  	AD-18900	GAuAucGccAGGAuGAucc	9	GGAUcAUCCUGGCGAuAUC	668	2391
  	AD-18901	uGGccAucuuuAAGucuGG	10	CcAGACUuAAAGAUGGCcA	669	954
  	AD-18902	uGuAGAAcAcuAAuucAuA	11	uAUGAAUuAGUGUUCuAcA	670	2908
  	AD-18903	AucAGuAAGAGGuGuuAuu	12	AAuAAcACCUCUuACUGAU	671	3104
  	AD-18904	GuGcucuucGucAucuGAc	13	GUcAGAUGACGAAGAGcAC	672	1665
  	AD-18905	uGGuuuGAuAcuGAccuGu	14	AcAGGUcAGuAUcAAACcA	673	2594
  	AD-18906	ccAGuuGccuuuuAucccA	15	UGGGAuAAAAGGcAACUGG	674	3147
  	AD-18907	ccuGGuuuGAuAcuGAccu	16	AGGUcAGuAUcAAACcAGG	675	2592
  	AD-18908	GAcuAuccAGuuGAuGGGc	17	GCCcAUcAACUGGAuAGUC	676	2507
  	AD-18909	AGccAAuGGcuuGGAAuGA	18	UcAUUCcAAGCcAUUGGCU	677	2325
  	AD-18910	GccAAuGGcuuGGAAuGAG	19	CUcAUUCcAAGCcAUUGGC	678	2326
  	AD-18911	AGAuGAGGGcAuGcAGAuc	20	GAUCUGcAUGCCCUcAUCU	679	577
  	AD-18912	GGuccucuGuGAAcuuGcu	21	AGcAAGUUcAcAGAGGACC	680	2116
  	AD-18913	AAcccuAGccuuGcuuGuu	22	AAcAAGcAAGGCuAGGGUU	681	2708
  	AD-18914	GAAcAcuAAuucAuAAucA	23	UGAUuAUGAAUuAGUGUUC	682	2912
  	AD-18915	AucAAAcccuAGccuuGcu	24	AGcAAGGCuAGGGUUUGAU	683	2704
  	AD-18916	AccAGuuGccuuuuAuccc	25	GGGAuAAAAGGcAACUGGU	684	3146
  	AD-18917	cuAAccucAcuuGcAAuAA	26	UuAUUGcAAGUGAGGUuAG	685	1542
  	AD-18918	AucccAcuAAuGuccAGcG	27	CGCUGGAcAUuAGUGGGAU	686	621
  	AD-18919	cuGAcuAuccAGuuGAuGG	28	CcAUcAACUGGAuAGUcAG	687	2505
  	AD-18920	GGccuGGuuuGAuAcuGAc	29	GUcAGuAUcAAACcAGGCC	688	2590
  	AD-18921	GGuAAAucAGuAAGAGGuG	30	cACCUCUuACUGAUUuACC	689	3099
  	AD-18922	GccuGGuuuGAuAcuGAcc	31	GGUcAGuAUcAAACcAGGC	690	2591
  	AD-18923	cAGGGGuccucuGuGAAcu	32	AGUUcAcAGAGGACCCCUG	691	2112
  	AD-18925	cuGGAAuccAuucuGGuGc	33	GcACcAGAAUGGAUUCcAG	692	366
  	AD-18926	uGAGAuGGGuGGccAccAc	34	GUGGUGGCcACCcAUCUcA	693	2479
  	AD-18927	GAuGAuAuAAAuGuGGucA	35	UGACcAcAUUuAuAUcAUC	694	1502
  	AD-18928	uGcuuuAuucucccAuuGA	36	UcAAUGGGAGAAuAAAGcA	695	2073
  	AD-18929	uuAucAAAcccuAGccuuG	37	cAAGGCuAGGGUUUGAuAA	696	2702
  	AD-18930	ccAcuGGccucuGAuAAAG	38	CUUuAUcAGAGGCcAGUGG	697	1774
  	AD-18931	AAcuuGccAcAcGuGcAAu	39	AUUGcACGUGUGGcAAGUU	698	708
  	AD-18932	GcucuucGucAucuGAccA	40	UGGUcAGAUGACGAAGAGC	699	1667
  	AD-18933	GuAAcAAuAcAAAuGGAuu	41	AAUCcAUUUGuAUUGUuAC	700	2629
  	AD-18934	GGGGuccucuGuGAAcuuG	42	cAAGUUcAcAGAGGACCCC	701	2114
  	AD-18935	cAAAcccuAGccuuGcuuG	43	cAAGcAAGGCuAGGGUUUG	702	2706
  	AD-18936	GAGuAAuGGuGuAGAAcAc	44	GUGUUCuAcACcAUuACUC	703	2899
  	AD-18937	GGAAGAcAucAcuGAGccu	45	AGGCUcAGUGAUGUCUUCC	704	1639
  	AD-18938	GGGAAGAcAucAcuGAGcc	46	GGCUcAGUGAUGUCUUCCC	705	1638
  	AD-18939	GGuGuAGAAcAcuAAuucA	47	UGAAUuAGUGUUCuAcACC	706	2906
  	AD-18940	uAccAGuuGccuuuuAucc	48	GGAuAAAAGGcAACUGGuA	707	3145
  	AD-18941	GGAuAucGccAGGAuGAuc	49	GAUcAUCCUGGCGAuAUCC	708	2390
  	AD-18942	AAAcccuAGccuuGcuuGu	50	AcAAGcAAGGCuAGGGUUU	709	2707
  	AD-18943	cucuucGucAucuGAccAG	51	CUGGUcAGAUGACGAAGAG	710	1668
  	AD-18944	uGAcuAuccAGuuGAuGGG	52	CCcAUcAACUGGAuAGUcA	711	2506
  	AD-18945	AcAAGcAGAGuGcuGAAGG	53	CCUUcAGcACUCUGCUUGU	712	1286
  	AD-18946	cAucuGuGcucuucGucAu	54	AUGACGAAGAGcAcAGAUG	713	1660
  	AD-18947	cAAuGGcuuGGAAuGAGAc	55	GUCUcAUUCcAAGCcAUUG	714	2328
  	AD-18948	AcuGGccucuGAuAAAGGc	56	GCCUUuAUcAGAGGCcAGU	715	1776
  	AD-18949	ucAucccAcuAAuGuccAG	57	CUGGAcAUuAGUGGGAUGA	716	619
  	AD-18950	AAAAGGAAGcuuccAGAcA	58	UGUCUGGAAGCUUCCUUUU	717	807
  	AD-18951	cGuucuuuucAcucuGGuG	59	cACcAGAGUGAAAAGAACG	718	2417
  	AD-18952	AAAGuuGuuGuAAccuGcu	60	AGcAGGUuAcAAcAACUUU	719	3165
  	AD-18953	AcAAuGGcuAcucAAGcuG	61	cAGCUUGAGuAGCcAUUGU	720	266
  	AD-18954	cucAucccAcuAAuGuccA	62	UGGAcAUuAGUGGGAUGAG	721	618
  	AD-18955	AGGGGuccucuGuGAAcuu	63	AAGUUcAcAGAGGACCCCU	722	2113
  	AD-18956	AAGcAGGuGGAucuAuuuc	64	GAAAuAGAUCcACCUGCUU	723	3040
  	AD-18957	AAGuuGuuGuAAccuGcuG	65	cAGcAGGUuAcAAcAACUU	724	3166
  	AD-18958	AGcAGGuGGAucuAuuucA	66	UGAAAuAGAUCcACCUGCU	725	3041
  	AD-18959	AGGGcAuGcAGAucccAuc	67	GAUGGGAUCUGcAUGCCCU	726	582
  	AD-18960	AAAuGGuucAGAAuuAAAc	68	GUUuAAUUCUGAACcAUUU	727	3220
  	AD-18961	uGAAcuuGcucAGGAcAAG	69	CUUGUCCUGAGcAAGUUcA	728	2125
  	AD-18962	AAGAGuAGcuGcAGGGGuc	70	GACCCCUGcAGCuACUCUU	729	2101
  	AD-18963	cccAcuGGccucuGAuAAA	71	UUuAUcAGAGGCcAGUGGG	730	1773
  	AD-18964	cuGGccuGGuuuGAuAcuG	72	cAGuAUcAAACcAGGCcAG	731	2588
  	AD-18965	uuGAuAcuGAccuGuAAAu	73	AUUuAcAGGUcAGuAUcAA	732	2598
  	AD-18966	GuGuAGAAcAcuAAuucAu	74	AUGAAUuAGUGUUCuAcAC	733	2907
  	AD-18967	AcuAuccAGuuGAuGGGcu	75	AGCCcAUcAACUGGAuAGU	734	2508
  	AD-18968	AAAucAGuAAGAGGuGuuA	76	uAAcACCUCUuACUGAUUU	735	3102
  	AD-18969	GcAGGuGGAucuAuuucAu	77	AUGAAAuAGAUCcACCUGC	736	3042
  	AD-18970	cuGGuGcuGAcuAuccAGu	78	ACUGGAuAGUcAGcACcAG	737	2499
  	AD-18971	GuGAAcuuGcucAGGAcAA	79	UUGUCCUGAGcAAGUUcAC	738	2124
  	AD-18972	ucAGuAAGAGGuGuuAuuu	80	AAAuAAcACCUCUuACUGA	739	3105
  	AD-18973	ccucuGuGAAcuuGcucAG	81	CUGAGcAAGUUcAcAGAGG	740	2119
  	AD-18974	uuGGcuGAAccAucAcAGA	82	UCUGUGAUGGUUcAGCcAA	741	641
  	AD-18975	ucAGcuGGccuGGuuuGAu	83	AUcAAACcAGGCcAGCUGA	742	2584
  	AD-18976	GuAGcuGcAGGGGuccucu	84	AGAGGACCCCUGcAGCuAC	743	2105
  	AD-18977	AGGAGcuAAAAuGGcAGuG	85	cACUGCcAUUUuAGCUCCU	744	1069
  	AD-18978	AuGGcuuGGAAuGAGAcuG	86	cAGUCUcAUUCcAAGCcAU	745	2330
  	AD-18979	uuGGAuAucGccAGGAuGA	87	UcAUCCUGGCGAuAUCcAA	746	2388
  	AD-18980	GGuucAGAAuuAAAcuuuu	88	AAAAGUUuAAUUCUGAACC	747	3224
  	AD-18981	GGGuAAAucAGuAAGAGGu	89	ACCUCUuACUGAUUuACCC	748	3098
  	AD-18982	AuAccAuuccAuuGuuuGu	90	AcAAAcAAUGGAAUGGuAU	749	2049
  	AD-18983	AcuGuuGGAuuGAuucGAA	91	UUCGAAUcAAUCcAAcAGU	750	1796
  	AD-18984	AAcuuGcucAGGAcAAGGA	92	UCCUUGUCCUGAGcAAGUU	751	2127
  	AD-18985	AuGcuuAAAAuAAGcAGGu	93	ACCUGCUuAUUUuAAGcAU	752	3029
  	AD-18986	GuuuGAuAcuGAccuGuAA	94	UuAcAGGUcAGuAUcAAAC	753	2596
  	AD-18987	AAuGGuucAGAAuuAAAcu	95	AGUUuAAUUCUGAACcAUU	754	3221
  	AD-18988	uAucccAAAGuuGuuGuAA	96	UuAcAAcAACUUUGGGAuA	755	3159
  	AD-18989	AucAGcuGGccuGGuuuGA	97	UcAAACcAGGCcAGCUGAU	756	2583
  	AD-18990	ccuGccAucuGuGcucuuc	98	GAAGAGcAcAGAUGGcAGG	757	1655
  	AD-18991	GcAGAAuAcAAAuGAuGuA	99	uAcAUcAUUUGuAUUCUGC	758	874
  	AD-18992	uAuGcuuAAAAuAAGcAGG	100	CCUGCUuAUUUuAAGcAuA	759	3028
  	AD-18993	AAuAAGcAGGuGGAucuAu	101	AuAGAUCcACCUGCUuAUU	760	3037
  	AD-18994	uGAuAuAAAuGuGGucAcc	102	GGUGACcAcAUUuAuAUcA	761	1504
  	AD-18995	GuAGGGuAAAucAGuAAGA	103	UCUuACUGAUUuACCCuAC	762	3095
  	AD-18996	uAucAAAcccuAGccuuGc	104	GcAAGGCuAGGGUUUGAuA	763	2703
  	AD-18997	ccuuuuAucccAAAGuuGu	105	AcAACUUUGGGAuAAAAGG	764	3154
  	AD-18998	GGuAGGGuAAAucAGuAAG	106	CUuACUGAUUuACCCuACC	765	3094
  	AD-18999	uGAuAcuGAccuGuAAAuc	107	GAUUuAcAGGUcAGuAUcA	766	2599
  	AD-19000	GGcuGAAccAucAcAGAuG	108	cAUCUGUGAUGGUUcAGCC	767	643
  	AD-19001	uGGAuAucGccAGGAuGAu	109	AUcAUCCUGGCGAuAUCcA	768	2389
  	AD-19002	ucuucGucAucuGAccAGc	110	GCUGGUcAGAUGACGAAGA	769	1669
  	AD-19003	uAGcuGcAGGGGuccucuG	111	cAGAGGACCCCUGcAGCuA	770	2106
  	AD-19004	uGuuGuAAccuGcuGuGAu	112	AUcAcAGcAGGUuAcAAcA	771	3170
  	AD-19005	AAucAGuAAGAGGuGuuAu	113	AuAAcACCUCUuACUGAUU	772	3103
  	AD-19006	uGGcuGAAccAucAcAGAu	114	AUCUGUGAUGGUUcAGCcA	773	642
  	AD-19007	GAAuuAAAcuuuuAAuucA	115	UGAAUuAAAAGUUuAAUUC	774	3230
  	AD-19008	AuGGuucAGAAuuAAAcuu	116	AAGUUuAAUUCUGAACcAU	775	3222
  	AD-19009	uGGuGuAGAAcAcuAAuuc	117	GAAUuAGUGUUCuAcACcA	776	2905
  	AD-19010	AuGGuGuAGAAcAcuAAuu	118	AAUuAGUGUUCuAcACcAU	777	2904
  	AD-19011	AuGAGGGcAuGcAGAuccc	119	GGGAUCUGcAUGCCCUcAU	778	579
  	AD-19012	GuuGuAAccuGcuGuGAuA	120	uAUcAcAGcAGGUuAcAAC	779	3171
  	AD-19042	GcuGAcuAuccAGuuGAuG	121	cAUcAACUGGAuAGUcAGC	780	2504
  	AD-19043	uAAGcAGGuGGAucuAuuu	122	AAAuAGAUCcACCUGCUuA	781	3039
  	AD-19044	uAAAAuAAGcAGGuGGAuc	123	GAUCcACCUGCUuAUUUuA	782	3034
  	AD-19045	GAuAuAAAuGuGGucAccu	124	AGGUGACcAcAUUuAuAUC	783	1505
  	AD-19046	AAGcAGAGuGcuGAAGGuG	125	cACCUUcAGcACUCUGCUU	784	1288
  	AD-19047	uGuGAAcuuGcucAGGAcA	126	UGUCCUGAGcAAGUUcAcA	785	2123
  	AD-19048	cAucccAcuAAuGuccAGc	127	GCUGGAcAUuAGUGGGAUG	786	620
  	AD-19049	cAAAGuuGuuGuAAccuGc	128	GcAGGUuAcAAcAACUUUG	787	3164
  	AD-19050	uAAAucAGuAAGAGGuGuu	129	AAcACCUCUuACUGAUUuA	788	3101
  	AD-19051	AAuGGcuuGGAAuGAGAcu	130	AGUCUcAUUCcAAGCcAUU	789	2329
  	AD-19052	GGGuccucuGuGAAcuuGc	131	GcAAGUUcAcAGAGGACCC	790	2115
  	AD-19053	GAGuAAcAAuAcAAAuGGA	132	UCcAUUUGuAUUGUuACUC	791	2627
  	AD-19054	uAAuGGuGuAGAAcAcuAA	133	UuAGUGUUCuAcACcAUuA	792	2902
  	AD-19055	GuGGAcAAuGGcuAcucAA	134	UUGAGuAGCcAUUGUCcAC	793	262
  	AD-19056	AAcuGucuuuGGAcucucA	135	UGAGAGUCcAAAGAcAGUU	794	1406
  	AD-19057	cccuGGuGcuGAcuAuccA	136	UGGAuAGUcAGcACcAGGG	795	2497
  	AD-19058	cAGGuGGAucuAuuucAuG	137	cAUGAAAuAGAUCcACCUG	796	3043
  	AD-19059	uGGccuGGuuuGAuAcuGA	138	UcAGuAUcAAACcAGGCcA	797	2589
  	AD-19060	AGcuGGccuGGuuuGAuAc	139	GuAUcAAACcAGGCcAGCU	798	2586
  	AD-19061	GccAucuGuGcucuucGuc	140	GACGAAGAGcAcAGAUGGC	799	1658
  	AD-19062	uAccAuuccAuuGuuuGuG	141	cAcAAAcAAUGGAAUGGuA	800	2050
  	AD-19063	cccuuGGAuAucGccAGGA	142	UCCUGGCGAuAUCcAAGGG	801	2385
  	AD-19064	AGGGAAGAcAucAcuGAGc	143	GCUcAGUGAUGUCUUCCCU	802	1637
  	AD-19065	GAAcuuGccAcAcGuGcAA	144	UUGcACGUGUGGcAAGUUC	803	707
  	AD-19066	uuuGAuAcuGAccuGuAAA	145	UUuAcAGGUcAGuAUcAAA	804	2597
  	AD-19067	ucccAAAGuuGuuGuAAcc	146	GGUuAcAAcAACUUUGGGA	805	3161
  	AD-19068	cAGAAuAcAAAuGAuGuAG	147	CuAcAUcAUUUGuAUUCUG	806	875
  	AD-19069	AGGuGGAucuAuuucAuGu	148	AcAUGAAAuAGAUCcACCU	807	3044
  	AD-19070	GcucAucccAcuAAuGucc	149	GGAcAUuAGUGGGAUGAGC	808	617
  	AD-19071	ccuGGuGcuGAcuAuccAG	150	CUGGAuAGUcAGcACcAGG	809	2498
  	AD-19072	uGGAAuccAuucuGGuGcc	151	GGcACcAGAAUGGAUUCcA	810	367
  	AD-19073	ccAGGAccucAuGGAuGGG	152	CCcAUCcAUGAGGUCCUGG	811	2545
  	AD-19074	AAccucAcuuGcAAuAAuu	153	AAUuAUUGcAAGUGAGGUU	812	1544
  	AD-19075	cAGuuGccuuuuAucccAA	154	UUGGGAuAAAAGGcAACUG	813	3148
  	AD-19076	GuAGAAcAcuAAuucAuAA	155	UuAUGAAUuAGUGUUCuAC	814	2909
  	AD-19077	cuAuccAGuuGAuGGGcuG	156	cAGCCcAUcAACUGGAuAG	815	2509
  	AD-19078	cAcuGGccucuGAuAAAGG	157	CCUUuAUcAGAGGCcAGUG	816	1775
  	AD-19079	AcuGucuuuGGAcucucAG	158	CUGAGAGUCcAAAGAcAGU	817	1407
  	AD-19080	ccAAuGGcuuGGAAuGAGA	159	UCUcAUUCcAAGCcAUUGG	818	2327
  	AD-19081	GcuuAAAAuAAGcAGGuGG	160	CcACCUGCUuAUUUuAAGC	819	3031
  	AD-19082	AucuGuGcucuucGucAuc	161	GAUGACGAAGAGcAcAGAU	820	1661
  	AD-19083	cccAAAGuuGuuGuAAccu	162	AGGUuAcAAcAACUUUGGG	821	3162
  	AD-19738	uAcccAGcGccGuAcGucc	163	GGACGuACGGCGCUGGGuA	822	1906
  	AD-19739	AcGcuAucAuGcGuucucc	164	GGAGAACGcAUGAuAGCGU	823	825
  	AD-19740	cAuGcAccuuuGcGuGAGc	165	GCUcACGcAAAGGUGcAUG	824	1838
  	AD-19741	GAAuGcAGuucGccuucAc	166	GUGAAGGCGAACUGcAUUC	825	1714
  	AD-19742	GGuGccAuuccAcGAcuAG	167	CuAGUCGUGGAAUGGcACC	826	1859
  	AD-19743	AAGcGGcuGuuAGucAcuG	168	cAGUGACuAAcAGCCGCUU	827	324
  	AD-19744	ucGAGcucAGAGGGuAcGA	169	UCGuACCCUCUGAGCUCGA	828	535
  	AD-19745	GAcAcGcuAucAuGcGuuc	170	GAACGcAUGAuAGCGUGUC	829	822
  	AD-19746	cGcuAucAuGcGuucuccu	171	AGGAGAACGcAUGAuAGCG	830	826
  	AD-19747	GuGucuGcuAuuGuAcGuA	172	uACGuAcAAuAGcAGAcAC	831	851
  	AD-19748	GucuGcucuAGuAAuAAGc	173	GCUuAUuACuAGAGcAGAC	832	1313
  	AD-19749	GuGccAuuccAcGAcuAGu	174	ACuAGUCGUGGAAUGGcAC	833	1860
  	AD-19750	AuGuucAcAAccGAAuuGu	175	AcAAUUCGGUUGUGAAcAU	834	2016
  	AD-19751	ccAcGAcuAGuucAGuuGc	176	GcAACUGAACuAGUCGUGG	835	1868
  	AD-19752	cAcGAcuAGuucAGuuGcu	177	AGcAACUGAACuAGUCGUG	836	1869
  	AD-19753	AGuucAGuuGcuuGuucGu	178	ACGAAcAAGcAACUGAACU	837	1876
  	AD-19754	cccAGcGccGuAcGuccAu	179	AUGGACGuACGGCGCUGGG	838	1908
  	AD-19755	GAGuuAcuucAcucuAGGA	180	UCCuAGAGUGAAGuAACUC	839	2192
  	AD-19756	AcAGuAuGcAAuGAcucGA	181	UCGAGUcAUUGcAuACUGU	840	520
  	AD-19757	uAuGcAAuGAcucGAGcuc	182	GAGCUCGAGUcAUUGcAuA	841	524
  	AD-19758	cccAcuAAuGuccAGcGuu	183	AACGCUGGAcAUuAGUGGG	842	623
  	AD-19759	GAccuuGcAuAAccuuucc	184	GGAAAGGUuAUGcAAGGUC	843	916
  	AD-19760	uAuuAcGAcAGAcuGccuu	185	AAGGcAGUCUGUCGuAAuA	844	1153
  	AD-19761	AucuGAccAGccGAcAccA	186	UGGUGUCGGCUGGUcAGAU	845	1677
  	AD-19762	cAuuccAcGAcuAGuucAG	187	CUGAACuAGUCGUGGAAUG	846	1864
  	AD-19763	GuuuuGAAAAuccAGcGuG	188	cACGCUGGAUUUUcAAAAC	847	246
  	AD-19765	GcGuuuGGcuGAAccAucA	189	UGAUGGUUcAGCcAAACGC	848	637
  	AD-19766	AcAcGcuAucAuGcGuucu	190	AGAACGcAUGAuAGCGUGU	849	823
  	AD-19767	uAuGccAuuAcAAcucucc	191	GGAGAGUUGuAAUGGcAuA	850	1028
  	AD-19768	ucuGcucuAGuAAuAAGcc	192	GGCUuAUuACuAGAGcAGA	851	1314
  	AD-20124	cGGGAuGuucAcAAccGAA	193	UUCGGUUGUGAAcAUCCCG	852	2012
  	AD-25889	AcAAuAcAAAuGGAuuuuG	194	cAAAAUCcAUUUGuAUUGU	853	2632
  	AD-25890	AcAAAuGGAuuuuGGGAGu	195	ACUCCcAAAAUCcAUUUGU	854	2637
  	AD-25891	uuGGGAGuGAcucAAGAAG	196	CUUCUUGAGUcACUCCcAA	855	2648
  	AD-25892	uGGGAGuGAcucAAGAAGu	197	ACUUCUUGAGUcACUCCcA	856	2649
  	AD-25893	GAAGuGAAGAAuGcAcAAG	198	CUUGUGcAUUCUUcACUUC	857	2663
  	AD-25894	AAGuGAAGAAuGcAcAAGA	199	UCUUGUGcAUUCUUcACUU	858	2664
  	AD-25895	GAuGGAAuuuAucAAAccc	200	GGGUUUGAuAAAUUCcAUC	859	2694
  	AD-25896	AuGGAAuuuAucAAAcccu	201	AGGGUUUGAuAAAUUCcAU	860	2695
  	AD-25897	GGAAuuuAucAAAcccuAG	202	CuAGGGUUUGAuAAAUUCC	861	2697
  	AD-25898	GAAuuuAucAAAcccuAGc	203	GCuAGGGUUUGAuAAAUUC	862	2698
  	AD-25899	AAuuuAucAAAcccuAGcc	204	GGCuAGGGUUUGAuAAAUU	863	2699
  	AD-25900	GAAuAucuGuAAuGGuAcu	205	AGuACcAUuAcAGAuAUUC	864	2751
  	AD-25901	AAuAucuGuAAuGGuAcuG	206	cAGuACcAUuAcAGAuAUU	865	2752
  	AD-25902	AuAucuGuAAuGGuAcuGA	207	UcAGuACcAUuAcAGAuAU	866	2753
  	AD-25903	uuuuAAGucucucGuAGuG	208	cACuACGAGAGACUuAAAA	867	2832
  	AD-25904	uuuAAGucucucGuAGuGu	209	AcACuACGAGAGACUuAAA	868	2833
  	AD-25905	AGucucucGuAGuGuuAAG	210	CUuAAcACuACGAGAGACU	869	2837
  	AD-25906	ucGuAGuGuuAAGuuAuAG	211	CuAuAACUuAAcACuACGA	870	2843
  	AD-25907	cGuAGuGuuAAGuuAuAGu	212	ACuAuAACUuAAcACuACG	871	2844
  	AD-25908	GuAGuGuuAAGuuAuAGuG	213	cACuAuAACUuAAcACuAC	872	2845
  	AD-25909	uAGuGuuAAGuuAuAGuGA	214	UcACuAuAACUuAAcACuA	873	2846
  	AD-25910	uAGuGAAuAcuGcuAcAGc	215	GCUGuAGcAGuAUUcACuA	874	2859
  	AD-25911	AAcAcuAAuucAuAAucAc	216	GUGAUuAUGAAUuAGUGUU	875	2913
  	AD-25912	AcAcuAAuucAuAAucAcu	217	AGUGAUuAUGAAUuAGUGU	876	2914
  	AD-25913	uAAuuGuAAucuGAAuAAA	218	UUuAUUcAGAUuAcAAUuA	877	2938
  	AD-25914	AuuGuAAucuGAAuAAAGu	219	ACUUuAUUcAGAUuAcAAU	878	2940
  	AD-25915	uuGuAAucuGAAuAAAGuG	220	cACUUuAUUcAGAUuAcAA	879	2941
  	AD-25916	uGuAAucuGAAuAAAGuGu	221	AcACUUuAUUcAGAUuAcA	880	2942
  	AD-25917	GAcAAAuAGAAAAuGGucc	222	GGACcAUUUUCuAUUUGUC	881	2991
  	AD-25918	AcAAAuAGAAAAuGGuccA	223	UGGACcAUUUUCuAUUUGU	882	2992
  	AD-25919	uAGAAAAuGGuccAAuuAG	224	CuAAUUGGACcAUUUUCuA	883	2997
  	AD-25920	AGAAAAuGGuccAAuuAGu	225	ACuAAUUGGACcAUUUUCU	884	2998
  	AD-25921	uAuuuGGGAuAuGuAuGGG	226	CCcAuAcAuAUCCcAAAuA	885	3077
  	AD-25922	AuuuGGGAuAuGuAuGGGu	227	ACCcAuAcAuAUCCcAAAU	886	3078
  	AD-25923	uuGGGAuAuGuAuGGGuAG	228	CuACCcAuAcAuAUCCcAA	887	3080
  	AD-25924	GGAuAuGuAuGGGuAGGGu	229	ACCCuACCcAuAcAuAUCC	888	3083
  	AD-25925	AAGAGGuGuuAuuuGGAAc	230	GUUCcAAAuAAcACCUCUU	889	3110
  	AD-25926	AGAGGuGuuAuuuGGAAcc	231	GGUUCcAAAuAAcACCUCU	890	3111
  	AD-25927	GAGGuGuuAuuuGGAAccu	232	AGGUUCcAAAuAAcACCUC	891	3112
  	AD-25928	uGGAAccuuGuuuuGGAcA	233	UGUCcAAAAcAAGGUUCcA	892	3123
  	AD-25929	GGAAccuuGuuuuGGAcAG	234	CUGUCcAAAAcAAGGUUCC	893	3124
  	AD-25930	GAAccuuGuuuuGGAcAGu	235	ACUGUCcAAAAcAAGGUUC	894	3125
  	AD-25931	GuuuuGGAcAGuuuAccAG	236	CUGGuAAACUGUCcAAAAC	895	3132
  	AD-25932	uuuuGGAcAGuuuAccAGu	237	ACUGGuAAACUGUCcAAAA	896	3133
  	AD-25933	uuGGAcAGuuuAccAGuuG	238	cAACUGGuAAACUGUCcAA	897	3135
  	AD-25934	GuuGuuGuAAccuGcuGuG	239	cAcAGcAGGUuAcAAcAAC	898	3168
  	AD-25935	uuGuuGuAAccuGcuGuGA	240	UcAcAGcAGGUuAcAAcAA	899	3169
  	AD-25936	uuGuAAccuGcuGuGAuAc	241	GuAUcAcAGcAGGUuAcAA	900	3172
  	AD-25937	AuGcuucAAGAGAAAAuGc	242	GcAUUUUCUCUUGAAGcAU	901	3192
  	AD-25938	AGuGAAGAAuGcAcAAGAA	243	UUCUUGUGcAUUCUUcACU	902	2665
  	AD-25939	AAuGGAucAcAAGAuGGAA	244	UUCcAUCUUGUGAUCcAUU	903	2682
  	AD-25940	AuGGAucAcAAGAuGGAAu	245	AUUCcAUCUUGUGAUCcAU	904	2683
  	AD-25941	uGGAucAcAAGAuGGAAuu	246	AAUUCcAUCUUGUGAUCcA	905	2684
  	AD-25942	GGAucAcAAGAuGGAAuuu	247	AAAUUCcAUCUUGUGAUCC	906	2685
  	AD-25943	GAucAcAAGAuGGAAuuuA	248	uAAAUUCcAUCUUGUGAUC	907	2686
  	AD-25944	AucAcAAGAuGGAAuuuAu	249	AuAAAUUCcAUCUUGUGAU	908	2687
  	AD-25945	uGGAAuuuAucAAAcccuA	250	uAGGGUUUGAuAAAUUCcA	909	2696
  	AD-25946	AcccuAGccuuGcuuGuuA	251	uAAcAAGcAAGGCuAGGGU	910	2709
  	AD-25947	cccuAGccuuGcuuGuuAA	252	UuAAcAAGcAAGGCuAGGG	911	2710
  	AD-25948	ccuAGccuuGcuuGuuAAA	253	UUuAAcAAGcAAGGCuAGG	912	2711
  	AD-25949	cuAGccuuGcuuGuuAAAu	254	AUUuAAcAAGcAAGGCuAG	913	2712
  	AD-25950	uAGccuuGcuuGuuAAAuu	255	AAUUuAAcAAGcAAGGCuA	914	2713
  	AD-25951	AGccuuGcuuGuuAAAuuu	256	AAAUUuAAcAAGcAAGGCU	915	2714
  	AD-25952	uuAAGucucucGuAGuGuu	257	AAcACuACGAGAGACUuAA	916	2834
  	AD-25953	uAAGucucucGuAGuGuuA	258	uAAcACuACGAGAGACUuA	917	2835
  	AD-25954	AAGucucucGuAGuGuuAA	259	UuAAcACuACGAGAGACUU	918	2836
  	AD-25955	cucGuAGuGuuAAGuuAuA	260	uAuAACUuAAcACuACGAG	919	2842
  	AD-25956	AGuGuuAAGuuAuAGuGAA	261	UUcACuAuAACUuAAcACU	920	2847
  	AD-25957	GuGuuAAGuuAuAGuGAAu	262	AUUcACuAuAACUuAAcAC	921	2848
  	AD-25958	cuAcAGcAAuuucuAAuuu	263	AAAUuAGAAAUUGCUGuAG	922	2871
  	AD-25959	cAAAuAGAAAAuGGuccAA	264	UUGGACcAUUUUCuAUUUG	923	2993
  	AD-25960	AuAGAAAAuGGuccAAuuA	265	uAAUUGGACcAUUUUCuAU	924	2996
  	AD-25961	uuuGGGAuAuGuAuGGGuA	266	uACCcAuAcAuAUCCcAAA	925	3079
  	AD-25962	GAuAuGuAuGGGuAGGGuA	267	uACCCuACCcAuAcAuAUC	926	3084
  	AD-25963	uGGGuAGGGuAAAucAGuA	268	uACUGAUUuACCCuACCcA	927	3092
  	AD-25964	uAAGAGGuGuuAuuuGGAA	269	UUCcAAAuAAcACCUCUuA	928	3109
  	AD-26017	uGccuuuuAucccAAAGuu	270	AACUUUGGGAuAAAAGGcA	929	3152
  	AD-26018	uGuuGuAAccuGcuGuGAu	271	AUcAcAGcAGGUuAcAAcA	930	3170
  	AD-26019	GuuGuAAccuGcuGuGAuA	272	uAUcAcAGcAGGUuAcAAC	931	3171
  	AD-26020	cAAGAGAAAAuGcGGuuAu	273	AuAACCGcAUUUUCUCUUG	932	3198
  	AD-26021	AAGAGAAAAuGcGGuuAuA	274	uAuAACCGcAUUUUCUCUU	933	3199
  	AD-26022	ccuGuuccccuGAGGGuAu	275	AuACCCUcAGGGGAAcAGG	934	207
  	AD-26023	cuGuuccccuGAGGGuAuu	276	AAuACCCUcAGGGGAAcAG	935	208
  	AD-26024	ccuGAGGGuAuuuGAAGuA	277	uACUUcAAAuACCCUcAGG	936	215
  	AD-26025	cuGAGGGuAuuuGAAGuAu	278	AuACUUcAAAuACCCUcAG	937	216
  	AD-26026	uGAGGGuAuuuGAAGuAuA	279	uAuACUUcAAAuACCCUcA	938	217
  	AD-26027	GGuAuuuGAAGuAuAccAu	280	AUGGuAuACUUcAAAuACC	939	221
  	AD-26028	GuAuuuGAAGuAuAccAuA	281	uAUGGuAuACUUcAAAuAC	940	222
  	AD-26029	uuuGAAGuAuAccAuAcAA	282	UUGuAUGGuAuACUUcAAA	941	225
  	AD-26030	AGuAuAccAuAcAAcuGuu	283	AAcAGUUGuAUGGuAuACU	942	230
  	AD-26031	GuAuAccAuAcAAcuGuuu	284	AAAcAGUUGuAUGGuAuAC	943	231
  	AD-26032	uAuAccAuAcAAcuGuuuu	285	AAAAcAGUUGuAUGGuAuA	944	232
  	AD-26033	AccAuAcAAcuGuuuuGAA	286	UUcAAAAcAGUUGuAUGGU	945	235
  	AD-26034	ccAuAcAAcuGuuuuGAAA	287	UUUcAAAAcAGUUGuAUGG	946	236
  	AD-26035	GAAAAuccAGcGuGGAcAA	288	UUGUCcACGCUGGAUUUUC	947	251
  	AD-26036	AAAAuccAGcGuGGAcAAu	289	AUUGUCcACGCUGGAUUUU	948	252
  	AD-26037	ccAGcGuGGAcAAuGGcuA	290	uAGCcAUUGUCcACGCUGG	949	257
  	AD-26038	GuGGAcAAuGGcuAcucAA	291	UUGAGuAGCcAUUGUCcAC	950	262
  	AD-26039	AAuGGcuAcucAAGcuGAu	292	AUcAGCUUGAGuAGCcAUU	951	268
  	AD-26040	AuGGcuAcucAAGcuGAuu	293	AAUcAGCUUGAGuAGCcAU	952	269
  	AD-26041	uGGcuAcucAAGcuGAuuu	294	AAAUcAGCUUGAGuAGCcA	953	270
  	AD-26042	cuAcucAAGcuGAuuuGAu	295	AUcAAAUcAGCUUGAGuAG	954	273
  	AD-26043	AuuuGAuGGAGuuGGAcAu	296	AUGUCcAACUCcAUcAAAU	955	285
  	AD-26044	uGGAGuuGGAcAuGGccAu	297	AUGGCcAUGUCcAACUCcA	956	291
  	AD-26045	GuuGGAcAuGGccAuGGAA	298	UUCcAUGGCcAUGUCcAAC	957	295
  	AD-26046	GccAuGGAAccAGAcAGAA	299	UUCUGUCUGGUUCcAUGGC	958	305
  	AD-26047	cAuGGAAccAGAcAGAAAA	300	UUUUCUGUCUGGUUCcAUG	959	307
  	AD-26048	GGAGGcGGAGAcGGAGGAA	301	UUCCUCCGUCUCCGCCUCC	960	111
  	AD-26049	AGAcAGAAAAGcGGcuGuu	302	AAcAGCCGCUUUUCUGUCU	961	316
  	AD-26050	GAcAGAAAAGcGGcuGuuA	303	uAAcAGCCGCUUUUCUGUC	962	317
  	AD-26051	uGuuAGucAcuGGcAGcAA	304	UUGCUGCcAGUGACuAAcA	963	331
  	AD-26052	cAcuGGcAGcAAcAGucuu	305	AAGACUGUUGCUGCcAGUG	964	338
  	AD-26053	AcuGGcAGcAAcAGucuuA	306	uAAGACUGUUGCUGCcAGU	965	339
  	AD-26054	ucuuAccuGGAcucuGGAA	307	UUCcAGAGUCcAGGuAAGA	966	353
  	AD-26055	cuuAccuGGAcucuGGAAu	308	AUUCcAGAGUCcAGGuAAG	967	354
  	AD-26056	ccuGGAcucuGGAAuccAu	309	AUGGAUUCcAGAGUCcAGG	968	358
  	AD-26057	GGcuAGuGGuGGAccccAA	310	UUGGGGUCcACcACuAGCC	969	1216
  	AD-26058	GccAcuAccAcAGcuccuu	311	AAGGAGCUGUGGuAGUGGC	970	383
  	AD-26059	uccuucucuGAGuGGuAAA	312	UUuACcACUcAGAGAAGGA	971	397
  	AD-26060	cucuGAGuGGuAAAGGcAA	313	UUGCCUUuACcACUcAGAG	972	402
  	AD-26061	uAAAGGcAAuccuGAGGAA	314	UUCCUcAGGAUUGCCUUuA	973	412
  	AD-26062	cAAuccuGAGGAAGAGGAu	315	AUCCUCUUCCUcAGGAUUG	974	418
  	AD-26063	uGAGGAAGAGGAuGuGGAu	316	AUCcAcAUCCUCUUCCUcA	975	424
  	AD-26064	AuAccucccAAGuccuGuA	317	uAcAGGACUUGGGAGGuAU	976	441
  	AD-26065	uAccucccAAGuccuGuAu	318	AuAcAGGACUUGGGAGGuA	977	442
  	AD-26066	AGuccuGuAuGAGuGGGAA	319	UUCCcACUcAuAcAGGACU	978	451
  	AD-26067	uAuGAGuGGGAAcAGGGAu	320	AUCCCUGUUCCcACUcAuA	979	458
  	AD-26068	cAAGcuuuAGuAAAuAuAA	321	UuAuAUUuACuAAAGCUUG	980	1232
  	AD-26069	AAGcuuuAGuAAAuAuAAu	322	AUuAuAUUuACuAAAGCUU	981	1233
  	AD-26070	uGAGuGGGAACAGGGAuuu	323	AAAUCCCUGUUCCcACUcA	982	460
  	AD-26071	GAGuGGGAACAGGGAuuuu	324	AAAAUCCCUGUUCCcACUC	983	461
  	AD-26072	AGGGAuuuucucAGuccuu	325	AAGGACUGAGAAAAUCCCU	984	471
  	AD-26073	uucucAGuccuucAcucAA	326	UUGAGUGAAGGACUGAGAA	985	478
  	AD-26074	ucAGuccuucAcucAAGAA	327	UUCUUGAGUGAAGGACUGA	986	481
  	AD-26075	cuucAcucAAGAAcAAGuA	328	uACUUGUUCUUGAGUGAAG	987	487
  	AD-26076	ucAAGAAcAAGuAGcuGAu	329	AUcAGCuACUUGUUCUUGA	988	493
  	AD-26077	cuGAuAuuGAuGGAcAGuA	330	uACUGUCcAUcAAuAUcAG	989	507
  	AD-26078	AuuGAuGGAcAGuAuGcAA	331	UUGcAuACUGUCcAUcAAU	990	512
  	AD-26079	GAcucGAGcucAGAGGGuA	332	uACCCUCUGAGCUCGAGUC	991	532
  	AD-26080	cAGAGGGuAcGAGcuGcuA	333	uAGcAGCUCGuACCCUCUG	992	542
  	AD-26081	AGAGGGuAcGAGcuGcuAu	334	AuAGcAGCUCGuACCCUCU	993	543
  	AD-26082	GGGuAcGAGcuGcuAuGuu	335	AAcAuAGcAGCUCGuACCC	994	546
  	AD-26083	cuAuGuucccuGAGAcAuu	336	AAUGUCUcAGGGAAcAuAG	995	558
  	AD-26084	uAuGuucccuGAGAcAuuA	337	uAAUGUCUcAGGGAAcAuA	996	559
  	AD-26085	GuucccuGAGAcAuuAGAu	338	AUCuAAUGUCUcAGGGAAC	997	562
  	AD-26086	uAGAuGAGGGcAuGcAGAu	339	AUCUGcAUGCCCUcAUCuA	998	576
  	AD-26087	GAGGGcAuGcAGAucccAu	340	AUGGGAUCUGcAUGCCCUC	999	581
  	AD-26088	GGcAuGcAGAucccAucuA	341	uAGAUGGGAUCUGcAUGCC	1000	584
  	AD-26089	AGAucccAucuAcAcAGuu	342	AACUGUGuAGAUGGGAUCU	1001	591
  	AD-26090	cccAucuAcAcAGuuuGAu	343	AUcAAACUGUGuAGAUGGG	1002	595
  	AD-26091	AcAGuuuGAuGcuGcucAu	344	AUGAGcAGcAUcAAACUGU	1003	604
  	AD-26092	GAuGcuGcucAucccAcuA	345	uAGUGGGAUGAGcAGcAUC	1004	611
  	AD-26093	AuGcuGcucAucccAcuAA	346	UuAGUGGGAUGAGcAGcAU	1005	612
  	AD-26094	uGcuGcucAucccAcuAAu	347	AUuAGUGGGAUGAGcAGcA	1006	613
  	AD-26095	cccAcuAAuGuccAGcGuu	348	AACGCUGGAcAUuAGUGGG	1007	623
  	AD-26096	cAGcGuuuGGcuGAAccAu	349	AUGGUUcAGCcAAACGCUG	1008	635
  	AD-26097	uGGcuGAAccAucAcAGAu	350	AUCUGUGAUGGUUcAGCcA	1009	642
  	AD-26098	AAccAucAcAGAuGcuGAA	351	UUcAGcAUCUGUGAUGGUU	1010	648
  	AD-26099	AccAucAcAGAuGcuGAAA	352	UUUcAGcAUCUGUGAUGGU	1011	649
  	AD-26100	AucAcAGAuGcuGAAAcAu	353	AUGUUUcAGcAUCUGUGAU	1012	652
  	AD-26101	GAuGcuGAAAcAuGcAGuu	354	AACUGcAUGUUUcAGcAUC	1013	658
  	AD-26102	cuGAAAcAuGcAGuuGuAA	355	UuAcAACUGcAUGUUUcAG	1014	662
  	AD-26103	AAcAuGcAGuuGuAAAcuu	356	AAGUUuAcAACUGcAUGUU	1015	666
  	AD-26104	AuGcAGuuGuAAAcuuGAu	357	AUcAAGUUuAcAACUGcAU	1016	669
  	AD-26105	uGcAGuuGuAAAcuuGAuu	358	AAUcAAGUUuAcAACUGcA	1017	670
  	AD-26106	cAGuuGuAAAcuuGAuuAA	359	UuAAUcAAGUUuAcAACUG	1018	672
  	AD-26107	cuuGAuuAAcuAucAAGAu	360	AUCUUGAuAGUuAAUcAAG	1019	682
  	AD-26108	GAuuAAcuAucAAGAuGAu	361	AUcAUCUUGAuAGUuAAUC	1020	685
  	AD-26109	cuAucAAGAuGAuGcAGAA	362	UUCUGcAUcAUCUUGAuAG	1021	691
  	AD-26110	GAAcuuGccAcAcGuGcAA	363	UUGcACGUGUGGcAAGUUC	1022	707
  	AD-26111	AAcuuGccAcAcGuGcAAu	364	AUUGcACGUGUGGcAAGUU	1023	708
  	AD-26112	cAcAcGuGcAAucccuGAA	365	UUcAGGGAUUGcACGUGUG	1024	715
  	AD-26123	GcAAucccuGAAcuGAcAA	366	UUGUcAGUUcAGGGAUUGC	1025	722
  	AD-26124	cAAucccuGAAcuGAcAAA	367	UUUGUcAGUUcAGGGAUUG	1026	723
  	AD-26125	AAucccuGAAcuGAcAAAA	368	UUUUGUcAGUUcAGGGAUU	1027	724
  	AD-26126	uGAAcuGAcAAAAcuGcuA	369	uAGcAGUUUUGUcAGUUcA	1028	730
  	AD-26127	GAAcuGAcAAAAcuGcuAA	370	UuAGcAGUUUUGUcAGUUC	1029	731
  	AD-26128	AAcuGAcAAAAcuGcuAAA	371	UUuAGcAGUUUUGUcAGUU	1030	732
  	AD-26129	AcuGAcAAAAcuGcuAAAu	372	AUUuAGcAGUUUUGUcAGU	1031	733
  	AD-26130	GAGGAccAGGuGGuGGuuA	373	uAACcACcACCUGGUCCUC	1032	755
  	AD-26131	AGGAccAGGuGGuGGuuAA	374	UuAACcACcACCUGGUCCU	1033	756
  	AD-26132	GGAccAGGuGGuGGuuAAu	375	AUuAACcACcACCUGGUCC	1034	757
  	AD-26133	GAccAGGuGGuGGuuAAuA	376	uAUuAACcACcACCUGGUC	1035	758
  	AD-26134	ucAcuuGcAAuAAuuAuAA	377	UuAuAAUuAUUGcAAGUGA	1036	1548
  	AD-26135	cuuGcAAuAAuuAuAAGAA	378	UUCUuAuAAUuAUUGcAAG	1037	1551
  	AD-26136	AccAGGuGGuGGuuAAuAA	379	UuAUuAACcACcACCUGGU	1038	759
  	AD-26137	GGcuGcAGuuAuGGuccAu	380	AUGGACcAuAACUGcAGCC	1039	778
  	AD-26138	GuuAuGGuccAucAGcuuu	381	AAAGCUGAUGGACcAuAAC	1040	785
  	AD-26139	AuGGuccAucAGcuuucuA	382	uAGAAAGCUGAUGGACcAU	1041	788
  	AD-26140	uGGuccAucAGcuuucuAA	383	UuAGAAAGCUGAUGGACcA	1042	789
  	AD-26141	ucGGGcuGGuGAcAGGGAA	384	UUCCCUGUcACcAGCCCGA	1043	1624
  	AD-26142	GGuccAucAGcuuucuAAA	385	UUuAGAAAGCUGAUGGACC	1044	790
  	AD-26143	GuccAucAGcuuucuAAAA	386	UUUuAGAAAGCUGAUGGAC	1045	791
  	AD-26144	GAAGcuuccAGAcAcGcuA	387	uAGCGUGUCUGGAAGCUUC	1046	812
  	AD-26145	AAGcuuccAGAcAcGcuAu	388	AuAGCGUGUCUGGAAGCUU	1047	813
  	AD-26146	cuuccAGAcAcGcuAucAu	389	AUGAuAGCGUGUCUGGAAG	1048	816
  	AD-26147	AGAcAcGcuAucAuGcGuu	390	AACGcAUGAuAGCGUGUCU	1049	821
  	AD-26148	ucAuGcGuucuccucAGAu	391	AUCUGAGGAGAACGcAUGA	1050	831
  	AD-26149	ccucAGAuGGuGucuGcuA	392	uAGcAGAcACcAUCUGAGG	1051	842
  	AD-26150	cucAGAuGGuGucuGcuAu	393	AuAGcAGAcACcAUCUGAG	1052	843
  	AD-26151	GuGucuGcuAuuGuAcGuA	394	uACGuAcAAuAGcAGAcAC	1053	851
  	AD-26152	cuGcuAuuGuAcGuAccAu	395	AUGGuACGuAcAAuAGcAG	1054	855
  	AD-26153	uuGuAcGuAccAuGcAGAA	396	UUCUGcAUGGuACGuAcAA	1055	861
  	AD-26154	uGuAcGuAccAuGcAGAAu	397	AUUCUGcAUGGuACGuAcA	1056	862
  	AD-26155	cGuAccAuGcAGAAuAcAA	398	UUGuAUUCUGcAUGGuACG	1057	866
  	AD-26156	cAuGcAGAAuAcAAAuGAu	399	AUcAUUUGuAUUCUGcAUG	1058	871
  	AD-26157	GcAGAAuAcAAAuGAuGuA	400	uAcAUcAUUUGuAUUCUGC	1059	874
  	AD-26158	GAAuAcAAAuGAuGuAGAA	401	UUCuAcAUcAUUUGuAUUC	1060	877
  	AD-26159	GAuGuAGAAAcAGcucGuu	402	AACGAGCUGUUUCuAcAUC	1061	887
  	AD-26160	GuuGuAccGcuGGGAccuu	403	AAGGUCCcAGCGGuAcAAC	1062	903
  	AD-26161	uAccGcuGGGAccuuGcAu	404	AUGcAAGGUCCcAGCGGuA	1063	907
  	AD-26162	ccGcuGGGAccuuGcAuAA	405	UuAUGcAAGGUCCcAGCGG	1064	909
  	AD-26163	uGGGAccuuGcAuAAccuu	406	AAGGUuAUGcAAGGUCCcA	1065	913
  	AD-26164	GGGAccuuGcAuAAccuuu	407	AAAGGUuAUGcAAGGUCCC	1066	914
  	AD-26165	cuuGcAuAAccuuucccAu	408	AUGGGAAAGGUuAUGcAAG	1067	919
  	AD-26166	ucuuuAAGucuGGAGGcAu	409	AUGCCUCcAGACUuAAAGA	1068	960
  	AD-26167	GcAuuccuGcccuGGuGAA	410	UUcACcAGGGcAGGAAUGC	1069	975
  	AD-26168	cAuuccuGcccuGGuGAAA	411	UUUcACcAGGGcAGGAAUG	1070	976
  	AD-26169	AuuccuGcccuGGuGAAAA	412	UUUUcACcAGGGcAGGAAU	1071	977
  	AD-26170	uuccuGcccuGGuGAAAAu	413	AUUUUcACcAGGGcAGGAA	1072	978
  	AD-26171	uGcccuGGuGAAAAuGcuu	414	AAGcAUUUUcACcAGGGcA	1073	982
  	AD-26172	cuGGuGAAAAuGcuuGGuu	415	AACcAAGcAUUUUcACcAG	1074	986
  	AD-26173	GcuuGGuucAccAGuGGAu	416	AUCcACUGGUGAACcAAGC	1075	997
  	AD-26174	cuuGGuucAccAGuGGAuu	417	AAUCcACUGGUGAACcAAG	1076	998
  	AD-26175	uGcGuGAGcAGGGuGccAu	418	AUGGcACCCUGCUcACGcA	1077	1848
  	AD-26176	GcGuGAGcAGGGuGccAuu	419	AAUGGcACCCUGCUcACGC	1078	1849
  	AD-26177	cAccAGuGGAuucuGuGuu	420	AAcAcAGAAUCcACUGGUG	1079	1005
  	AD-26178	cAGuGGAuucuGuGuuGuu	421	AAcAAcAcAGAAUCcACUG	1080	1008
  	AD-26179	AGuGGAuucuGuGuuGuuu	422	AAAcAAcAcAGAAUCcACU	1081	1009
  	AD-26180	GuGGAuucuGuGuuGuuuu	423	AAAAcAAcAcAGAAUCcAC	1082	1010
  	AD-26181	uGGAuucuGuGuuGuuuuA	424	uAAAAcAAcAcAGAAUCcA	1083	1011
  	AD-26182	GGAuucuGuGuuGuuuuAu	425	AuAAAAcAAcAcAGAAUCC	1084	1012
  	AD-26183	uGuGuuGuuuuAuGccAuu	426	AAUGGcAuAAAAcAAcAcA	1085	1018
  	AD-26184	GGGuGGGAcAcAGcAGcAA	427	UUGCUGCUGUGUCCcACCC	1086	1927
  	AD-26185	GuGuuGuuuuAuGccAuuA	428	uAAUGGcAuAAAAcAAcAC	1087	1019
  	AD-26186	uuGuuuuAuGccAuuAcAA	6495	UUGuAAUGGcAuAAAAcAA	1088	1022
  	AD-26187	ccAuuAcAAcucuccAcAA	6496	UUGUGGAGAGUUGuAAUGG	1089	1032
  	AD-26188	uAcAAcucuccAcAAccuu	431	AAGGUUGUGGAGAGUUGuA	1090	1036
  	AD-26189	AcAAcucuccAcAAccuuu	432	AAAGGUUGUGGAGAGUUGU	1091	1037
  	AD-26190	cAAcucuccAcAAccuuuu	433	AAAAGGUUGUGGAGAGUUG	1092	1038
  	AD-26191	AAcucuccAcAAccuuuuA	434	uAAAAGGUUGUGGAGAGUU	1093	1039
  	AD-26192	AcucuccAcAAccuuuuAu	435	AuAAAAGGUUGUGGAGAGU	1094	1040
  	AD-26193	cucuccAcAAccuuuuAuu	436	AAuAAAAGGUUGUGGAGAG	1095	1041
  	AD-26194	ucuccAcAAccuuuuAuuA	437	uAAuAAAAGGUUGUGGAGA	1096	1042
  	AD-26195	cAAccuuuuAuuAcAucAA	438	UUGAUGuAAuAAAAGGUUG	1097	1048
  	AD-26196	ccuuuuAuuAcAucAAGAA	439	UUCUUGAUGuAAuAAAAGG	1098	1051
  	AD-26197	uuAcAucAAGAAGGAGcuA	440	uAGCUCCUUCUUGAUGuAA	1099	1058
  	AD-26198	uAcAucAAGAAGGAGcuAA	441	UuAGCUCCUUCUUGAUGuA	1100	1059
  	AD-26199	cAucAAGAAGGAGcuAAAA	442	UUUuAGCUCCUUCUUGAUG	1101	1061
  	AD-26200	AucAAGAAGGAGcuAAAAu	443	AUUUuAGCUCCUUCUUGAU	1102	1062
  	AD-26201	GcuAAAAuGGcAGuGcGuu	444	AACGcACUGCcAUUUuAGC	1103	1073
  	AD-26202	uAAAAuGGcAGuGcGuuuA	445	uAAACGcACUGCcAUUUuA	1104	1075
  	AD-26203	AAAuGGuuGccuuGcucAA	446	UUGAGcAAGGcAACcAUUU	1105	1110
  	AD-26204	GccuGuuccccuGAGGGuA	447	uACCCUcAGGGGAAcAGGC	1106	206
  	AD-26205	uGGuuGccuuGcucAAcAA	448	UUGUUGAGcAAGGcAACcA	1107	1113
  	AD-26206	GGuuGccuuGcucAAcAAA	449	UUUGUUGAGcAAGGcAACC	1108	1114
  	AD-26207	GuuGccuuGcucAAcAAAA	450	UUUUGUUGAGcAAGGcAAC	1109	1115
  	AD-26208	GccuuGcucAAcAAAAcAA	451	UUGUUUUGUUGAGcAAGGC	1110	1118
  	AD-26209	ccuuGcucAAcAAAAcAAA	452	UUUGUUUUGUUGAGcAAGG	1111	1119
  	AD-26210	GuuAAAuucuuGGcuAuuA	453	uAAuAGCcAAGAAUUuAAC	1112	1139
  	AD-26211	uAuuAcGAcAGAcuGccuu	454	AAGGcAGUCUGUCGuAAuA	1113	1153
  	AD-26212	AuGGcAAccAAGAAAGcAA	455	UUGCUUUCUUGGUUGCcAU	1114	1185
  	AD-26213	AGuGGuGGAccccAAGcuu	456	AAGCUUGGGGUCcACcACU	1115	1220
  	AD-26214	GuGGuGGAccccAAGcuuu	457	AAAGCUUGGGGUCcACcAC	1116	1221
  	AD-26215	uGGuGGAccccAAGcuuuA	458	uAAAGCUUGGGGUCcACcA	1117	1222
  	AD-26216	uGGAccccAAGcuuuAGuA	459	uACuAAAGCUUGGGGUCcA	1118	1225
  	AD-26217	GGAccccAAGcuuuAGuAA	460	UuACuAAAGCUUGGGGUCC	1119	1226
  	AD-26218	GAccccAAGcuuuAGuAAA	461	UUuACuAAAGCUUGGGGUC	1120	1227
  	AD-26651	AccccAAGcuuuAGuAAAu	462	AUUuACuAAAGCUUGGGGU	1121	1228
  	AD-26652	ccccAAGcuuuAGuAAAuA	463	uAUUuACuAAAGCUUGGGG	1122	1229
  	AD-26653	cccAAGcuuuAGuAAAuAu	464	AuAUUuACuAAAGCUUGGG	1123	1230
  	AD-26654	ccAAGcuuuAGuAAAuAuA	465	uAuAUUuACuAAAGCUUGG	1124	1231
  	AD-26655	uAAAuAuAAuGAGGAccuA	466	uAGGUCCUcAUuAuAUUuA	1125	1242
  	AD-26656	AAAuAuAAuGAGGAccuAu	467	AuAGGUCCUcAUuAuAUUU	1126	1243
  	AD-26657	AAuAuAAuGAGGAccuAuA	468	uAuAGGUCCUcAUuAuAUU	1127	1244
  	AD-26658	AuAAuGAGGAccuAuAcuu	469	AAGuAuAGGUCCUcAUuAU	1128	1247
  	AD-26659	AAAcuAcuGuGGAccAcAA	470	UUGUGGUCcAcAGuAGUUU	1129	1271
  	AD-26660	ccAcAAGcAGAGuGcuGAA	471	UUcAGcACUCUGCUUGUGG	1130	1284
  	AD-26661	cAGAGuGcuGAAGGuGcuA	472	uAGcACCUUcAGcACUCUG	1131	1291
  	AD-26662	AGAGuGcuGAAGGuGcuAu	473	AuAGcACCUUcAGcACUCU	1132	1292
  	AD-26663	AuuGuAGAAGcuGGuGGAA	474	UUCcACcAGCUUCuAcAAU	1133	1337
  	AD-26664	uuGuAGAAGcuGGuGGAAu	475	AUUCcACcAGCUUCuAcAA	1134	1338
  	AD-26665	GcuGGuGGAAuGcAAGcuu	476	AAGCUUGcAUUCcACcAGC	1135	1346
  	AD-26666	cuGGuGGAAuGcAAGcuuu	477	AAAGCUUGcAUUCcACcAG	1136	1347
  	AD-26667	AGGAcuucAccuGAcAGAu	478	AUCUGUcAGGUGAAGUCCU	1137	1366
  	AD-26668	cuucAccuGAcAGAuccAA	479	UUGGAUCUGUcAGGUGAAG	1138	1370
  	AD-26669	ccuGAcAGAuccAAGucAA	480	UUGACUUGGAUCUGUcAGG	1139	1375
  	AD-26670	AGAuccAAGucAAcGucuu	481	AAGACGUUGACUUGGAUCU	1140	1381
  	AD-26671	uccAAGucAAcGucuuGuu	482	AAcAAGACGUUGACUUGGA	1141	1384
  	AD-26672	ucuuGuucAGAAcuGucuu	483	AAGAcAGUUCUGAAcAAGA	1142	1396
  	AD-26673	cuuGuucAGAAcuGucuuu	484	AAAGAcAGUUCUGAAcAAG	1143	1397
  	AD-26674	GucuuuGGAcucucAGGAA	485	UUCCUGAGAGUCcAAAGAC	1144	1410
  	AD-26675	ucuuuGGAcucucAGGAAu	486	AUUCCUGAGAGUCcAAAGA	1145	1411
  	AD-26676	uuGGAcucucAGGAAucuu	487	AAGAUUCCUGAGAGUCcAA	1146	1414
  	AD-26677	uGcccAGGGAGAAccccuu	488	AAGGGGUUCUCCCUGGGcA	1147	2371
  	AD-26678	uGGAcucucAGGAAucuuu	489	AAAGAUUCCUGAGAGUCcA	1148	1415
  	AD-26679	ucucAGGAAucuuucAGAu	490	AUCUGAAAGAUUCCUGAGA	1149	1420
  	AD-26680	AAucuuucAGAuGcuGcAA	491	UUGcAGcAUCUGAAAGAUU	1150	1427
  	AD-26681	cuuucAGAuGcuGcAAcuA	492	uAGUUGcAGcAUCUGAAAG	1151	1430
  	AD-26682	uucAGAuGcuGcAAcuAAA	493	UUuAGUUGcAGcAUCUGAA	1152	1432
  	AD-26683	uGcuGcAAcuAAAcAGGAA	494	UUCCUGUUuAGUUGcAGcA	1153	1438
  	AD-26684	uAAAcAGGAAGGGAuGGAA	495	UUCcAUCCCUUCCUGUUuA	1154	1447
  	AD-26685	AGGGAuGGAAGGucuccuu	496	AAGGAGACCUUCcAUCCCU	1155	1456
  	AD-26686	AGGucuccuuGGGAcucuu	497	AAGAGUCCcAAGGAGACCU	1156	1465
  	AD-26687	ucuccuuGGGAcucuuGuu	498	AAcAAGAGUCCcAAGGAGA	1157	1468
  	AD-26688	uGGGAcucuuGuucAGcuu	499	AAGCUGAAcAAGAGUCCcA	1158	1474
  	AD-26689	cuuGuucAGcuucuGGGuu	500	AACCcAGAAGCUGAAcAAG	1159	1481
  	AD-26690	ucAGcuucuGGGuucAGAu	501	AUCUGAACCcAGAAGCUGA	1160	1486
  	AD-26691	GcuucuGGGuucAGAuGAu	502	AUcAUCUGAACCcAGAAGC	1161	1489
  	AD-26692	cuucuGGGuucAGAuGAuA	503	uAUcAUCUGAACCcAGAAG	1162	1490
  	AD-26693	GGccAGGAuGccuuGGGuA	504	uACCcAAGGcAUCCUGGCC	1163	2441
  	AD-26694	uucuGGGuucAGAuGAuAu	505	AuAUcAUCUGAACCcAGAA	1164	1491
  	AD-26695	cuGGGuucAGAuGAuAuAA	506	UuAuAUcAUCUGAACCcAG	1165	1493
  	AD-26696	uGGGuucAGAuGAuAuAAA	507	UUuAuAUcAUCUGAACCcA	1166	1494
  	AD-26697	GucAccuGuGcAGcuGGAA	508	UUCcAGCUGcAcAGGUGAC	1167	1517
  	AD-26698	ucAccuGuGcAGcuGGAAu	509	AUUCcAGCUGcAcAGGUGA	1168	1518
  	AD-26699	cAccuGuGcAGcuGGAAuu	510	AAUUCcAGCUGcAcAGGUG	1169	1519
  	AD-26700	cuGuGcAGcuGGAAuucuu	511	AAGAAUUCcAGCUGcAcAG	1170	1522
  	AD-26701	uGuGcAGcuGGAAuucuuu	512	AAAGAAUUCcAGCUGcAcA	1171	1523
  	AD-26702	GcAGcuGGAAuucuuucuA	513	uAGAAAGAAUUCcAGCUGC	1172	1526
  	AD-26703	cAGcuGGAAuucuuucuAA	514	UuAGAAAGAAUUCcAGCUG	1173	1527
  	AD-26704	uuucuAAccucAcuuGcAA	515	UUGcAAGUGAGGUuAGAAA	1174	1539
  	AD-26705	uucuAAccucAcuuGcAAu	516	AUUGcAAGUGAGGUuAGAA	1175	1540
  	AD-26706	AccucAcuuGcAAuAAuuA	517	uAAUuAUUGcAAGUGAGGU	1176	1545
  	AD-26707	ccucAcuuGcAAuAAuuAu	518	AuAAUuAUUGcAAGUGAGG	1177	1546
  	AD-26708	cucAcuuGcAAuAAuuAuA	519	uAuAAUuAUUGcAAGUGAG	1178	1547
  	AD-26709	GucuGccAAGuGGGuGGuA	520	uACcACCcACUUGGcAGAC	1179	1580
  	AD-26710	ucuGccAAGuGGGuGGuAu	521	AuACcACCcACUUGGcAGA	1180	1581
  	AD-26711	GGGuGGuAuAGAGGcucuu	522	AAGAGCCUCuAuACcACCC	1181	1591
  	AD-26712	AuAGAGGcucuuGuGcGuA	523	uACGcAcAAGAGCCUCuAU	1182	1598
  	AD-26713	ucuuGuGcGuAcuGuccuu	524	AAGGAcAGuACGcAcAAGA	1183	1606
  	AD-26714	cuGGuGAcAGGGAAGAcAu	525	AUGUCUUCCCUGUcACcAG	1184	1629
  	AD-26715	AcAucAcuGAGccuGccAu	526	AUGGcAGGCUcAGUGAUGU	1185	1644
  	AD-26716	GccuGccAucuGuGcucuu	527	AAGAGcAcAGAUGGcAGGC	1186	1654
  	AD-26717	ucuGAccAGccGAcAccAA	528	UUGGUGUCGGCUGGUcAGA	1187	1678
  	AD-26718	GAccAGccGAcAccAAGAA	529	UUCUUGGUGUCGGCUGGUC	1188	1681
  	AD-26719	GAcAccAAGAAGcAGAGAu	530	AUCUCUGCUUCUUGGUGUC	1189	1689
  	AD-26720	AGcAGAGAuGGcccAGAAu	531	AUUCUGGGCcAUCUCUGCU	1190	1699
  	AD-26721	GAuGGcccAGAAuGcAGuu	532	AACUGcAUUCUGGGCcAUC	1191	1705
  	AD-26722	ccAGAAuGcAGuucGccuu	533	AAGGCGAACUGcAUUCUGG	1192	1711
  	AD-26723	AuGcAGuucGccuucAcuA	534	uAGUGAAGGCGAACUGcAU	1193	1716
  	AD-26724	uGcAGuucGccuucAcuAu	535	AuAGUGAAGGCGAACUGcA	1194	1717
  	AD-26725	ucGccuucAcuAuGGAcuA	536	uAGUCcAuAGUGAAGGCGA	1195	1723
  	AD-26726	ucAcuAuGGAcuAccAGuu	537	AACUGGuAGUCcAuAGUGA	1196	1729
  	AD-26727	uGGAcuAccAGuuGuGGuu	538	AACcAcAACUGGuAGUCcA	1197	1735
  	AD-26728	GGAcuAccAGuuGuGGuuA	539	uAACcAcAACUGGuAGUCC	1198	1736
  	AD-26729	GAcuAccAGuuGuGGuuAA	540	UuAACcAcAACUGGuAGUC	1199	1737
  	AD-26730	cAGuuGuGGuuAAGcucuu	541	AAGAGCUuAACcAcAACUG	1200	1743
  	AD-26731	AGuuGuGGuuAAGcucuuA	542	uAAGAGCUuAACcAcAACU	1201	1744
  	AD-26732	AAGcucuuAcAcccAccAu	543	AUGGUGGGUGuAAGAGCUU	1202	1754
  	AD-26733	cAucccAcuGGccucuGAu	544	AUcAGAGGCcAGUGGGAUG	1203	1770
  	AD-26734	AucccAcuGGccucuGAuA	545	uAUcAGAGGCcAGUGGGAU	1204	1771
  	AD-26735	ucccAcuGGccucuGAuAA	546	UuAUcAGAGGCcAGUGGGA	1205	1772
  	AD-26736	uGGccucuGAuAAAGGcuA	547	uAGCCUUuAUcAGAGGCcA	1206	1778
  	AD-26737	ucuGAuAAAGGcuAcuGuu	548	AAcAGuAGCCUUuAUcAGA	1207	1783
  	AD-26738	AuAAAGGcuAcuGuuGGAu	549	AUCcAAcAGuAGCCUUuAU	1208	1787
  	AD-26739	GGcuAcuGuuGGAuuGAuu	550	AAUcAAUCcAAcAGuAGCC	1209	1792
  	AD-26740	uGuuGGAuuGAuucGAAAu	551	AUUUCGAAUcAAUCcAAcA	1210	1798
  	AD-26741	uGccAuuccAcGAcuAGuu	552	AACuAGUCGUGGAAUGGcA	1211	1861
  	AD-26742	uuccAcGAcuAGuucAGuu	553	AACUGAACuAGUCGUGGAA	1212	1866
  	AD-26743	AcGAcuAGuucAGuuGcuu	554	AAGcAACUGAACuAGUCGU	1213	1870
  	AD-26744	AcuAGuucAGuuGcuuGuu	555	AAcAAGcAACUGAACuAGU	1214	1873
  	AD-26745	GuuGcuuGuucGuGcAcAu	556	AUGUGcACGAAcAAGcAAC	1215	1882
  	AD-26746	uGuucGuGcAcAucAGGAu	557	AUCCUGAUGUGcACGAAcA	1216	1888
  	AD-26747	GuucGuGcAcAucAGGAuA	558	uAUCCUGAUGUGcACGAAC	1217	1889
  	AD-26748	GGuGGGAcAcAGcAGcAAu	559	AUUGCUGCUGUGUCCcACC	1218	1928
  	AD-26749	GuGGGAcAcAGcAGcAAuu	560	AAUUGCUGCUGUGUCCcAC	1219	1929
  	AD-26750	uGGGAcAcAGcAGcAAuuu	561	AAAUUGCUGCUGUGUCCcA	1220	1930
  	AD-26751	GGGGuccGcAuGGAAGAAA	562	UUUCUUCcAUGCGGACCCC	1221	1955
  	AD-26752	GGGuccGcAuGGAAGAAAu	563	AUUUCUUCcAUGCGGACCC	1222	1956
  	AD-26753	ucAcAuccuAGcucGGGAu	564	AUCCCGAGCuAGGAUGUGA	1223	1999
  	AD-26754	cAuccuAGcucGGGAuGuu	565	AAcAUCCCGAGCuAGGAUG	1224	2002
  	AD-26755	uAGcucGGGAuGuucAcAA	566	UUGUGAAcAUCCCGAGCuA	1225	2007
  	AD-26756	GGGAuGuucAcAAccGAAu	567	AUUCGGUUGUGAAcAUCCC	1226	2013
  	AD-26757	GGAuGuucAcAAccGAAuu	568	AAUUCGGUUGUGAAcAUCC	1227	2014
  	AD-26758	cAGAGGAcuAAAuAccAuu	569	AAUGGuAUUuAGUCCUCUG	1228	2038
  	AD-26759	GGAcuAAAuAccAuuccAu	570	AUGGAAUGGuAUUuAGUCC	1229	2042
  	AD-26760	uAAAuAccAuuccAuuGuu	571	AAcAAUGGAAUGGuAUUuA	1230	2046
  	AD-26761	AAAuAccAuuccAuuGuuu	572	AAAcAAUGGAAUGGuAUUU	1231	2047
  	AD-26762	AuuGuuuGuGcAGcuGcuu	573	AAGcAGCUGcAcAAAcAAU	1232	2059
  	AD-26763	uuGuuuGuGcAGcuGcuuu	574	AAAGcAGCUGcAcAAAcAA	1233	2060
  	AD-26764	uGuuuGuGcAGcuGcuuuA	575	uAAAGcAGCUGcAcAAAcA	1234	2061
  	AD-26765	GuuuGuGcAGcuGcuuuAu	576	AuAAAGcAGCUGcAcAAAC	1235	2062
  	AD-26766	uuuGuGcAGcuGcuuuAuu	577	AAuAAAGcAGCUGcAcAAA	1236	2063
  	AD-26767	AGcuGcuuuAuucucccAu	578	AUGGGAGAAuAAAGcAGCU	1237	2070
  	AD-26768	GcuGcuuuAuucucccAuu	579	AAUGGGAGAAuAAAGcAGC	1238	2071
  	AD-26769	uuuAuucucccAuuGAAAA	580	UUUUcAAUGGGAGAAuAAA	1239	2076
  	AD-26770	AuucucccAuuGAAAAcAu	581	AUGUUUUcAAUGGGAGAAU	1240	2079
  	AD-26771	ucccAuuGAAAAcAuccAA	582	UUGGAUGUUUUcAAUGGGA	1241	2083
  	AD-26772	uGcAGGGGuccucuGuGAA	583	UUcAcAGAGGACCCCUGcA	1242	2110
  	AD-26773	AcuuGcucAGGAcAAGGAA	584	UUCCUUGUCCUGAGcAAGU	1243	2128
  	AD-26774	cAGcuccucuGAcAGAGuu	585	AACUCUGUcAGAGGAGCUG	1244	2178
  	AD-26775	AGcuccucuGAcAGAGuuA	586	uAACUCUGUcAGAGGAGCU	1245	2179
  	AD-26776	uccucuGAcAGAGuuAcuu	587	AAGuAACUCUGUcAGAGGA	1246	2182
  	AD-26777	AcAGAGuuAcuucAcucuA	588	uAGAGUGAAGuAACUCUGU	1247	2189
  	AD-26778	AGuuAcuucAcucuAGGAA	589	UUCCuAGAGUGAAGuAACU	1248	2193
  	AD-26779	GuuAcuucAcucuAGGAAu	590	AUUCCuAGAGUGAAGuAAC	1249	2194
  	AD-26780	AcuucAcucuAGGAAuGAA	591	UUcAUUCCuAGAGUGAAGU	1250	2197
  	AD-26781	GcuGcuGuuuuGuuccGAA	592	UUCGGAAcAAAAcAGcAGC	1251	2234
  	AD-26782	cuGcuGuuuuGuuccGAAu	593	AUUCGGAAcAAAAcAGcAG	1252	2235
  	AD-26783	GucuGAGGAcAAGccAcAA	594	UUGUGGCUUGUCCUcAGAC	1253	2254
  	AD-26784	uGAGGAcAAGccAcAAGAu	595	AUCUUGUGGCUUGUCCUcA	1254	2257
  	AD-26785	AcAAGccAcAAGAuuAcAA	596	UUGuAAUCUUGUGGCUUGU	1255	2262
  	AD-26786	AGccAcAAGAuuAcAAGAA	597	UUCUUGuAAUCUUGUGGCU	1256	2265
  	AD-26787	AGAuuAcAAGAAAcGGcuu	598	AAGCCGUUUCUUGuAAUCU	1257	2272
  	AD-26788	cAAGAAAcGGcuuucAGuu	599	AACUGAAAGCCGUUUCUUG	1258	2278
  	AD-26789	AGcuGAccAGcucucucuu	600	AAGAGAGAGCUGGUcAGCU	1259	2298
  	AD-26790	AccAGcucucucuucAGAA	601	UUCUGAAGAGAGAGCUGGU	1260	2303
  	AD-26791	uAuuGGuGcccAGGGAGAA	602	UUCUCCCUGGGcACcAAuA	1261	2365
  	AD-26792	cAGGGAGAAccccuuGGAu	603	AUCcAAGGGGUUCUCCCUG	1262	2375
  	AD-26793	AGGGAGAAccccuuGGAuA	604	uAUCcAAGGGGUUCUCCCU	1263	2376
  	AD-26794	ccuuGGAuAucGccAGGAu	605	AUCCUGGCGAuAUCcAAGG	1264	2386
  	AD-26795	uAucGccAGGAuGAuccuA	606	uAGGAUcAUCCUGGCGAuA	1265	2393
  	AD-26796	GccAGGAuGAuccuAGcuA	607	uAGCuAGGAUcAUCCUGGC	1266	2397
  	AD-26797	ccAGGAuGAuccuAGcuAu	608	AuAGCuAGGAUcAUCCUGG	1267	2398
  	AD-26798	GAuGAuccuAGcuAucGuu	609	AACGAuAGCuAGGAUcAUC	1268	2402
  	AD-26799	AuccuAGcuAucGuucuuu	610	AAAGAACGAuAGCuAGGAU	1269	2406
  	AD-26800	uccuAGcuAucGuucuuuu	611	AAAAGAACGAuAGCuAGGA	1270	2407
  	AD-26801	ucuuuucAcucuGGuGGAu	612	AUCcACcAGAGUGAAAAGA	1271	2420
  	AD-26802	cuuuucAcucuGGuGGAuA	613	uAUCcACcAGAGUGAAAAG	1272	2421
  	AD-26803	uuuucAcucuGGuGGAuAu	614	AuAUCcACcAGAGUGAAAA	1273	2422
  	AD-26804	uGGuGGAuAuGGccAGGAu	615	AUCCUGGCcAuAUCcACcA	1274	2431
  	AD-26805	GAuAuGGccAGGAuGccuu	616	AAGGcAUCCUGGCcAuAUC	1275	2436
  	AD-26806	ccuuGGGuAuGGAccccAu	617	AUGGGGUCcAuACCcAAGG	1276	2451
  	AD-26807	uGGGuAuGGAccccAuGAu	618	AUcAUGGGGUCcAuACCcA	1277	2454
  	AD-26808	uuGuAAAcuuGAuuAAcuA	619	uAGUuAAUcAAGUUuAcAA	1278	675
  	AD-26809	uGuAAAcuuGAuuAAcuAu	620	AuAGUuAAUcAAGUUuAcA	1279	676
  	AD-26810	AAAcuuGAuuAAcuAucAA	621	UUGAuAGUuAAUcAAGUUU	1280	679
  	AD-26811	uAuGGAccccAuGAuGGAA	622	UUCcAUcAUGGGGUCcAuA	1281	2458
  	AD-26812	GGAccccAuGAuGGAAcAu	623	AUGUUCcAUcAUGGGGUCC	1282	2461
  	AD-26813	ccAuGAuGGAAcAuGAGAu	624	AUCUcAUGUUCcAUcAUGG	1283	2466
  	AD-26814	AccAcccuGGuGcuGAcuA	625	uAGUcAGcACcAGGGUGGU	1284	2493
  	AD-26815	ccAcccuGGuGcuGAcuAu	626	AuAGUcAGcACcAGGGUGG	1285	2494
  	AD-26816	uGcuGAcuAuccAGuuGAu	627	AUcAACUGGAuAGUcAGcA	1286	2503
  	AD-26817	AGuuGAuGGGcuGccAGAu	628	AUCUGGcAGCCcAUcAACU	1287	2515
  	AD-26818	uGcccAGGAccucAuGGAu	629	AUCcAUGAGGUCCUGGGcA	1288	2542
  	AD-26819	GcAAucAGcuGGccuGGuu	630	AACcAGGCcAGCUGAUUGC	1289	2580
  	AD-26820	cAAucAGcuGGccuGGuuu	631	AAACcAGGCcAGCUGAUUG	1290	2581
  	AD-26821	GGuuuGAuAcuGAccuGuA	632	uAcAGGUcAGuAUcAAACC	1291	2595
  	AD-26822	AuAcuGAccuGuAAAucAu	633	AUGAUUuAcAGGUcAGuAU	1292	2601
  	AD-26823	uGAccuGuAAAucAuccuu	634	AAGGAUGAUUuAcAGGUcA	1293	2605
  	AD-26824	GAccuGuAAAucAuccuuu	635	AAAGGAUGAUUuAcAGGUC	1294	2606
  	AD-26825	AccuGuAAAucAuccuuuA	636	uAAAGGAUGAUUuAcAGGU	1295	2607
  	AD-26826	AAuAcAAAuGAuGuAGAAA	637	UUUCuAcAUcAUUUGuAUU	1296	878
  	AD-26900	uuuuAAGAAuAucuGuAAu	638	AUuAcAGAuAUUCUuAAAA	1297	2745
  	AD-26901	uAcAGcAAuuucuAAuuuu	639	AAAAUuAGAAAUUGCUGuA	1298	2872
  	AD-26902	cAcuAAuucAuAAucAcuc	640	GAGUGAUuAUGAAUuAGUG	1299	2915
  	AD-26903	AcuAAuucAuAAucAcucu	641	AGAGUGAUuAUGAAUuAGU	1300	2916
  	AD-26904	uAAuucAuAAucAcucuAA	642	UuAGAGUGAUuAUGAAUuA	1301	2918
  	AD-26905	AAuucAuAAucAcucuAAu	643	AUuAGAGUGAUuAUGAAUU	1302	2919
  	AD-26906	AAuuGuAAucuGAAuAAAG	644	CUUuAUUcAGAUuAcAAUU	1303	2939
  	AD-26907	uuuGuAuAAAAuAGAcAAA	645	UUUGUCuAUUUuAuAcAAA	1304	2978
  	AD-26908	uuGuAuAAAAuAGAcAAAu	646	AUUUGUCuAUUUuAuAcAA	1305	2979
  	AD-26909	uGuAuAAAAuAGAcAAAuA	647	uAUUUGUCuAUUUuAuAcA	1306	2980
  	AD-26910	GuAuAAAAuAGAcAAAuAG	648	CuAUUUGUCuAUUUuAuAC	1307	2981
  	AD-26911	AuAAAAuAGAcAAAuAGAA	649	UUCuAUUUGUCuAUUUuAU	1308	2983
  	AD-26912	uAAAAuAGAcAAAuAGAAA	650	UUUCuAUUUGUCuAUUUuA	1309	2984
  	AD-26913	AAAuAGAcAAAuAGAAAAu	651	AUUUUCuAUUUGUCuAUUU	1310	2986
  	AD-26914	uGGGAuAuGuAuGGGuAGG	652	CCuACCcAuAcAuAUCCcA	1311	3081
  	AD-26915	GGGAuAuGuAuGGGuAGGG	653	CCCuACCcAuAcAuAUCCC	1312	3082
  	AD-26916	cuAAuucAuAAucAcucuA	654	uAGAGUGAUuAUGAAUuAG	1313	2917
  	AD-26917	AAAuAGAAAAuGGuccAAu	655	AUUGGACcAUUUUCuAUUU	1314	2994
  	AD-26918	AAuAGAAAAuGGuccAAuu	656	AAUUGGACcAUUUUCuAUU	1315	2995
  	AD-26919	uuuGGAcAGuuuAccAGuu	657	AACUGGuAAACUGUCcAAA	1316	3134
  	AD-26920	AuucuuucuAAccucAcuu	658	AAGUGAGGUuAGAAAGAAU	1317	1535
  	AD-26921	uGGAuuGAuucGAAAucuu	659	AAGAUUUCGAAUcAAUCcA	1318	1801
  	Set1 254	ccAtAcAActGttttGAAA	6141	TTTcAAAAcAGTTGtATGG	6309	236
  	A22 S26
  	Set1 703	GAttAActAtcAAGAtGAt	6142	ATcATCTTGAtAGTtAATC	6310	685
  	A22 S26
  	Set1 709	ctAtcAAGAtGAtGcAGAA	6143	TTCTGcATcATCTTGAtAG	6311	691
  	A22 S26
  	Set1 895	GAAtAcAAAtGAtGtAGAA	6144	TTCtAcATcATTTGtATTC	6312	877
  	A22 S26
  	Set1	tGttGGAttGAttcGAAAt	6145	ATTTCGAATcAATCcAAcA	6313	1798
  	1816 A22
  	S26
  	Set1	GGGtccGcAtGGAAGAAAt	6146	ATTTCTTCcATGCGGACCC	6314	1956
  	1974 A22
  	S26
  	Set1	tcctAGctAtcGttctttt	6147	AAAAGAACGAtAGCtAGGA	6315	2407
  	2425 A22
  	S26
  	Set1	AAGtGAAGAAtGcAcAAGA	6148	TCTTGTGcATTCTTcACTT	6316	3128
  	3146 A22
  	S26
  	Set1 889	cAtGcAGAAtAcAAAtGAt	6149	ATcATTTGtATTCTGcATG	6317	871
  	A22 S26
  	Set1	ActGttGGAttGAttcGAA	6150	TTCGAATcAATCcAAcAGT	6318	1796
  	1814 A22
  	S26
  	Set1	GAccccAAGctttAGtAAA	6151	TTtACtAAAGCTTGGGGTC	6319	1227
  	1245 A22
  	S26
  	Set1	AGccttGcttGttAAAttt	6152	AAATTtAAcAAGcAAGGCT	6320	3178
  	3196 A22
  	S26
  	Set1	ttcAGAtGctGcAActAAA	6153	TTtAGTTGcAGcATCTGAA	6321	1432
  	1450 A22
  	S26
  	Set1	AtcAcAAGAtGGAAtttAt	6154	AtAAATTCcATCTTGTGAT	6322	3151
  	3169 A22
  	S26
  	Set1	AAtAGAAAAtGGtccAAtt	6155	AATTGGACcATTTTCtATT	6323	3459
  	3477 A22
  	S26
  	Set1 865	GAtGGtGtctGctAttGtA	6156	tAcAAtAGcAGAcACcATC	6324	847
  	A22 S26
  	Set1	ccAAGctttAGtAAAtAtA	6157	tAtATTtACtAAAGCTTGG	6325	1231
  	1249 A22
  	S26
  	Set1	cAAGctttAGtAAAtAtAA	6158	TtAtATTtACtAAAGCTTG	6326	1232
  	1250 A22
  	S26
  	Set1	ctctGAcAGAGttActtcA	6159	TGAAGtAAcTcTGTcAGAG	6327	2184
  	2202 A22
  	S26
  	Set1	cAGctGGAAttctttctAA	6160	TtAGAAAGAATTCcAGCTG	6328	1527
  	1545 A22
  	S26
  	Set1	GActAccAGttGtGGttAA	6161	TtAACcAcAACTGGtAGTC	6329	1737
  	1755 A22
  	S26
  	Set1 254	CCATACAACTGTTTTGAAA	6162	TTTCAAAACAGTTGTATGG	6330	236
  	A25 S27
  	Set1 703	GATTAACTATCAAGATGAT	6163	ATCATCTTGATAGTTAATC	6331	685
  	A25 S27
  	Set1 709	CTATCAAGATGATGCAGAA	6164	TTCTGCATCATCTTGATAG	6332	691
  	A25 S27
  	Set1 895	GAATACAAATGATGTAGAA	6165	TTCTACATCATTTGTATTC	6333	877
  	A25 S27
  	Set1	TGTTGGATTGATTCGAAAT	6166	ATTTCGAATCAATCCAACA	6334	1798
  	1816 A25
  	S27
  	Set1	GGGTCCGCATGGAAGAAAT	6167	ATTTCTTCCATGCGGACCC	6335	1956
  	1974 A25
  	S27
  	Set1	TCCTAGCTATCGTTCTTTT	6168	AAAAGAACGATAGCTAGGA	6336	2407
  	2425 A25
  	S27
  	Set1	AAGTGAAGAATGCACAAGA	6169	TCTTGTGCATTCTTCACTT	6337	3128
  	3146 A25
  	S27
  	Set1 889	CATGCAGAATACAAATGAT	6170	ATCATTTGTATTCTGCATG	6338	871
  	A25 S27
  	Set1	ACTGTTGGATTGATTCGAA	6171	TTCGAATCAATCCAACAGT	6339	1796
  	1814 A25
  	S27
  	Set1	GACCCCAAGCTTTAGTAAA	6172	TTTACTAAAGCTTGGGGTC	6340	1227
  	1245 A25
  	S27
  	Set1	AGCCTTGCTTGTTAAATTT	6173	AAATTTAACAAGCAAGGCT	6341	3178
  	3196 A25
  	S27
  	Set1	TTCAGATGCTGCAACTAAA	6174	TTTAGTTGCAGCATCTGAA	6342	1432
  	1450 A25
  	S27
  	Set1	ATCACAAGATGGAATTTAT	6175	ATAAATTCCATCTTGTGAT	6343	3151
  	3169 A25
  	S27
  	Set1	AATAGAAAATGGTCCAATT	6176	AATTGGACCATTTTCTATT	6344	3459
  	3477 A25
  	S27
  	Set1 865	GATGGTGTCTGCTATTGTA	6177	TACAATAGCAGACACCATC	6345	847
  	A25 S27
  	Set1	CCAAGCTTTAGTAAATATA	6178	TATATTTACTAAAGCTTGG	6346	1231
  	1249 A25
  	S27
  	Set1	CAAGCTTTAGTAAATATAA	6179	TTATATTTACTAAAGCTTG	6347	1232
  	1250 A25
  	S27
  	Set1	CTCTGACAGAGTTACTTCA	6180	TGAAGTAACTCTGTCAGAG	6348	2184
  	2202 A25
  	S27
  	Set1	CAGCTGGAATTCTTTCTAA	6181	TTAGAAAGAATTCCAGCTG	6349	1527
  	1545 A25
  	S27
  	Set1	GACTACCAGTTGTGGTTAA	6182	TTAACCACAACTGGTAGTC	6350	1737
  	1755 A25
  	S27
  	Set1 254	ccAtAcAActGttttGAAA	6183	TTtcAAAAcAGttGtAtGG	6351	236
  	A LO V1
  	S26
  	Set1 703	GAttAActAtcAAGAtGAt	6184	ATcAtcttGAtAGTtAAtc	6352	685
  	A LO V1
  	S26
  	Set1 709	ctAtcAAGAtGAtGcAGAA	6185	TTctGcAtcAtctTGAtAG	6353	691
  	A LO V1
  	S26
  	Set1 895	GAAtAcAAAtGAtGtAGAA	6186	TTctAcAtcAtttGtAttc	6354	877
  	A LO V1
  	S26
  	Set1	tGttGGAttGAttcGAAAt	6187	ATttcGAAtcAAtCcAAcA	6355	1798
  	1816 A
  	LO V1
  	S26
  	Set1	GGGtccGcAtGGAAGAAAt	6188	ATttcttccAtGcGGAccc	6356	1956
  	1974 A
  	LO V1
  	S26
  	Set1	tcctAGctAtcGttctttt	6189	AAAAGAAcGAtAGCtAGGA	6357	2407
  	2425 A
  	LO V1
  	S26
  	Set1	AAGtGAAGAAtGcAcAAGA	6190	TCttGtGcAttctTcActt	6358	3128
  	3146 A
  	LO V1
  	S26
  	Set1 889	cAtGcAGAAtAcAAAtGAt	6191	ATcAtttGtAttcTGcAtG	6359	871
  	A LO V1
  	S26
  	Set1	ActGttGGAttGAttcGAA	6192	TTcGAAtcAAtccAAcAGt	6360	1796
  	1814 A
  	LO V1
  	S26
  	Set1	GAccccAAGctttAGtAAA	6193	TTtActAAAGcttGGGGtc	6361	1227
  	1245 A
  	LO V1
  	S26
  	Set1	AGccttGcttGttAAAttt	6194	AAAtttAAcAAGcAAGGct	6362	3178
  	3196 A
  	LO V1
  	S26
  	Set1	ttcAGAtGctGcAActAAA	6195	TTtAGttGcAGcATctGAA	6363	1432
  	1450 A
  	LO V1
  	S26
  	Set1	AtcAcAAGAtGGAAtttAt	6196	ATAAAttccAtctTGtGAt	6364	3151
  	3169 A
  	LO V1
  	S26
  	Set1	AAtAGAAAAtGGtccAAtt	6197	AAttGGAccAtttTctAtt	6365	3459
  	3477 A
  	LO V1
  	S26
  	Set1 865	GAtGGtGtctGctAttGtA	6198	TAcAAtAGcAGAcAccAtc	6366	847
  	A LO V1
  	S26
  	Set1	ccAAGctttAGtAAAtAtA	6199	TAtAtttActAAAGcttGG	6367	1231
  	1249 A
  	LO V1
  	S26
  	Set1	cAAGctttAGtAAAtAtAA	6200	TTAtAtttActAAAGcttG	6368	1232
  	1250 A
  	LO V1
  	S26
  	Set1	ctctGAcAGAGttActtcA	6201	TGAAGtAActctGTcAGAG	6369	2184
  	2202 A
  	LO V1
  	S26
  	Set1	cAGctGGAAttctttctAA	6202	TTAGAAAGAAttcCAGctG	6370	1527
  	1545 A
  	LO V1
  	S26
  	Set1	GActAccAGttGtGGttAA	6203	TTAAccAcAActGGtAGtc	6371	1737
  	1755 A
  	LO V1
  	S26
  	Set1 254	ccAtACAaCTGtTTtGAaa	6204	TTtCAAaACaGTtGTATgg	6372	236
  	A LO V2
  	S LO V1
  	Set1 703	gaTtAACtATCaAGaTGat	6205	ATcATCtTGaTAgTTAAtc	6373	685
  	A LO V2
  	S LO V1
  	Set1 709	ctAtCAAgATGaTGcAGaa	6206	TTcTGCaTCaTCtTGATag	6374	691
  	A LO V2
  	S LO V1
  	Set1 895	gaAtACAaATGaTGtAGaa	6207	TTcTACaTCaTTtGTATtc	6375	877
  	A LO V2
  	S LO V1
  	Set1	tgTtGGAtTGAtTCgAAat	6208	ATtTCGaATcAAtCCAAca	6376	1798
  	1816 A
  	LO V2 S
  	LO V1
  	Set1	ggGtCCGcATGgAAgAAat	6209	ATtTCTtCCaTGcGGACcc	6377	1956
  	1974 A
  	LO V2 S
  	LO V1
  	Set1	tcCtAGCtATCgTTcTTtt	6210	AAaAGAaCGaTAgCTAGga	6378	2407
  	2425 A
  	LO V2 S
  	LO V1
  	Set1	aaGtGAAgAATgCAcAAga	6211	TCtTGTgCAtTCtTCACtt	6379	3128
  	3146 A
  	LO V2 S
  	LO V1
  	Set1 889	caTgCAGaATAcAAaTGat	6212	ATcATTtGTaTTcTGCAtg	6380	871
  	A LO V2
  	S LO V1
  	Set1	acTgTTGgATTgATtCGaa	6213	TTcGAAtCAaTCcAACAgt	6381	1796
  	1814 A
  	LO V2 S
  	LO V1
  	Set1	gaCcCCAaGCTtTAgTAaa	6214	TTtACTaAAgCTtGGGGtc	6382	1227
  	1245 A
  	LO V2 S
  	LO V1
  	Set1	agCcTTGcTTGtTAaATtt	6215	AAaTTTaACaAGcAAGGct	6383	3178
  	3196 A
  	LO V2 S
  	LO V1
  	Set1	ttCaGATgCTGcAAcTAaa	6216	TTtAGTtGCaGCaTCTGaa	6384	1432
  	1450 A
  	LO V2 S
  	LO V1
  	Set1	atCaCAAgATGgAAtTTat	6217	ATaAATtCCaTCtTGTGat	6385	3151
  	3169 A
  	LO V2 S
  	LO V1
  	Set1	aaTaGAAaATGgTCcAAtt	6218	AAtTGGaCCaTTtTCTAtt	6386	3459
  	3477 A
  	LO V2 S
  	LO V1
  	Set1 865	gaTgGTGtCTGcTAtTGta	6219	TAcAATaGCaGAcACCAtc	6387	847
  	A LO V2
  	S LO V1
  	Set1	ccAaGCTtTAGtAAaTAta	6220	TAtATTtACtAAaGCTTgg	6388	1231
  	1249 A
  	LO V2 S
  	LO V1
  	Set1	caAgCTTtAGTaAAtATaa	6221	TTaTATtTAcTAaAGCTtg	6389	1232
  	1250 A
  	LO V2 S
  	LO V1
  	Set1	ctCtGACaGAGtTAcTTca	6222	TGaAGTaACtCTgTCAGag	6390	2184
  	2202 A
  	LO V2 S
  	LO V1
  	Set1	caGcTGGaATTcTTtCTaa	6223	TTaGAAaGAaTTcCAGCtg	6391	1527
  	1545 A
  	LO V2 S
  	LO V1
  	Set1	gaCtACCaGTTgTGgTTaa	6224	TTaACCaCAaCTgGTAGtc	6392	1737
  	1755 A
  	LO V2 S
  	LO V1
  	Set2 254	ccAtACAaCTGtTTtGAaa	6225	TTtCAAaACaGTtGTATgg	6393	236
  	A LO V3
  	S LO V2
  	Set2 703	gaTtAACtATCaAGaTGat	6226	ATcATCtTGaTAgTTAAtc	6394	685
  	A LO V3
  	S LO V2
  	Set2 709	ctAtCAAgATGaTGcAGaa	6227	TTcTGCaTCaTCtTGATag	6395	691
  	A LO V3
  	S LO V2
  	Set2 895	gaAtACAaATGaTGtAGaa	6228	TTcTACaTCaTTtGTATtc	6396	877
  	A LO V3
  	S LO V2
  	Set2	tgTtGGAtTGAtTCgAAat	6229	ATtTCGaATcAAtCCAAca	6397	1798
  	1816 A
  	LO V3 S
  	LO V2
  	Set2	ggGtCCGcATGgAAgAAat	6230	ATtTCTtCCaTGcGGACcc	6398	1956
  	1974 A
  	LO V3 S
  	LO V2
  	Set2	tcCtAGCtATCgTTcTTtt	6231	AAaAGAaCGaTAgCTAGga	6399	2407
  	2425 A
  	LO V3 S
  	LO V2
  	Set2	aaGtGAAgAATgCAcAAga	6232	TCtTGTgCAtTCtTCACtt	6400	3128
  	3146 A
  	LO V3 S
  	LO V2
  	Set2 889	caTgCAGaATAcAAaTGat	6233	ATcATTtGTaTTcTGCAtg	6401	871
  	A LO V3
  	S LO V2
  	Set2	acTgTTGgATTgATtCGaa	6234	TTcGAAtCAaTCcAACAgt	6402	1796
  	1814 A
  	LO V3 S
  	LO V2
  	Set2	gaCcCCAaGCTtTAgTAaa	6235	TTtACTaAAgCTtGGGGtc	6403	1227
  	1245 A
  	LO V3 S
  	LO V2
  	Set2	agCcTTGcTTGtTAaATtt	6236	AAaTTTaACaAGcAAGGct	6404	3178
  	3196 A
  	LO V3 S
  	LO V2
  	Set2	ttCaGATgCTGcAAcTAaa	6237	TTtAGTtGCaGCaTCTGaa	6405	1432
  	1450 A
  	LO V3 S
  	LO V2
  	Set2	atCaCAAgATGgAAtTTat	6238	ATaAATtCCaTCtTGTGat	6406	3151
  	3169 A
  	LO V3 S
  	LO V2
  	Set2	aaTaGAAaATGgTCcAAtt	6239	AAtTGGaCCaTTtTCTAtt	6407	3459
  	3477 A
  	LO V3 S
  	LO V2
  	Set2 865	gaTgGTGtCTGcTAtTGta	6240	TAcAATaGCaGAcACCAtc	6408	847
  	A LO V3
  	S LO V2
  	Set2	ccAaGCTtTAGtAAaTAta	6241	TAtATTtACtAAaGCTTgg	6409	1231
  	1249 A
  	LO V3 S
  	LO V2
  	Set2	caAgCTTtAGTaAAtATaa	6242	TTaTATtTAcTAaAGCTtg	6410	1232
  	1250 A
  	LO V3 S
  	LO V2
  	Set2	ctCtGACAGAGTTAcTTca	6243	TGaAGTaACtCTgTCAGag	6411	2184
  	2202 A
  	LO V3 S
  	LO V2
  	Set2	caGcTGGaATTcTTtCTaa	6244	TTaGAAaGAaTTcCAGCtg	6412	1527
  	1545 A
  	LO V3 S
  	LO V2
  	Set2	gaCtACCaGTTgTGgTTaa	6245	TTaACCaCAaCTgGTAGtc	6413	1737
  	1755 A
  	LO V3 S
  	LO V2
  	Set2 254	ccAtACAaCTGtTTtGAaa	6246	tTtCAAaACaGTtGTATgg	6414	236
  	A LO V4
  	S LO V1
  	Set2 703	gaTtAACtATCaAGaTGat	6247	aTcATCtTGaTAgTTAAtc	6415	685
  	A LO V4
  	S LO V1
  	Set2 709	ctAtCAAgATGaTGcAGaa	6248	tTcTGCaTCaTCtTGATag	6416	691
  	A LO V4
  	S LO V1
  	Set2 895	gaAtACAaATGaTGtAGaa	6249	tTcTACaTCaTTtGTATtc	6417	877
  	A LO V4
  	S LO V1
  	Set2	tgTtGGAtTGAtTCgAAat	6250	aTtTCGaATcAAtCCAAca	6418	1798
  	1816 A
  	LO V4 S
  	LO V1
  	Set2	ggGtCCGcATGgAAgAAat	6251	aTtTCTtCCaTGcGGACcc	6419	1956
  	1974 A
  	LO V4 S
  	LO V1
  	Set2	tcCtAGCtATCgTTcTTtt	6252	aAaAGAaCGaTAgCTAGga	6420	2407
  	2425 A
  	LO V4 S
  	LO V1
  	Set2	aaGtGAAgAATgCAcAAga	6253	tCtTGTgCAtTCtTCACtt	6421	3128
  	3146 A
  	LO V4 S
  	LO V1
  	Set2 889	caTgCAGaATAcAAaTGat	6254	aTcATTtGTaTTcTGCAtg	6422	871
  	A LO V4
  	S LO V1
  	Set2	acTgTTGgATTgATtCGaa	6255	tTcGAAtCAaTCcAACAgt	6423	1796
  	1814 A
  	LO V4 S
  	LO V1
  	Set2	gaCcCCAaGCTtTAgTAaa	6256	tTtACTaAAgCTtGGGGtc	6424	1227
  	1245 A
  	LO V4 S
  	LO V1
  	Set2	agCcTTGcTTGtTAaATtt	6257	aAaTTTaACaAGcAAGGct	6425	3178
  	3196 A
  	LO V4 S
  	LO V1
  	Set2	ttCaGATgCTGcAAcTAaa	6258	tTtAGTtGCaGCaTCTGaa	6426	1432
  	1450 A
  	LO V4 S
  	LO V1
  	Set2	atCaCAAgATGgAAtTTat	6259	aTaAATtCCaTCtTGTGat	6427	3151
  	3169 A
  	LO V4 S
  	LO V1
  	Set2	aaTaGAAaATGgTCcAAtt	6260	aAtTGGaCCaTTtTCTAtt	6428	3459
  	3477 A
  	LO V4 S
  	LO V1
  	Set2 865	gaTgGTGtCTGcTAtTGta	6261	tAcAATaGCaGAcACCAtc	6429	847
  	A LO V4
  	S LO V1
  	Set2	ccAaGCTtTAGtAAaTAta	6262	tAtATTtACtAAaGCTTgg	6430	1231
  	1249 A
  	LO V4 S
  	LO V1
  	Set2	caAgCTTtAGTaAAtATaa	6263	tTaTATtTAcTAaAGCTtg	6431	1232
  	1250 A
  	LO V4 S
  	LO V1
  	Set2	ctCtGACaGAGtTAcTTca	6264	tGaAGTaACtCTgTCAGag	6432	2184
  	2202 A
  	LO V4 S
  	LO V1
  	Set2	caGcTGGaATTcTTtCTaa	6265	tTaGAAaGAaTTcCAGCtg	6433	1527
  	1545 A
  	LO V4 S
  	LO V1
  	Set2	gaCtACCaGTTgTGgTTaa	6266	tTaACCaCAaCTgGTAGtc	6434	1737
  	1755 A
  	LO V4 S
  	LO V1
  	Set2 254	ccAtACAaCTGtTTtGAaa	6267	tTtCAAaACaGTtGTATgg	6435	236
  	A LO V5
  	S LO V1
  	Set2 703	gaTtAACtATCaAGaTGat	6268	aTcATCtTGaTAgTTAAtc	6436	685
  	A LO V5
  	S LO V1
  	Set2 709	ctAtCAAgATGaTGcAGaa	6269	tTcTGCaTCaTCtTGATag	6437	691
  	A LO V5
  	S LO V1
  	Set2 895	gaAtACAaATGaTGtAGaa	6270	tTcTACaTCaTTtGTATtc	6438	877
  	A LO V5
  	S LO V1
  	Set2	tgTtGGAtTGAtTCgAAat	6271	aTtTCGaATcAAtCCAAca	6439	1798
  	1816 A
  	LO V5 S
  	LO V1
  	Set2	ggGtCCGcATGgAAgAAat	6272	aTtTCTtCCaTGcGGACcc	6440	1956
  	1974 A
  	LO V5 S
  	LO V1
  	Set2	tcCtAGCtATCgTTcTTtt	6273	aAaAGAaCGaTAgCTAGga	6441	2407
  	2425 A
  	LO V5 S
  	LO V1
  	Set2	aaGtGAAgAATgCAcAAga	6274	tCtTGTgCAtTCtTCACtt	6442	3128
  	3146 A
  	LO V5 S
  	LO V1
  	Set2 889	caTgCAGaATAcAAaTGat	6275	aTcATTtGTaTTcTGCAtg	6443	871
  	A LO V5
  	S LO V1
  	Set2	acTgTTGgATTgATtCGaa	6276	tTcGAAtCAaTCcAACAgt	6444	1796
  	1814 A
  	LO V5 S
  	LO V1
  	Set2	gaCcCCAaGCTtTAgTAaa	6277	tTtACTaAAgCTtGGGGtc	6445	1227
  	1245 A
  	LO V5 S
  	LO V1
  	Set2	agCcTTGcTTGtTAaATtt	6278	aAaTTTaACaAGcAAGGct	6446	3178
  	3196 A
  	LO V5 S
  	LO V1
  	Set2	ttCaGATgCTGcAAcTAaa	6279	tTtAGTtGCaGCaTCTGaa	6447	1432
  	1450 A
  	LO V5 S
  	LO V1
  	Set2	atCaCAAgATGgAAtTTat	6280	aTaAATtCCaTCtTGTGat	6448	3151
  	3169 A
  	LO V5 S
  	LO V1
  	Set2	aaTaGAAaATGgTCcAAtt	6281	aAtTGGaCCaTTtTCTAtt	6449	3459
  	3477 A
  	LO V5 S
  	LO V1
  	Set2 865	gaTgGTGtCTGcTAtTGta	6282	tAcAATaGCaGAcACCAtc	6450	847
  	A LO V5
  	S LO V1
  	Set2	ccAaGCTtTAGtAAaTAta	6283	tAtATTtACtAAaGCTTgg	6451	1231
  	1249 A
  	LO V5 S
  	LO V1
  	Set2	caAgCTTtAGTaAAtATaa	6284	tTaTATtTAcTAaAGCTtg	6452	1232
  	1250 A
  	LO V5 S
  	LO V1
  	Set2	ctCtGACaGAGtTAcTTca	6285	tGaAGTaACtCTgTCAGag	6453	2184
  	2202 A
  	LO V5 S
  	LO V1
  	Set2	caGcTGGaATTcTTtCTaa	6286	tTaGAAaGAaTTcCAGCtg	6454	1527
  	1545 A
  	LO V5 S
  	LO V1
  	Set2	gaCtACCaGTTgTGgTTaa	6287	tTaACCaCAaCTgGTAGtc	6455	1737
  	1755 A
  	LO V5 S
  	LO V1
  	Set2 254	ccAtAcAActGttttGAAA	6288	tTTcAAAAcAGTTGtATGG	6456	236
  	A48 S26
  	Set2 703	GAttAActAtcAAGAtGAt	6289	aTcATCTTGAtAGTtAATC	6457	685
  	A48 S26
  	Set2 709	ctAtcAAGAtGAtGcAGAA	6290	tTCTGcATcATCTTGAtAG	6458	691
  	A48 S26
  	Set2 895	GAAtAcAAAtGAtGtAGAA	6291	tTCtAcATcATTTGtATTC	6459	877
  	A48 S26
  	Set2	tGttGGAttGAttcGAAAt	6292	aTTTCGAATcAATCcAAcA	6460	1798
  	1816 A48
  	S26
  	Set2	GGGtccGcAtGGAAGAAAt	6293	aTTTCTTCcATGCGGACCC	6461	1956
  	1974 A48
  	S26
  	Set2	tcctAGctAtcGttctttt	6294	aAAAGAACGAtAGCtAGGA	6462	2407
  	2425 A48
  	S26
  	Set2	AAGtGAAGAAtGcAcAAGA	6295	tCTTGTGcATTCTTcACTT	6463	3128
  	3146 A48
  	S26
  	Set2 889	cAtGcAGAAtAcAAAtGAt	6296	aTcATTTGtATTCTGcATG	6464	871
  	A48 S26
  	Set2	ActGttGGAttGAttcGAA	6297	tTCGAATcAATCcAAcAGT	6465	1796
  	1814 A48
  	S26
  	Set2	GAccccAAGctttAGtAAA	6298	tTtACtAAAGCTTGGGGTC	6466	1227
  	1245 A48
  	S26
  	Set2	AGccttGcttGttAAAttt	6299	aAATTtAAcAAGcAAGGCT	6467	3178
  	3196 A48
  	S26
  	Set2	ttcAGAtGctGcAActAAA	6300	tTtAGTTGcAGcATCTGAA	6468	1432
  	1450 A48
  	S26
  	Set2	AtcAcAAGAtGGAAtttAt	6301	atAAATTCcATCTTGTGAT	6469	3151
  	3169 A48
  	S26
  	Set2	AAtAGAAAAtGGtccAAtt	6302	aATTGGACcATTTTCtATT	6470	3459
  	3477 A48
  	S26
  	Set2 865	GAtGGtGtctGctAttGtA	6303	tAcAAtAGcAGAcACcATC	6471	847
  	A48 S26
  	Set2	ccAAGctttAGtAAAtAtA	6304	tAtATTtACtAAAGCTTGG	6472	1231
  	1249 A48
  	S26
  	Set2	cAAGctttAGtAAAtAtAA	6305	ttAtATTtACtAAAGCTTG	6473	1232
  	1250 A48
  	S26
  	Set2	ctctGAcAGAGttActtcA	6306	tGAAGtAAcTcTGTcAGAG	6474	2184
  	2202 A48
  	S26
  	Set2	cAGctGGAAttctttctAA	6307	ttAGAAAGAATTCcAGCTG	6475	1527
  	1545 A48
  	S26
  	Set2	GActAccAGttGtGGttAA	6308	ttAACcAcAACTGGtAGTC	6476	1737
  	1755 A48
  	S26

  		SEQ		SEQ
  		ID		ID
  Nickname	First Strand Sequence	NO:	Second Strand Sequence	NO:
  hs_CTNNB1_1816_AD26740_A22S26	uGuuGGAuuGAuucGAAAuuu	6477	AUUUCGAAUcAAUCcAAcAuu	6486
  hs_CTNNB1_3477_AD-	AAuAGAAAAuGGuccAAuuuu	6478	AAUUGGACcAUUUUCuAUUuu	6487
  26918-
  A22S26
  hs_CTNNB1_1814_AD18983_A22S26	AcuGuuGGAuuGAuucGAAuu	6479	UUCGAAUcAAUCcAAcAGUuu	6488
  hs_CTNNB1_709_AD26109_A22S26	cuAucAAGAuGAuGcAGAAuu	6480	UUCUGcAUcAUCUUGAuAGuu	6489
  hs_CTNNB1_254_AD-	ccAuAcAAcuGuuuuGAAAuu	6481	UUUcAAAAcAGUUGuAUGGuu	6490
  26034-A22S26
  hs_CTNNB1_3169_AD-	AucAcAAGAuGGAAuuuAuuu	6482	AuAAAUUCcAUCUUGUGAUuu	6491
  25944-
  A22S26
  hs_CTNNB1_703_AD-	AUcAUCUUGAuAGUuAAUCuu	6483	uccuAGcuAucGuucuuuuuu	6492
  26108-A22S26
  hs_CTNNB1_2425_AD-	uccuAGcuAucGuucuuuuuu	6484	AAAAGAACGAuAGCuAGGAuu	6493
  26800-
  A22S26
  hs_CTNNB1_1974_AD-	GGGuccGcAuGGAAGAAAuuu	6485	AUUUCUUCcAUGCGGACCCuu	6494
  26752-
  A22S26

• “Position” indicates the position of the RNAi agent in the human Beta-Catenin sequence NM_001098210.1.
• The sequences in Table 3 are represented by the abbreviations in Table 3A:

• TABLE 3A
  ABBREVIATIONS

  	Abbreviationa	Nucleotide(s)
  	A	adenosine-5′-phosphate
  	C	cytidine-5′-phosphate
  	G	guanosine-5′-phosphate
  	dT	2′-deoxy-thymidine-5′-phosphate
  	U	uridine-5′-phosphate
  	c	2′-O-methylcytidine-5′-phosphate
  	u	2′-O-methyluridine-5′-phosphate
  	sdT	2′-deoxy Thymidine 5′-phosphorothioate

• Modified and unmodified variants of the RNAi agents of Tables 1, 2 and 3 are easily conceived by one of skill in the art. Unmodified variants include those which do not comprise a modification of the base (such as provided in Table 3). In several cases, a pyrimidine in the sense strand is modified; and/or a pyrimidine preceding a “A” base in the anti-sense strand is modified. Modifications involving other positions (or the absence of a modification at a particular base) are easily conceived.
• In general, the sense strand is heavily modified, and the anti-sense strand lightly modified. Some modifications are placed at sites predicted to be sensitive to endonucleases. Some modifications are designed to eliminate an immune response to the RNAi agent while preserving activity. Some modifications serve more than one purpose.
• RNAi agents are also on occasion referenced by a “ND” prefix rather than “AD”; thus RNAi agents designated AD-18892 and ND-18892, for example, are identical and comprise the same sequence.
• Of the RNAi agents listed herein, many were synthesized, as described in Example 2, and tested in vitro, as described in Example 3.
Example 1A
• Overlapping siRNAs
• Some of the siRNAs listed above overlap each other in sequence. The following table presents a compilation of groups of RNAi agents, wherein each member of a group overlaps with each other member of the same group by at least 12 nt. A 12-nt portion of the overlap of the sense strands and a 12-nt portion of the overlap of the anti-sense strand are presented. Thus, for example, AD-26022 and AD-26204 share the common technical feature of the sequence of CCUGUUCCCCUG (SEQ ID NO: 1319) in the sense strand, and the sequence of CAGGGGAACAGG (SEQ ID NO: 2714) in the anti-sense strand. Note of course that only a 12-nt portion of the overlap is shown; many groups of RNAi agents will overlap by more than 12 nt. The position within the gene is also indicated.
• The disclosure also encompasses subgroups of the disclosed groups of overlapping RNAi agents. For example, the disclosure contemplates the group of AD-26027, AD-26024, AD-26028, AD-26026, AD-26025, which all share the sequences of SEQ ID NOs: 1334 and 2729. However, the disclosure also contemplates all subgroups or partial groups within this group, e.g., AD-26027 and AD-26024; AD-26027, AD-26024, AD-26028, and AD-26026; AD-26028, AD-26026, and AD-26025; AD-26027 and AD-26028; AD-26028 and AD-26025; etc. The disclosure thus encompasses any subgroup within a disclosed group of overlapping RNAi agents. The sequences of members of these subgroups can be combined with any other element disclosed herein (e.g., modification, sets of modification, 5′ and/or 3′ end cap(s), blunt end(s), overhang(s), ligand(s), additional treatment(s) or method(s), pharmaceutical carrier(s), additional RNAi agent(s), etc.), provided that such combinations are not mutually exclusive (e.g., a RNAi agent comprising two strands cannot by definition have both two blunt ends and two overhangs).

• TABLE 4
  Groups of overlapping RNAi agents to Beta-Catenin

  		SEQ		SEQ
  		ID	Anti-sense	ID	Overlapping groups of
  Position	Sense overlap	NO:	overlap	NO:	RNAi agents

  206	CCUGUUCCCCUG	1319	CAGGGGAACAGG	2714	AD-26022, AD-26204
  207	CUGUUCCCCUGA	1320	UCAGGGGAACAG	2715	AD-26022, AD-26204
  208	UGUUCCCCUGAG	1321	CUCAGGGGAACA	2716	AD-26022, AD-26023
  209	GUUCCCCUGAGG	1322	CCUCAGGGGAAC	2717	AD-26022, AD-26023,
  					AD-26204
  210	UUCCCCUGAGGG	1323	CCCUCAGGGGAA	2718	AD-26022, AD-26023,
  					AD-26204
  211	UCCCCUGAGGGU	1324	ACCCUCAGGGGA	2719	AD-26022, AD-26023,
  					AD-26204
  212	CCCCUGAGGGUA	1325	UACCCUCAGGGG	2720	AD-26022, AD-26023,
  					AD-26204
  213	CCCUGAGGGUAU	1326	AUACCCUCAGGG	2721	AD-26022, AD-26023
  214	CCUGAGGGUAUU	1327	AAUACCCUCAGG	2722	AD-26024, AD-26023
  215	CUGAGGGUAUUU	1328	AAAUACCCUCAG	2723	AD-26024, AD-26025
  216	UGAGGGUAUUUG	1329	CAAAUACCCUCA	2724	AD-26024, AD-26026
  217	GAGGGUAUUUGA	1330	UCAAAUACCCUC	2725	AD-26024, AD-26025
  218	AGGGUAUUUGAA	1331	UUCAAAUACCCU	2726	AD-26024, AD-26026,
  					AD-26025
  219	GGGUAUUUGAAG	1332	CUUCAAAUACCC	2727	AD-26024, AD-26026,
  					AD-26025
  220	GGUAUUUGAAGU	1333	ACUUCAAAUACC	2728	AD-26027, AD-26024,
  					AD-26026, AD-26025
  221	GUAUUUGAAGUA	1334	UACUUCAAAUAC	2729	AD-26027, AD-26024,
  					AD-26028, AD-26026,
  					AD-26025
  222	UAUUUGAAGUAU	1335	AUACUUCAAAUA	2730	AD-26027, AD-26028,
  					AD-26026, AD-26025
  223	AUUUGAAGUAUA	1336	UAUACUUCAAAU	2731	AD-26027, AD-26028
  224	UUUGAAGUAUAC	1337	GUAUACUUCAAA	2732	AD-26027, AD-26029
  225	UUGAAGUAUACC	1338	GGUAUACUUCAA	2733	AD-26029, AD-26028
  226	UGAAGUAUACCA	1339	UGGUAUACUUCA	2734	AD-26027, AD-26029,
  					AD-26028
  227	GAAGUAUACCAU	1340	AUGGUAUACUUC	2735	AD-26027, AD-26029,
  					AD-26028
  228	AAGUAUACCAUA	1341	UAUGGUAUACUU	2736	AD-26029, AD-26028
  229	AGUAUACCAUAC	1342	GUAUGGUAUACU	2737	AD-26029, AD-26030
  230	GUAUACCAUACA	1343	UGUAUGGUAUAC	2738	AD-26031, AD-26029,
  					AD-26030
  231	UAUACCAUACAA	1344	UUGUAUGGUAUA	2739	AD-26032, AD-26031,
  					AD-26029, AD-26030
  232	AUACCAUACAAC	1345	GUUGUAUGGUAU	2740	AD-26032, AD-26031
  233	UACCAUACAACU	1346	AGUUGUAUGGUA	2741	AD-26032, AD-26031,
  					AD-26030
  234	ACCAUACAACUG	1347	CAGUUGUAUGGU	2742	AD-26032, AD-26031,
  					AD-26033, AD-26030
  235	CCAUACAACUGU	1348	ACAGUUGUAUGG	2743	AD-26032, AD-26034,
  					AD-26031, AD-26033,
  					AD-26030
  236	CAUACAACUGUU	1349	AACAGUUGUAUG	2744	AD-26032, AD-26034,
  					AD-26031, AD-26033,
  					AD-26030
  237	AUACAACUGUUU	1350	AAACAGUUGUAU	2745	AD-26032, AD-26034,
  					AD-26031, AD-26033
  238	UACAACUGUUUU	1351	AAAACAGUUGUA	2746	AD-26032, AD-26034,
  					AD-26033
  239	ACAACUGUUUUG	1352	CAAAACAGUUGU	2747	AD-26034, AD-26033
  240	CAACUGUUUUGA	1353	UCAAAACAGUUG	2748	AD-26034, AD-26033
  241	AACUGUUUUGAA	1354	UUCAAAACAGUU	2749	AD-26034, AD-26033
  250	GAAAAUCCAGCG	1355	CGCUGGAUUUUC	2750	AD-19763, AD-26035
  251	AAAAUCCAGCGU	1356	ACGCUGGAUUUU	2751	AD-26036, AD-19763,
  					AD-26035
  252	AAAUCCAGCGUG	1357	CACGCUGGAUUU	2752	AD-26036, AD-19763,
  					AD-26035
  253	AAUCCAGCGUGG	1358	CCACGCUGGAUU	2753	AD-26036, AD-26035
  254	AUCCAGCGUGGA	1359	UCCACGCUGGAU	2754	AD-26036, AD-26035
  255	UCCAGCGUGGAC	1360	GUCCACGCUGGA	2755	AD-26036, AD-26035
  256	CCAGCGUGGACA	1361	UGUCCACGCUGG	2756	AD-26036, AD-26035,
  					AD-26037
  257	CAGCGUGGACAA	1362	UUGUCCACGCUG	2757	AD-26036, AD-26035,
  					AD-26037
  258	AGCGUGGACAAU	1363	AUUGUCCACGCU	2758	AD-26036, AD-26037
  261	GUGGACAAUGGC	1364	GCCAUUGUCCAC	2759	AD-26038, AD-26037
  262	UGGACAAUGGCU	1365	AGCCAUUGUCCA	2760	AD-26038, AD-26037
  263	GGACAAUGGCUA	1366	UAGCCAUUGUCC	2761	AD-26038, AD-26037
  264	GACAAUGGCUAC	1367	GUAGCCAUUGUC	2762	AD-18896, AD-26038
  265	ACAAUGGCUACU	1368	AGUAGCCAUUGU	2763	AD-18896, AD-26038,
  					AD-18953
  266	CAAUGGCUACUC	1369	GAGUAGCCAUUG	2764	AD-18896, AD-26038,
  					AD-18953
  267	AAUGGCUACUCA	1370	UGAGUAGCCAUU	2765	AD-18896, AD-26038,
  					AD-18953
  268	AUGGCUACUCAA	1371	UUGAGUAGCCAU	2766	AD-18896, AD-26038,
  					AD-18953, AD-26040
  269	UGGCUACUCAAG	1372	CUUGAGUAGCCA	2767	AD-18896, AD-26041,
  					AD-18953, AD-26040
  270	GGCUACUCAAGC	1373	GCUUGAGUAGCC	2768	AD-18896, AD-26041,
  					AD-26039, AD-18953,
  					AD-26040
  271	GCUACUCAAGCU	1374	AGCUUGAGUAGC	2769	AD-18896, AD-26041,
  					AD-18953, AD-26040
  272	CUACUCAAGCUG	1375	CAGCUUGAGUAG	2770	AD-26041, AD-26042,
  					AD-18953, AD-26040
  273	UACUCAAGCUGA	1376	UCAGCUUGAGUA	2771	AD-26041, AD-26042,
  					AD-26040
  274	ACUCAAGCUGAU	1377	AUCAGCUUGAGU	2772	AD-26041, AD-26042,
  					AD-26039, AD-26040
  275	CUCAAGCUGAUU	1378	AAUCAGCUUGAG	2773	AD-26041, AD-26042,
  					AD-26040
  276	UCAAGCUGAUUU	1379	AAAUCAGCUUGA	2774	AD-26041, AD-26042
  290	UGGAGUUGGACA	1380	UGUCCAACUCCA	2775	AD-26043, AD-26044
  291	GGAGUUGGACAU	1381	AUGUCCAACUCC	2776	AD-26043, AD-26044
  294	GUUGGACAUGGC	1382	GCCAUGUCCAAC	2777	AD-26045, AD-26044
  295	UUGGACAUGGCC	1383	GGCCAUGUCCAA	2778	AD-26045, AD-26044
  296	UGGACAUGGCCA	1384	UGGCCAUGUCCA	2779	AD-26045, AD-26044
  297	GGACAUGGCCAU	1385	AUGGCCAUGUCC	2780	AD-26045, AD-26044
  306	CAUGGAACCAGA	1386	UCUGGUUCCAUG	2781	AD-26047, AD-26046
  307	AUGGAACCAGAC	1387	GUCUGGUUCCAU	2782	AD-26047, AD-26046
  308	UGGAACCAGACA	1388	UGUCUGGUUCCA	2783	AD-26047, AD-26046
  309	GGAACCAGACAG	1389	CUGUCUGGUUCC	2784	AD-26047, AD-26046
  310	GAACCAGACAGA	1390	UCUGUCUGGUUC	2785	AD-26047, AD-26046
  311	AACCAGACAGAA	1391	UUCUGUCUGGUU	2786	AD-26047, AD-26046
  316	GACAGAAAAGCG	1392	CGCUUUUCUGUC	2787	AD-26050, AD-26049
  317	ACAGAAAAGCGG	1393	CCGCUUUUCUGU	2788	AD-26050, AD-26049
  318	CAGAAAAGCGGC	1394	GCCGCUUUUCUG	2789	AD-26050, AD-26049
  319	AGAAAAGCGGCU	1395	AGCCGCUUUUCU	2790	AD-26050, AD-26049
  320	GAAAAGCGGCUG	1396	CAGCCGCUUUUC	2791	AD-26050, AD-26049
  321	AAAAGCGGCUGU	1397	ACAGCCGCUUUU	2792	AD-26050, AD-26049
  322	AAAGCGGCUGUU	1398	AACAGCCGCUUU	2793	AD-26050, AD-26049
  323	AAGCGGCUGUUA	1399	UAACAGCCGCUU	2794	AD-26050, AD-19743
  330	UGUUAGUCACUG	1400	CAGUGACUAACA	2795	AD-26051, AD-19743
  337	CACUGGCAGCAA	1401	UUGCUGCCAGUG	2796	AD-26051, AD-26052
  338	ACUGGCAGCAAC	1402	GUUGCUGCCAGU	2797	AD-26053, AD-26052
  339	CUGGCAGCAACA	1403	UGUUGCUGCCAG	2798	AD-26053, AD-26052
  340	UGGCAGCAACAG	1404	CUGUUGCUGCCA	2799	AD-26053, AD-26052
  341	GGCAGCAACAGU	1405	ACUGUUGCUGCC	2800	AD-26053, AD-26052
  342	GCAGCAACAGUC	1406	GACUGUUGCUGC	2801	AD-26053, AD-26052
  343	CAGCAACAGUCU	1407	AGACUGUUGCUG	2802	AD-26053, AD-26052
  344	AGCAACAGUCUU	1408	AAGACUGUUGCU	2803	AD-26053, AD-26052
  353	CUUACCUGGACU	1409	AGUCCAGGUAAG	2804	AD-26054, AD-26055
  354	UUACCUGGACUC	1410	GAGUCCAGGUAA	2805	AD-26054, AD-26055
  355	UACCUGGACUCU	1411	AGAGUCCAGGUA	2806	AD-26054, AD-26055
  356	ACCUGGACUCUG	1412	CAGAGUCCAGGU	2807	AD-26054, AD-26055
  357	CCUGGACUCUGG	1413	CCAGAGUCCAGG	2808	AD-26056, AD-26055
  358	CUGGACUCUGGA	1414	UCCAGAGUCCAG	2809	AD-26054, AD-26056,
  					AD-26055
  359	UGGACUCUGGAA	1415	UUCCAGAGUCCA	2810	AD-26054, AD-26056,
  					AD-26055
  360	GGACUCUGGAAU	1416	AUUCCAGAGUCC	2811	AD-26056, AD-26055
  366	UGGAAUCCAUUC	1417	GAAUGGAUUCCA	2812	AD-19072, AD-18925
  367	GGAAUCCAUUCU	1418	AGAAUGGAUUCC	2813	AD-19072, AD-18925
  368	GAAUCCAUUCUG	1419	CAGAAUGGAUUC	2814	AD-19072, AD-18925
  369	AAUCCAUUCUGG	1420	CCAGAAUGGAUU	2815	AD-19072, AD-18925
  370	AUCCAUUCUGGU	1421	ACCAGAAUGGAU	2816	AD-19072, AD-18925
  371	UCCAUUCUGGUG	1422	CACCAGAAUGGA	2817	AD-19072, AD-18925
  372	CCAUUCUGGUGC	1423	GCACCAGAAUGG	2818	AD-19072, AD-18925
  401	CUCUGAGUGGUA	1424	UACCACUCAGAG	2819	AD-26060, AD-26059
  402	UCUGAGUGGUAA	1425	UUACCACUCAGA	2820	AD-26060, AD-26059
  403	CUGAGUGGUAAA	1426	UUUACCACUCAG	2821	AD-26060, AD-26059
  417	CAAUCCUGAGGA	1427	UCCUCAGGAUUG	2822	AD-26062, AD-26061
  418	AAUCCUGAGGAA	1428	UUCCUCAGGAUU	2823	AD-26062, AD-26061
  423	UGAGGAAGAGGA	1429	UCCUCUUCCUCA	2824	AD-26062, AD-26063
  424	GAGGAAGAGGAU	1430	AUCCUCUUCCUC	2825	AD-26062, AD-26063
  441	UACCUCCCAAGU	1431	ACUUGGGAGGUA	2826	AD-26065, AD-26064
  442	ACCUCCCAAGUC	1432	GACUUGGGAGGU	2827	AD-26065, AD-26064
  443	CCUCCCAAGUCC	1433	GGACUUGGGAGG	2828	AD-26065, AD-26064
  444	CUCCCAAGUCCU	1434	AGGACUUGGGAG	2829	AD-26065, AD-26064
  445	UCCCAAGUCCUG	1435	CAGGACUUGGGA	2830	AD-26065, AD-26064
  446	CCCAAGUCCUGU	1436	ACAGGACUUGGG	2831	AD-26065, AD-26064
  447	CCAAGUCCUGUA	1437	UACAGGACUUGG	2832	AD-26065, AD-26064
  457	UAUGAGUGGGAA	1438	UUCCCACUCAUA	2833	AD-26066, AD-26067
  459	UGAGUGGGAACA	1439	UGUUCCCACUCA	2834	AD-26070, AD-26067
  460	GAGUGGGAACAG	1440	CUGUUCCCACUC	2835	AD-26071, AD-26070,
  					AD-26067
  461	AGUGGGAACAGG	1441	CCUGUUCCCACU	2836	AD-26071, AD-26070,
  					AD-26067
  462	GUGGGAACAGGG	1442	CCCUGUUCCCAC	2837	AD-26071, AD-26070,
  					AD-26067
  463	UGGGAACAGGGA	1443	UCCCUGUUCCCA	2838	AD-26071, AD-26070,
  					AD-26067
  464	GGGAACAGGGAU	1444	AUCCCUGUUCCC	2839	AD-26071, AD-26070,
  					AD-26067
  465	GGAACAGGGAUU	1445	AAUCCCUGUUCC	2840	AD-26071, AD-26070
  466	GAACAGGGAUUU	1446	AAAUCCCUGUUC	2841	AD-26071, AD-26070
  477	UUCUCAGUCCUU	1447	AAGGACUGAGAA	2842	AD-26073, AD-26072
  480	UCAGUCCUUCAC	1448	GUGAAGGACUGA	2843	AD-26074, AD-26073
  481	CAGUCCUUCACU	1449	AGUGAAGGACUG	2844	AD-26074, AD-26073
  482	AGUCCUUCACUC	1450	GAGUGAAGGACU	2845	AD-26074, AD-26073
  483	GUCCUUCACUCA	1451	UGAGUGAAGGAC	2846	AD-26074, AD-26073
  484	UCCUUCACUCAA	1452	UUGAGUGAAGGA	2847	AD-26074, AD-26073
  486	CUUCACUCAAGA	1453	UCUUGAGUGAAG	2848	AD-26074, AD-26075
  487	UUCACUCAAGAA	1454	UUCUUGAGUGAA	2849	AD-26074, AD-26075
  492	UCAAGAACAAGU	1455	ACUUGUUCUUGA	2850	AD-26076, AD-26075
  493	CAAGAACAAGUA	1456	UACUUGUUCUUG	2851	AD-26076, AD-26075
  511	AUUGAUGGACAG	1457	CUGUCCAUCAAU	2852	AD-26077, AD-26078
  512	UUGAUGGACAGU	1458	ACUGUCCAUCAA	2853	AD-26077, AD-26078
  513	UGAUGGACAGUA	1459	UACUGUCCAUCA	2854	AD-26077, AD-26078
  523	UAUGCAAUGACU	1460	AGUCAUUGCAUA	2855	AD-19757, AD-19756
  524	AUGCAAUGACUC	1461	GAGUCAUUGCAU	2856	AD-19757, AD-19756
  525	UGCAAUGACUCG	1462	CGAGUCAUUGCA	2857	AD-19757, AD-19756
  526	GCAAUGACUCGA	1463	UCGAGUCAUUGC	2858	AD-19757, AD-19756
  534	UCGAGCUCAGAG	1464	CUCUGAGCUCGA	2859	AD-19744, AD-26079
  535	CGAGCUCAGAGG	1465	CCUCUGAGCUCG	2860	AD-19744, AD-26079
  536	GAGCUCAGAGGG	1466	CCCUCUGAGCUC	2861	AD-19744, AD-26079
  537	AGCUCAGAGGGU	1467	ACCCUCUGAGCU	2862	AD-19744, AD-26079
  538	GCUCAGAGGGUA	1468	UACCCUCUGAGC	2863	AD-19744, AD-26079
  541	CAGAGGGUACGA	1469	UCGUACCCUCUG	2864	AD-26080, AD-19744
  542	AGAGGGUACGAG	1470	CUCGUACCCUCU	2865	AD-26080, AD-26081
  543	GAGGGUACGAGC	1471	GCUCGUACCCUC	2866	AD-26080, AD-26081
  544	AGGGUACGAGCU	1472	AGCUCGUACCCU	2867	AD-26080, AD-26081
  545	GGGUACGAGCUG	1473	CAGCUCGUACCC	2868	AD-26080, AD-26081
  546	GGUACGAGCUGC	1474	GCAGCUCGUACC	2869	AD-26080, AD-26082
  547	GUACGAGCUGCU	1475	AGCAGCUCGUAC	2870	AD-26080, AD-26081,
  					AD-26082
  548	UACGAGCUGCUA	1476	UAGCAGCUCGUA	2871	AD-26080, AD-26081,
  					AD-26082
  549	ACGAGCUGCUAU	1477	AUAGCAGCUCGU	2872	AD-26081, AD-26082
  558	UAUGUUCCCUGA	1478	UCAGGGAACAUA	2873	AD-26084, AD-26083
  559	AUGUUCCCUGAG	1479	CUCAGGGAACAU	2874	AD-26084, AD-26083
  560	UGUUCCCUGAGA	1480	UCUCAGGGAACA	2875	AD-26084, AD-26083
  561	GUUCCCUGAGAC	1481	GUCUCAGGGAAC	2876	AD-26084, AD-26085,
  					AD-26083
  562	UUCCCUGAGACA	1482	UGUCUCAGGGAA	2877	AD-26084, AD-26085,
  					AD-26083
  563	UCCCUGAGACAU	1483	AUGUCUCAGGGA	2878	AD-26084, AD-26085,
  					AD-26083
  564	CCCUGAGACAUU	1484	AAUGUCUCAGGG	2879	AD-26084, AD-26085,
  					AD-26083
  565	CCUGAGACAUUA	1485	UAAUGUCUCAGG	2880	AD-26084, AD-26085
  576	AGAUGAGGGCAU	1486	AUGCCCUCAUCU	2881	AD-26086, AD-18911
  577	GAUGAGGGCAUG	1487	CAUGCCCUCAUC	2882	AD-26086, AD-18911
  578	AUGAGGGCAUGC	1488	GCAUGCCCUCAU	2883	AD-19011, AD-18911
  579	UGAGGGCAUGCA	1489	UGCAUGCCCUCA	2884	AD-26086, AD-19011,
  					AD-18911
  580	GAGGGCAUGCAG	1490	CUGCAUGCCCUC	2885	AD-18911, AD-26087
  581	AGGGCAUGCAGA	1491	UCUGCAUGCCCU	2886	AD-18959, AD-26086,
  					AD-18911, AD-26087
  582	GGGCAUGCAGAU	1492	AUCUGCAUGCCC	2887	AD-18911, AD-26087
  583	GGCAUGCAGAUC	1493	GAUCUGCAUGCC	2888	AD-26088, AD-18911,
  					AD-26087
  584	GCAUGCAGAUCC	1494	GGAUCUGCAUGC	2889	AD-26088, AD-26087
  585	CAUGCAGAUCCC	1495	GGGAUCUGCAUG	2890	AD-26088, AD-18959,
  					AD-19011, AD-26087
  586	AUGCAGAUCCCA	1496	UGGGAUCUGCAU	2891	AD-26088, AD-26087
  587	UGCAGAUCCCAU	1497	AUGGGAUCUGCA	2892	AD-26088, AD-18959
  588	GCAGAUCCCAUC	1498	GAUGGGAUCUGC	2893	AD-26088, AD-18959
  590	AGAUCCCAUCUA	1499	UAGAUGGGAUCU	2894	AD-26088, AD-26089
  594	CCCAUCUACACA	1500	UGUGUAGAUGGG	2895	AD-26089, AD-26090
  595	CCAUCUACACAG	1501	CUGUGUAGAUGG	2896	AD-26089, AD-26090
  596	CAUCUACACAGU	1502	ACUGUGUAGAUG	2897	AD-26089, AD-26090
  597	AUCUACACAGUU	1503	AACUGUGUAGAU	2898	AD-26089, AD-26090
  610	GAUGCUGCUCAU	1504	AUGAGCAGCAUC	2899	AD-26091, AD-26092
  611	AUGCUGCUCAUC	1505	GAUGAGCAGCAU	2900	AD-26092, AD-26093
  612	UGCUGCUCAUCC	1506	GGAUGAGCAGCA	2901	AD-26092, AD-26094
  613	GCUGCUCAUCCC	1507	GGGAUGAGCAGC	2902	AD-26092, AD-26093
  614	CUGCUCAUCCCA	1508	UGGGAUGAGCAG	2903	AD-26092, AD-26093,
  					AD-26094
  615	UGCUCAUCCCAC	1509	GUGGGAUGAGCA	2904	AD-26092, AD-26093,
  					AD-26094
  616	GCUCAUCCCACU	1510	AGUGGGAUGAGC	2905	AD-26092, AD-26093,
  					AD-26094
  617	CUCAUCCCACUA	1511	UAGUGGGAUGAG	2906	AD-26092, AD-26094
  618	UCAUCCCACUAA	1512	UUAGUGGGAUGA	2907	AD-19070, AD-18949,
  					AD-26093, AD-26094
  619	CAUCCCACUAAU	1513	AUUAGUGGGAUG	2908	AD-18949, AD-19048,
  					AD-18954, AD-26094
  620	AUCCCACUAAUG	1514	CAUUAGUGGGAU	2909	AD-19070, AD-18918,
  					AD-19048, AD-18954
  621	UCCCACUAAUGU	1515	ACAUUAGUGGGA	2910	AD-19070, AD-18949,
  					AD-18918, AD-19048,
  					AD-18954
  622	CCCACUAAUGUC	1516	GACAUUAGUGGG	2911	AD-26095, AD-19070,
  					AD-18918, AD-19048,
  					AD-18954
  623	CCACUAAUGUCC	1517	GGACAUUAGUGG	2912	AD-26095, AD-18949,
  					AD-18918, AD-19048,
  					AD-18954
  624	CACUAAUGUCCA	1518	UGGACAUUAGUG	2913	AD-26095, AD-18949,
  					AD-18918, AD-19048,
  					AD-18954
  625	ACUAAUGUCCAG	1519	CUGGACAUUAGU	2914	AD-26095, AD-18918,
  					AD-19048
  626	CUAAUGUCCAGC	1520	GCUGGACAUUAG	2915	AD-26095, AD-18918,
  					AD-19048
  627	UAAUGUCCAGCG	1521	CGCUGGACAUUA	2916	AD-26095, AD-18918
  636	GCGUUUGGCUGA	1522	UCAGCCAAACGC	2917	AD-26096, AD-19765
  637	CGUUUGGCUGAA	1523	UUCAGCCAAACG	2918	AD-26096, AD-19765
  638	GUUUGGCUGAAC	1524	GUUCAGCCAAAC	2919	AD-26096, AD-19765
  639	UUUGGCUGAACC	1525	GGUUCAGCCAAA	2920	AD-26096, AD-19765
  640	UUGGCUGAACCA	1526	UGGUUCAGCCAA	2921	AD-26096, AD-18974,
  					AD-19765
  641	UGGCUGAACCAU	1527	AUGGUUCAGCCA	2922	AD-26096, AD-19765,
  					AD-26097
  642	GGCUGAACCAUC	1528	GAUGGUUCAGCC	2923	AD-18974, AD-19000,
  					AD-19765, AD-26097
  643	GCUGAACCAUCA	1529	UGAUGGUUCAGC	2924	AD-18974, AD-19765,
  					AD-26097
  644	CUGAACCAUCAC	1530	GUGAUGGUUCAG	2925	AD-18974, AD-19000
  645	UGAACCAUCACA	1531	UGUGAUGGUUCA	2926	AD-18974, AD-26097
  646	GAACCAUCACAG	1532	CUGUGAUGGUUC	2927	AD-18974, AD-19000,
  					AD-26097
  647	AACCAUCACAGA	1533	UCUGUGAUGGUU	2928	AD-18974, AD-19000,
  					AD-26098, AD-26097
  648	ACCAUCACAGAU	1534	AUCUGUGAUGGU	2929	AD-19000, AD-26098,
  					AD-26099, AD-26097
  649	CCAUCACAGAUG	1535	CAUCUGUGAUGG	2930	AD-19000, AD-26098,
  					AD-26099
  650	CAUCACAGAUGC	1536	GCAUCUGUGAUG	2931	AD-26098, AD-26099
  651	AUCACAGAUGCU	1537	AGCAUCUGUGAU	2932	AD-26100, AD-26098
  652	UCACAGAUGCUG	1538	CAGCAUCUGUGA	2933	AD-26100, AD-26099
  653	CACAGAUGCUGA	1539	UCAGCAUCUGUG	2934	AD-26100, AD-26098,
  					AD-26099
  654	ACAGAUGCUGAA	1540	UUCAGCAUCUGU	2935	AD-26100, AD-26099
  655	CAGAUGCUGAAA	1541	UUUCAGCAUCUG	2936	AD-26100, AD-26099
  657	GAUGCUGAAACA	1542	UGUUUCAGCAUC	2937	AD-26100, AD-26101
  658	AUGCUGAAACAU	1543	AUGUUUCAGCAU	2938	AD-26100, AD-26101
  661	CUGAAACAUGCA	1544	UGCAUGUUUCAG	2939	AD-26101, AD-26102
  662	UGAAACAUGCAG	1545	CUGCAUGUUUCA	2940	AD-26101, AD-26102
  663	GAAACAUGCAGU	1546	ACUGCAUGUUUC	2941	AD-26101, AD-26102
  664	AAACAUGCAGUU	1547	AACUGCAUGUUU	2942	AD-26101, AD-26102
  665	AACAUGCAGUUG	1548	CAACUGCAUGUU	2943	AD-26103, AD-26102
  666	ACAUGCAGUUGU	1549	ACAACUGCAUGU	2944	AD-26103, AD-26102
  667	CAUGCAGUUGUA	1550	UACAACUGCAUG	2945	AD-26103, AD-26102
  668	AUGCAGUUGUAA	1551	UUACAACUGCAU	2946	AD-26104, AD-26103,
  					AD-26102
  669	UGCAGUUGUAAA	1552	UUUACAACUGCA	2947	AD-26105, AD-26103
  670	GCAGUUGUAAAC	1553	GUUUACAACUGC	2948	AD-26105, AD-26104,
  					AD-26103
  671	CAGUUGUAAACU	1554	AGUUUACAACUG	2949	AD-26105, AD-26104,
  					AD-26103, AD-26106
  672	AGUUGUAAACUU	1555	AAGUUUACAACU	2950	AD-26105, AD-26103,
  					AD-26106
  673	GUUGUAAACUUG	1556	CAAGUUUACAAC	2951	AD-26105, AD-26104,
  					AD-26106
  674	UUGUAAACUUGA	1557	UCAAGUUUACAA	2952	AD-26105, AD-26808,
  					AD-26104, AD-26106
  675	UGUAAACUUGAU	1558	AUCAAGUUUACA	2953	AD-26105, AD-26808,
  					AD-26104, AD-26106,
  					AD-26809
  676	GUAAACUUGAUU	1559	AAUCAAGUUUAC	2954	AD-26105, AD-26808,
  					AD-26106, AD-26809
  677	UAAACUUGAUUA	1560	UAAUCAAGUUUA	2955	AD-26808, AD-26106,
  					AD-26809
  678	AAACUUGAUUAA	1561	UUAAUCAAGUUU	2956	AD-26808, AD-26810,
  					AD-26106, AD-26809
  679	AACUUGAUUAAC	1562	GUUAAUCAAGUU	2957	AD-26808, AD-26810,
  					AD-26809
  680	ACUUGAUUAACU	1563	AGUUAAUCAAGU	2958	AD-26808, AD-26809
  681	CUUGAUUAACUA	1564	UAGUUAAUCAAG	2959	AD-26107, AD-26808,
  					AD-26810, AD-26809
  682	UUGAUUAACUAU	1565	AUAGUUAAUCAA	2960	AD-26107, AD-26810,
  					AD-26809
  683	UGAUUAACUAUC	1566	GAUAGUUAAUCA	2961	AD-26107, AD-26810
  684	GAUUAACUAUCA	1567	UGAUAGUUAAUC	2962	AD-26107, AD-26810,
  					AD-26108
  685	AUUAACUAUCAA	1568	UUGAUAGUUAAU	2963	AD-26107, AD-26108
  686	UUAACUAUCAAG	1569	CUUGAUAGUUAA	2964	AD-26107, AD-26108
  687	UAACUAUCAAGA	1570	UCUUGAUAGUUA	2965	AD-26107, AD-26108
  688	AACUAUCAAGAU	1571	AUCUUGAUAGUU	2966	AD-26107, AD-26108
  690	CUAUCAAGAUGA	1572	UCAUCUUGAUAG	2967	AD-26109, AD-26108
  691	UAUCAAGAUGAU	1573	AUCAUCUUGAUA	2968	AD-26109, AD-26108
  707	AACUUGCCACAC	1574	GUGUGGCAAGUU	2969	AD-26110, AD-26111
  708	ACUUGCCACACG	1575	CGUGUGGCAAGU	2970	AD-26110, AD-26111
  709	CUUGCCACACGU	1576	ACGUGUGGCAAG	2971	AD-26110, AD-26111
  710	UUGCCACACGUG	1577	CACGUGUGGCAA	2972	AD-26110, AD-26111
  711	UGCCACACGUGC	1578	GCACGUGUGGCA	2973	AD-26110, AD-26111
  712	GCCACACGUGCA	1579	UGCACGUGUGGC	2974	AD-26110, AD-26111
  713	CCACACGUGCAA	1580	UUGCACGUGUGG	2975	AD-26110, AD-26111
  714	CACACGUGCAAU	1581	AUUGCACGUGUG	2976	AD-26112, AD-26111
  721	GCAAUCCCUGAA	1582	UUCAGGGAUUGC	2977	AD-26112, AD-26123
  722	CAAUCCCUGAAC	1583	GUUCAGGGAUUG	2978	AD-26124, AD-26123
  723	AAUCCCUGAACU	1584	AGUUCAGGGAUU	2979	AD-26124, AD-26125
  724	AUCCCUGAACUG	1585	CAGUUCAGGGAU	2980	AD-26124, AD-26123
  725	UCCCUGAACUGA	1586	UCAGUUCAGGGA	2981	AD-26124, AD-26125
  726	CCCUGAACUGAC	1587	GUCAGUUCAGGG	2982	AD-26124, AD-26123
  727	CCUGAACUGACA	1588	UGUCAGUUCAGG	2983	AD-26124, AD-26123,
  					AD-26125
  728	CUGAACUGACAA	1589	UUGUCAGUUCAG	2984	AD-26124, AD-26123,
  					AD-26125
  729	UGAACUGACAAA	1590	UUUGUCAGUUCA	2985	AD-26124, AD-26125,
  					AD-26126
  730	GAACUGACAAAA	1591	UUUUGUCAGUUC	2986	AD-26125, AD-26126
  731	AACUGACAAAAC	1592	GUUUUGUCAGUU	2987	AD-26128, AD-26126,
  					AD-26127
  732	ACUGACAAAACU	1593	AGUUUUGUCAGU	2988	AD-26128, AD-26126,
  					AD-26129
  733	CUGACAAAACUG	1594	CAGUUUUGUCAG	2989	AD-26128, AD-26126,
  					AD-26129
  734	UGACAAAACUGC	1595	GCAGUUUUGUCA	2990	AD-26128, AD-26127,
  					AD-26129
  735	GACAAAACUGCU	1596	AGCAGUUUUGUC	2991	AD-26128, AD-26126,
  					AD-26129
  736	ACAAAACUGCUA	1597	UAGCAGUUUUGU	2992	AD-26128, AD-26126,
  					AD-26127, AD-26129
  737	CAAAACUGCUAA	1598	UUAGCAGUUUUG	2993	AD-26128, AD-26127,
  					AD-26129
  738	AAAACUGCUAAA	1599	UUUAGCAGUUUU	2994	AD-26128, AD-26129
  755	AGGACCAGGUGG	1600	CCACCUGGUCCU	2995	AD-26131, AD-26130
  756	GGACCAGGUGGU	1601	ACCACCUGGUCC	2996	AD-26132, AD-26131,
  					AD-26130
  757	GACCAGGUGGUG	1602	CACCACCUGGUC	2997	AD-26132, AD-26133,
  					AD-26131, AD-26130
  758	ACCAGGUGGUGG	1603	CCACCACCUGGU	2998	AD-26132, AD-26133,
  					AD-26131, AD-26130,
  					AD-26136
  759	CCAGGUGGUGGU	1604	ACCACCACCUGG	2999	AD-26132, AD-26131,
  					AD-26136
  760	CAGGUGGUGGUU	1605	AACCACCACCUG	3000	AD-26132, AD-26133,
  					AD-26131, AD-26136
  761	AGGUGGUGGUUA	1606	UAACCACCACCU	3001	AD-26132, AD-26131,
  					AD-26130, AD-26136
  762	GGUGGUGGUUAA	1607	UUAACCACCACC	3002	AD-26132, AD-26131
  763	GUGGUGGUUAAU	1608	AUUAACCACCAC	3003	AD-26132, AD-26133,
  					AD-26136
  764	UGGUGGUUAAUA	1609	UAUUAACCACCA	3004	AD-26133, AD-26136
  784	GUUAUGGUCCAU	1610	AUGGACCAUAAC	3005	AD-26138, AD-26137
  787	AUGGUCCAUCAG	1611	CUGAUGGACCAU	3006	AD-26138, AD-26139
  788	UGGUCCAUCAGC	1612	GCUGAUGGACCA	3007	AD-26138, AD-26139,
  					AD-26140
  789	GGUCCAUCAGCU	1613	AGCUGAUGGACC	3008	AD-26142, AD-26140
  790	GUCCAUCAGCUU	1614	AAGCUGAUGGAC	3009	AD-26143, AD-26142,
  					AD-26140
  791	UCCAUCAGCUUU	1615	AAAGCUGAUGGA	3010	AD-26139, AD-26143,
  					AD-26142, AD-26140
  792	CCAUCAGCUUUC	1616	GAAAGCUGAUGG	3011	AD-26143, AD-26142,
  					AD-26140
  793	CAUCAGCUUUCU	1617	AGAAAGCUGAUG	3012	AD-26139, AD-26143,
  					AD-26142, AD-26140
  794	AUCAGCUUUCUA	1618	UAGAAAGCUGAU	3013	AD-26143, AD-26142,
  					AD-26140
  795	UCAGCUUUCUAA	1619	UUAGAAAGCUGA	3014	AD-26143, AD-26142
  796	CAGCUUUCUAAA	1620	UUUAGAAAGCUG	3015	AD-26143, AD-26142
  811	GAAGCUUCCAGA	1621	UCUGGAAGCUUC	3016	AD-26144, AD-18950
  812	AAGCUUCCAGAC	1622	GUCUGGAAGCUU	3017	AD-26144, AD-18950
  813	AGCUUCCAGACA	1623	UGUCUGGAAGCU	3018	AD-26145, AD-26144,
  					AD-18950
  814	GCUUCCAGACAC	1624	GUGUCUGGAAGC	3019	AD-26145, AD-26144
  815	CUUCCAGACACG	1625	CGUGUCUGGAAG	3020	AD-26145, AD-26144
  816	UUCCAGACACGC	1626	GCGUGUCUGGAA	3021	AD-26146, AD-26144
  817	UCCAGACACGCU	1627	AGCGUGUCUGGA	3022	AD-26145, AD-26146,
  					AD-26144
  818	CCAGACACGCUA	1628	UAGCGUGUCUGG	3023	AD-26145, AD-26146
  819	CAGACACGCUAU	1629	AUAGCGUGUCUG	3024	AD-26145, AD-26146
  820	AGACACGCUAUC	1630	GAUAGCGUGUCU	3025	AD-26146, AD-26147
  821	GACACGCUAUCA	1631	UGAUAGCGUGUC	3026	AD-19745, AD-26146
  822	ACACGCUAUCAU	1632	AUGAUAGCGUGU	3027	AD-19745, AD-26146,
  					AD-26147
  823	CACGCUAUCAUG	1633	CAUGAUAGCGUG	3028	AD-19745, AD-26147
  824	ACGCUAUCAUGC	1634	GCAUGAUAGCGU	3029	AD-19745, AD-19739,
  					AD-26147
  825	CGCUAUCAUGCG	1635	CGCAUGAUAGCG	3030	AD-19745, AD-19746,
  					AD-19739
  826	GCUAUCAUGCGU	1636	ACGCAUGAUAGC	3031	AD-19766, AD-19739,
  					AD-26147
  827	CUAUCAUGCGUU	1637	AACGCAUGAUAG	3032	AD-19766, AD-19745,
  					AD-19739, AD-26147
  828	UAUCAUGCGUUC	1638	GAACGCAUGAUA	3033	AD-19766, AD-19745,
  					AD-19739
  829	AUCAUGCGUUCU	1639	AGAACGCAUGAU	3034	AD-19766, AD-19746,
  					AD-19739
  830	UCAUGCGUUCUC	1640	GAGAACGCAUGA	3035	AD-19739, AD-26148
  831	CAUGCGUUCUCC	1641	GGAGAACGCAUG	3036	AD-19739, AD-26148
  832	AUGCGUUCUCCU	1642	AGGAGAACGCAU	3037	AD-19746, AD-26148
  842	CUCAGAUGGUGU	1643	ACACCAUCUGAG	3038	AD-26150, AD-26149
  843	UCAGAUGGUGUC	1644	GACACCAUCUGA	3039	AD-26150, AD-26149
  844	CAGAUGGUGUCU	1645	AGACACCAUCUG	3040	AD-26150, AD-26149
  845	AGAUGGUGUCUG	1646	CAGACACCAUCU	3041	AD-26150, AD-26149
  846	GAUGGUGUCUGC	1647	GCAGACACCAUC	3042	AD-26150, AD-26149
  847	AUGGUGUCUGCU	1648	AGCAGACACCAU	3043	AD-26150, AD-26149
  848	UGGUGUCUGCUA	1649	UAGCAGACACCA	3044	AD-26150, AD-26149
  854	CUGCUAUUGUAC	1650	GUACAAUAGCAG	3045	AD-26151, AD-26152
  855	UGCUAUUGUACG	1651	CGUACAAUAGCA	3046	AD-26151, AD-26152
  856	GCUAUUGUACGU	1652	ACGUACAAUAGC	3047	AD-26151, AD-26152
  857	CUAUUGUACGUA	1653	UACGUACAAUAG	3048	AD-26151, AD-26152
  860	UUGUACGUACCA	1654	UGGUACGUACAA	3049	AD-26153, AD-26152
  861	UGUACGUACCAU	1655	AUGGUACGUACA	3050	AD-26154, AD-26153,
  					AD-26152
  862	GUACGUACCAUG	1656	CAUGGUACGUAC	3051	AD-26154, AD-26153
  863	UACGUACCAUGC	1657	GCAUGGUACGUA	3052	AD-26154, AD-26153
  864	ACGUACCAUGCA	1658	UGCAUGGUACGU	3053	AD-26154, AD-26153
  865	CGUACCAUGCAG	1659	CUGCAUGGUACG	3054	AD-26154, AD-26153
  866	GUACCAUGCAGA	1660	UCUGCAUGGUAC	3055	AD-26154, AD-26155
  867	UACCAUGCAGAA	1661	UUCUGCAUGGUA	3056	AD-26154, AD-26155,
  					AD-26153
  868	ACCAUGCAGAAU	1662	AUUCUGCAUGGU	3057	AD-26154, AD-26155
  870	CAUGCAGAAUAC	1663	GUAUUCUGCAUG	3058	AD-26155, AD-26156
  871	AUGCAGAAUACA	1664	UGUAUUCUGCAU	3059	AD-26155, AD-26156
  872	UGCAGAAUACAA	1665	UUGUAUUCUGCA	3060	AD-26155, AD-26156
  873	GCAGAAUACAAA	1666	UUUGUAUUCUGC	3061	AD-26156, AD-26157
  874	CAGAAUACAAAU	1667	AUUUGUAUUCUG	3062	AD-19068, AD-26157
  875	AGAAUACAAAUG	1668	CAUUUGUAUUCU	3063	AD-19068, AD-26156
  876	GAAUACAAAUGA	1669	UCAUUUGUAUUC	3064	AD-19068, AD-26156,
  					AD-26157
  877	AAUACAAAUGAU	1670	AUCAUUUGUAUU	3065	AD-19068, AD-26158,
  					AD-26826, AD-26157
  878	AUACAAAUGAUG	1671	CAUCAUUUGUAU	3066	AD-19068, AD-26158,
  					AD-26157
  879	UACAAAUGAUGU	1672	ACAUCAUUUGUA	3067	AD-26158, AD-26826,
  					AD-26157
  880	ACAAAUGAUGUA	1673	UACAUCAUUUGU	3068	AD-19068, AD-26158,
  					AD-26826, AD-26157
  881	CAAAUGAUGUAG	1674	CUACAUCAUUUG	3069	AD-19068, AD-26158,
  					AD-26826
  882	AAAUGAUGUAGA	1675	UCUACAUCAUUU	3070	AD-26158, AD-26826
  883	AAUGAUGUAGAA	1676	UUCUACAUCAUU	3071	AD-26158, AD-26826
  906	UACCGCUGGGAC	1677	GUCCCAGCGGUA	3072	AD-26161, AD-26160
  907	ACCGCUGGGACC	1678	GGUCCCAGCGGU	3073	AD-26161, AD-26160
  908	CCGCUGGGACCU	1679	AGGUCCCAGCGG	3074	AD-26161, AD-26162
  909	CGCUGGGACCUU	1680	AAGGUCCCAGCG	3075	AD-26162, AD-26160
  910	GCUGGGACCUUG	1681	CAAGGUCCCAGC	3076	AD-26161, AD-26162
  911	CUGGGACCUUGC	1682	GCAAGGUCCCAG	3077	AD-26161, AD-26162
  912	UGGGACCUUGCA	1683	UGCAAGGUCCCA	3078	AD-26161, AD-26162,
  					AD-26163
  913	GGGACCUUGCAU	1684	AUGCAAGGUCCC	3079	AD-26161, AD-26162,
  					AD-26163, AD-26164
  914	GGACCUUGCAUA	1685	UAUGCAAGGUCC	3080	AD-26162, AD-26163,
  					AD-26164
  915	GACCUUGCAUAA	1686	UUAUGCAAGGUC	3081	AD-19759, AD-26162,
  					AD-26163, AD-26164
  916	ACCUUGCAUAAC	1687	GUUAUGCAAGGU	3082	AD-19759, AD-26163,
  					AD-26164
  917	CCUUGCAUAACC	1688	GGUUAUGCAAGG	3083	AD-19759, AD-26164
  918	CUUGCAUAACCU	1689	AGGUUAUGCAAG	3084	AD-19759, AD-26163,
  					AD-26164, AD-26165
  919	UUGCAUAACCUU	1690	AAGGUUAUGCAA	3085	AD-19759, AD-26163,
  					AD-26164, AD-26165
  920	UGCAUAACCUUU	1691	AAAGGUUAUGCA	3086	AD-19759, AD-26164,
  					AD-26165
  921	GCAUAACCUUUC	1692	GAAAGGUUAUGC	3087	AD-19759, AD-26165
  922	CAUAACCUUUCC	1693	GGAAAGGUUAUG	3088	AD-19759, AD-26165
  959	UCUUUAAGUCUG	1694	CAGACUUAAAGA	3089	AD-26166, AD-18901
  960	CUUUAAGUCUGG	1695	CCAGACUUAAAG	3090	AD-26166, AD-18901
  975	CAUUCCUGCCCU	1696	AGGGCAGGAAUG	3091	AD-26167, AD-26168
  976	AUUCCUGCCCUG	1697	CAGGGCAGGAAU	3092	AD-26167, AD-26168,
  					AD-26169
  977	UUCCUGCCCUGG	1698	CCAGGGCAGGAA	3093	AD-26170, AD-26167,
  					AD-26168, AD-26169
  978	UCCUGCCCUGGU	1699	ACCAGGGCAGGA	3094	AD-26170, AD-26168,
  					AD-26169
  979	CCUGCCCUGGUG	1700	CACCAGGGCAGG	3095	AD-26170, AD-26168
  980	CUGCCCUGGUGA	1701	UCACCAGGGCAG	3096	AD-26170, AD-26167,
  					AD-26169
  981	UGCCCUGGUGAA	1702	UUCACCAGGGCA	3097	AD-26170, AD-26167,
  					AD-26171, AD-26168,
  					AD-26169
  982	GCCCUGGUGAAA	1703	UUUCACCAGGGC	3098	AD-26170, AD-26171,
  					AD-26168, AD-26169
  983	CCCUGGUGAAAA	1704	UUUUCACCAGGG	3099	AD-26170, AD-26171,
  					AD-26169
  984	CCUGGUGAAAAU	1705	AUUUUCACCAGG	3100	AD-26170, AD-26171
  985	CUGGUGAAAAUG	1706	CAUUUUCACCAG	3101	AD-26172, AD-26171
  986	UGGUGAAAAUGC	1707	GCAUUUUCACCA	3102	AD-26172, AD-26171
  987	GGUGAAAAUGCU	1708	AGCAUUUUCACC	3103	AD-26172, AD-26171
  988	GUGAAAAUGCUU	1709	AAGCAUUUUCAC	3104	AD-26172, AD-26171
  997	CUUGGUUCACCA	1710	UGGUGAACCAAG	3105	AD-26173, AD-26174
  998	UUGGUUCACCAG	1711	CUGGUGAACCAA	3106	AD-26173, AD-26174
  999	UGGUUCACCAGU	1712	ACUGGUGAACCA	3107	AD-26173, AD-26174
  1000	GGUUCACCAGUG	1713	CACUGGUGAACC	3108	AD-26173, AD-26174
  1001	GUUCACCAGUGG	1714	CCACUGGUGAAC	3109	AD-26173, AD-26174
  1002	UUCACCAGUGGA	1715	UCCACUGGUGAA	3110	AD-26173, AD-26174
  1003	UCACCAGUGGAU	1716	AUCCACUGGUGA	3111	AD-26173, AD-26174
  1004	CACCAGUGGAUU	1717	AAUCCACUGGUG	3112	AD-26177, AD-26174
  1007	CAGUGGAUUCUG	1718	CAGAAUCCACUG	3113	AD-26177, AD-26178
  1008	AGUGGAUUCUGU	1719	ACAGAAUCCACU	3114	AD-26177, AD-26178,
  					AD-26179
  1009	GUGGAUUCUGUG	1720	CACAGAAUCCAC	3115	AD-26177, AD-26178,
  					AD-26179, AD-26180
  1010	UGGAUUCUGUGU	1721	ACACAGAAUCCA	3116	AD-26177, AD-26181,
  					AD-26178, AD-26179,
  					AD-26180
  1011	GGAUUCUGUGUU	1722	AACACAGAAUCC	3117	AD-26177, AD-26181,
  					AD-26178, AD-26179,
  					AD-26182, AD-26180
  1012	GAUUCUGUGUUG	1723	CAACACAGAAUC	3118	AD-26181, AD-26178,
  					AD-26179, AD-26182,
  					AD-26180
  1013	AUUCUGUGUUGU	1724	ACAACACAGAAU	3119	AD-26181, AD-26178,
  					AD-26179, AD-26182
  1014	UUCUGUGUUGUU	1725	AACAACACAGAA	3120	AD-26181, AD-26179,
  					AD-26182, AD-26180
  1015	UCUGUGUUGUUU	1726	AAACAACACAGA	3121	AD-26181, AD-26179,
  					AD-26182, AD-26180
  1016	CUGUGUUGUUUU	1727	AAAACAACACAG	3122	AD-26181, AD-26182,
  					AD-26180
  1017	UGUGUUGUUUUA	1728	UAAAACAACACA	3123	AD-26183, AD-26181,
  					AD-26182
  1018	GUGUUGUUUUAU	1729	AUAAAACAACAC	3124	AD-26183, AD-26182,
  					AD-26185
  1019	UGUUGUUUUAUG	1730	CAUAAAACAACA	3125	AD-26183, AD-26185
  1020	GUUGUUUUAUGC	1731	GCAUAAAACAAC	3126	AD-26183, AD-26185
  1021	UUGUUUUAUGCC	1732	GGCAUAAAACAA	3127	AD-26183, AD-26186
  1022	UGUUUUAUGCCA	1733	UGGCAUAAAACA	3128	AD-26183, AD-26185
  1023	GUUUUAUGCCAU	1734	AUGGCAUAAAAC	3129	AD-26183, AD-26185,
  					AD-26186
  1024	UUUUAUGCCAUU	1735	AAUGGCAUAAAA	3130	AD-26183, AD-26185,
  					AD-26186
  1025	UUUAUGCCAUUA	1736	UAAUGGCAUAAA	3131	AD-26185, AD-26186
  1027	UAUGCCAUUACA	1737	UGUAAUGGCAUA	3132	AD-26186, AD-19767
  1028	AUGCCAUUACAA	1738	UUGUAAUGGCAU	3133	AD-26186, AD-19767
  1031	CCAUUACAACUC	1739	GAGUUGUAAUGG	3134	AD-26187, AD-19767
  1032	CAUUACAACUCU	1740	AGAGUUGUAAUG	3135	AD-26187, AD-19767
  1033	AUUACAACUCUC	1741	GAGAGUUGUAAU	3136	AD-26187, AD-19767
  1034	UUACAACUCUCC	1742	GGAGAGUUGUAA	3137	AD-26187, AD-19767
  1035	UACAACUCUCCA	1743	UGGAGAGUUGUA	3138	AD-26188, AD-26187
  1036	ACAACUCUCCAC	1744	GUGGAGAGUUGU	3139	AD-26188, AD-26189,
  					AD-26187
  1037	CAACUCUCCACA	1745	UGUGGAGAGUUG	3140	AD-26190, AD-26188,
  					AD-26189, AD-26187
  1038	AACUCUCCACAA	1746	UUGUGGAGAGUU	3141	AD-26190, AD-26191,
  					AD-26188, AD-26189,
  					AD-26187
  1039	ACUCUCCACAAC	1747	GUUGUGGAGAGU	3142	AD-26190, AD-26192,
  					AD-26191, AD-26188,
  					AD-26189
  1040	CUCUCCACAACC	1748	GGUUGUGGAGAG	3143	AD-26190, AD-26192,
  					AD-26193, AD-26191,
  					AD-26188, AD-26189
  1041	UCUCCACAACCU	1749	AGGUUGUGGAGA	3144	AD-26190, AD-26192,
  					AD-26193, AD-26194,
  					AD-26191, AD-26188,
  					AD-26189
  1042	CUCCACAACCUU	1750	AAGGUUGUGGAG	3145	AD-26190, AD-26192,
  					AD-26193, AD-26194,
  					AD-26191, AD-26189
  1043	UCCACAACCUUU	1751	AAAGGUUGUGGA	3146	AD-26190, AD-26192,
  					AD-26193, AD-26194,
  					AD-26189
  1044	CCACAACCUUUU	1752	AAAAGGUUGUGG	3147	AD-26190, AD-26192,
  					AD-26193, AD-26194,
  					AD-26191
  1045	CACAACCUUUUA	1753	UAAAAGGUUGUG	3148	AD-26192, AD-26193,
  					AD-26194, AD-26191
  1046	ACAACCUUUUAU	1754	AUAAAAGGUUGU	3149	AD-26192, AD-26193,
  					AD-26194
  1047	CAACCUUUUAUU	1755	AAUAAAAGGUUG	3150	AD-26193, AD-26194,
  					AD-26195
  1048	AACCUUUUAUUA	1756	UAAUAAAAGGUU	3151	AD-26194, AD-26195
  1050	CCUUUUAUUACA	1757	UGUAAUAAAAGG	3152	AD-26196, AD-26195
  1051	CUUUUAUUACAU	1758	AUGUAAUAAAAG	3153	AD-26196, AD-26195
  1052	UUUUAUUACAUC	1759	GAUGUAAUAAAA	3154	AD-26196, AD-26195
  1053	UUUAUUACAUCA	1760	UGAUGUAAUAAA	3155	AD-26196, AD-26195
  1054	UUAUUACAUCAA	1761	UUGAUGUAAUAA	3156	AD-26196, AD-26195
  1057	UUACAUCAAGAA	1762	UUCUUGAUGUAA	3157	AD-26197, AD-26196
  1058	UACAUCAAGAAG	1763	CUUCUUGAUGUA	3158	AD-26198, AD-26197
  1059	ACAUCAAGAAGG	1764	CCUUCUUGAUGU	3159	AD-26198, AD-26197
  1060	CAUCAAGAAGGA	1765	UCCUUCUUGAUG	3160	AD-26198, AD-26199,
  					AD-26197
  1061	AUCAAGAAGGAG	1766	CUCCUUCUUGAU	3161	AD-26198, AD-26199,
  					AD-26197, AD-26200
  1062	UCAAGAAGGAGC	1767	GCUCCUUCUUGA	3162	AD-26198, AD-26199,
  					AD-26200
  1063	CAAGAAGGAGCU	1768	AGCUCCUUCUUG	3163	AD-26198, AD-26197,
  					AD-26200
  1064	AAGAAGGAGCUA	1769	UAGCUCCUUCUU	3164	AD-26198, AD-26199,
  					AD-26197, AD-26200
  1065	AGAAGGAGCUAA	1770	UUAGCUCCUUCU	3165	AD-26198, AD-26199,
  					AD-26200
  1066	GAAGGAGCUAAA	1771	UUUAGCUCCUUC	3166	AD-26199, AD-26200
  1067	AAGGAGCUAAAA	1772	UUUUAGCUCCUU	3167	AD-26199, AD-26200
  1068	AGGAGCUAAAAU	1773	AUUUUAGCUCCU	3168	AD-26200, AD-18977
  1072	GCUAAAAUGGCA	1774	UGCCAUUUUAGC	3169	AD-26201, AD-18977
  1073	CUAAAAUGGCAG	1775	CUGCCAUUUUAG	3170	AD-26201, AD-18977
  1074	UAAAAUGGCAGU	1776	ACUGCCAUUUUA	3171	AD-26201, AD-26202,
  					AD-18977
  1075	AAAAUGGCAGUG	1777	CACUGCCAUUUU	3172	AD-26201, AD-18977
  1076	AAAUGGCAGUGC	1778	GCACUGCCAUUU	3173	AD-26201, AD-26202
  1077	AAUGGCAGUGCG	1779	CGCACUGCCAUU	3174	AD-26201, AD-26202
  1078	AUGGCAGUGCGU	1780	ACGCACUGCCAU	3175	AD-26201, AD-26202
  1079	UGGCAGUGCGUU	1781	AACGCACUGCCA	3176	AD-26201, AD-26202
  1112	UGGUUGCCUUGC	1782	GCAAGGCAACCA	3177	AD-26205, AD-26203
  1113	GGUUGCCUUGCU	1783	AGCAAGGCAACC	3178	AD-26206, AD-26205,
  					AD-26203
  1114	GUUGCCUUGCUC	1784	GAGCAAGGCAAC	3179	AD-26206, AD-26205,
  					AD-26203, AD-26207
  1115	UUGCCUUGCUCA	1785	UGAGCAAGGCAA	3180	AD-26206, AD-26205,
  					AD-26203
  1116	UGCCUUGCUCAA	1786	UUGAGCAAGGCA	3181	AD-26206, AD-26203,
  					AD-26207
  1117	GCCUUGCUCAAC	1787	GUUGAGCAAGGC	3182	AD-26205, AD-26208,
  					AD-26207
  1118	CCUUGCUCAACA	1788	UGUUGAGCAAGG	3183	AD-26206, AD-26205,
  					AD-26208, AD-26207,
  					AD-26209
  1119	CUUGCUCAACAA	1789	UUGUUGAGCAAG	3184	AD-26206, AD-26205,
  					AD-26208, AD-26207,
  					AD-26209
  1120	UUGCUCAACAAA	1790	UUUGUUGAGCAA	3185	AD-26206, AD-26208,
  					AD-26207, AD-26209
  1121	UGCUCAACAAAA	1791	UUUUGUUGAGCA	3186	AD-26208, AD-26207,
  					AD-26209
  1122	GCUCAACAAAAC	1792	GUUUUGUUGAGC	3187	AD-26208, AD-26209
  1123	CUCAACAAAACA	1793	UGUUUUGUUGAG	3188	AD-26208, AD-26209
  1124	UCAACAAAACAA	1794	UUGUUUUGUUGA	3189	AD-26208, AD-26209
  1219	AGUGGUGGACCC	1795	GGGUCCACCACU	3190	AD-26057, AD-26213
  1220	GUGGUGGACCCC	1796	GGGGUCCACCAC	3191	AD-26057, AD-26213,
  					AD-26214
  1221	UGGUGGACCCCA	1797	UGGGGUCCACCA	3192	AD-26215, AD-26057,
  					AD-26213, AD-26214
  1222	GGUGGACCCCAA	1798	UUGGGGUCCACC	3193	AD-26215, AD-26057,
  					AD-26213
  1223	GUGGACCCCAAG	1799	CUUGGGGUCCAC	3194	AD-26215, AD-26213,
  					AD-26214
  1224	UGGACCCCAAGC	1800	GCUUGGGGUCCA	3195	AD-26215, AD-26216,
  					AD-26213, AD-26214
  1225	GGACCCCAAGCU	1801	AGCUUGGGGUCC	3196	AD-26215, AD-26217,
  					AD-26216, AD-26213,
  					AD-26214
  1226	GACCCCAAGCUU	1802	AAGCUUGGGGUC	3197	AD-26215, AD-26217,
  					AD-26216, AD-26213,
  					AD-26214, AD-26218
  1227	ACCCCAAGCUUU	1803	AAAGCUUGGGGU	3198	AD-26215, AD-26651,
  					AD-26217, AD-26216,
  					AD-26218
  1228	CCCCAAGCUUUA	1804	UAAAGCUUGGGG	3199	AD-26215, AD-26652,
  					AD-26217, AD-26216,
  					AD-26218
  1229	CCCAAGCUUUAG	1805	CUAAAGCUUGGG	3200	AD-26651, AD-26652,
  					AD-26217, AD-26216,
  					AD-26653, AD-26218
  1230	CCAAGCUUUAGU	1806	ACUAAAGCUUGG	3201	AD-26654, AD-26651,
  					AD-26652, AD-26217,
  					AD-26216, AD-26653,
  					AD-26218
  1231	CAAGCUUUAGUA	1807	UACUAAAGCUUG	3202	AD-26654, AD-26651,
  					AD-26652, AD-26217,
  					AD-26068, AD-26216,
  					AD-26653, AD-26218
  1232	AAGCUUUAGUAA	1808	UUACUAAAGCUU	3203	AD-26654, AD-26651,
  					AD-26652, AD-26217,
  					AD-26068, AD-26653,
  					AD-26069, AD-26218
  1233	AGCUUUAGUAAA	1809	UUUACUAAAGCU	3204	AD-26654, AD-26651,
  					AD-26652, AD-26068,
  					AD-26653, AD-26069,
  					AD-26218
  1234	GCUUUAGUAAAU	1810	AUUUACUAAAGC	3205	AD-26654, AD-26651,
  					AD-26652, AD-26068,
  					AD-26653, AD-26069
  1235	CUUUAGUAAAUA	1811	UAUUUACUAAAG	3206	AD-26654, AD-26652,
  					AD-26068, AD-26653,
  					AD-26069
  1236	UUUAGUAAAUAU	1812	AUAUUUACUAAA	3207	AD-26654, AD-26068,
  					AD-26653, AD-26069
  1237	UUAGUAAAUAUA	1813	UAUAUUUACUAA	3208	AD-26654, AD-26068,
  					AD-26069
  1238	UAGUAAAUAUAA	1814	UUAUAUUUACUA	3209	AD-26068, AD-26069
  1242	AAAUAUAAUGAG	1815	CUCAUUAUAUUU	3210	AD-26655, AD-26656
  1243	AAUAUAAUGAGG	1816	CCUCAUUAUAUU	3211	AD-26655, AD-26657
  1244	AUAUAAUGAGGA	1817	UCCUCAUUAUAU	3212	AD-26655, AD-26656,
  					AD-26657
  1245	UAUAAUGAGGAC	1818	GUCCUCAUUAUA	3213	AD-26655, AD-26656,
  					AD-26657
  1246	AUAAUGAGGACC	1819	GGUCCUCAUUAU	3214	AD-26655, AD-26656,
  					AD-26657
  1247	UAAUGAGGACCU	1820	AGGUCCUCAUUA	3215	AD-26658, AD-26655,
  					AD-26656, AD-26657
  1248	AAUGAGGACCUA	1821	UAGGUCCUCAUU	3216	AD-26658, AD-26655,
  					AD-26657
  1249	AUGAGGACCUAU	1822	AUAGGUCCUCAU	3217	AD-26658, AD-26656,
  					AD-26657
  1250	UGAGGACCUAUA	1823	UAUAGGUCCUCA	3218	AD-26658, AD-26657
  1285	ACAAGCAGAGUG	1824	CACUCUGCUUGU	3219	AD-18945, AD-26660
  1286	CAAGCAGAGUGC	1825	GCACUCUGCUUG	3220	AD-18945, AD-26660
  1287	AAGCAGAGUGCU	1826	AGCACUCUGCUU	3221	AD-18945, AD-26660
  1288	AGCAGAGUGCUG	1827	CAGCACUCUGCU	3222	AD-18945, AD-19046
  1289	GCAGAGUGCUGA	1828	UCAGCACUCUGC	3223	AD-18945, AD-26660,
  					AD-19046
  1290	CAGAGUGCUGAA	1829	UUCAGCACUCUG	3224	AD-18945, AD-26660,
  					AD-19046, AD-26661
  1291	AGAGUGCUGAAG	1830	CUUCAGCACUCU	3225	AD-18945, AD-19046,
  					AD-26661, AD-26662
  1292	GAGUGCUGAAGG	1831	CCUUCAGCACUC	3226	AD-18945, AD-19046,
  					AD-26662
  1293	AGUGCUGAAGGU	1832	ACCUUCAGCACU	3227	AD-19046, AD-26661,
  					AD-26662
  1294	GUGCUGAAGGUG	1833	CACCUUCAGCAC	3228	AD-19046, AD-26662
  1295	UGCUGAAGGUGC	1834	GCACCUUCAGCA	3229	AD-26661, AD-26662
  1296	GCUGAAGGUGCU	1835	AGCACCUUCAGC	3230	AD-26661, AD-26662
  1297	CUGAAGGUGCUA	1836	UAGCACCUUCAG	3231	AD-26661, AD-26662
  1313	UCUGCUCUAGUA	1837	UACUAGAGCAGA	3232	AD-19768, AD-19748
  1314	CUGCUCUAGUAA	1838	UUACUAGAGCAG	3233	AD-19768, AD-19748
  1315	UGCUCUAGUAAU	1839	AUUACUAGAGCA	3234	AD-19768, AD-19748
  1316	GCUCUAGUAAUA	1840	UAUUACUAGAGC	3235	AD-19768, AD-19748
  1317	CUCUAGUAAUAA	1841	UUAUUACUAGAG	3236	AD-19768, AD-19748
  1318	UCUAGUAAUAAG	1842	CUUAUUACUAGA	3237	AD-19768, AD-19748
  1319	CUAGUAAUAAGC	1843	GCUUAUUACUAG	3238	AD-19768, AD-19748
  1337	UUGUAGAAGCUG	1844	CAGCUUCUACAA	3239	AD-26664, AD-26663
  1338	UGUAGAAGCUGG	1845	CCAGCUUCUACA	3240	AD-26664, AD-26663
  1339	GUAGAAGCUGGU	1846	ACCAGCUUCUAC	3241	AD-26664, AD-26663
  1340	UAGAAGCUGGUG	1847	CACCAGCUUCUA	3242	AD-26664, AD-26663
  1341	AGAAGCUGGUGG	1848	CCACCAGCUUCU	3243	AD-26664, AD-26663
  1342	GAAGCUGGUGGA	1849	UCCACCAGCUUC	3244	AD-26664, AD-26663
  1343	AAGCUGGUGGAA	1850	UUCCACCAGCUU	3245	AD-26664, AD-26663
  1346	CUGGUGGAAUGC	1851	GCAUUCCACCAG	3246	AD-26665, AD-26666
  1347	UGGUGGAAUGCA	1852	UGCAUUCCACCA	3247	AD-26665, AD-26666
  1348	GGUGGAAUGCAA	1853	UUGCAUUCCACC	3248	AD-26665, AD-26666
  1349	GUGGAAUGCAAG	1854	CUUGCAUUCCAC	3249	AD-26665, AD-26666
  1350	UGGAAUGCAAGC	1855	GCUUGCAUUCCA	3250	AD-26665, AD-26666
  1351	GGAAUGCAAGCU	1856	AGCUUGCAUUCC	3251	AD-26665, AD-26666
  1352	GAAUGCAAGCUU	1857	AAGCUUGCAUUC	3252	AD-26665, AD-26666
  1369	CUUCACCUGACA	1858	UGUCAGGUGAAG	3253	AD-26667, AD-26668
  1370	UUCACCUGACAG	1859	CUGUCAGGUGAA	3254	AD-26667, AD-26668
  1371	UCACCUGACAGA	1860	UCUGUCAGGUGA	3255	AD-26667, AD-26668
  1372	CACCUGACAGAU	1861	AUCUGUCAGGUG	3256	AD-26667, AD-26668
  1374	CCUGACAGAUCC	1862	GGAUCUGUCAGG	3257	AD-26669, AD-26668
  1375	CUGACAGAUCCA	1863	UGGAUCUGUCAG	3258	AD-26669, AD-26668
  1376	UGACAGAUCCAA	1864	UUGGAUCUGUCA	3259	AD-26669, AD-26668
  1380	AGAUCCAAGUCA	1865	UGACUUGGAUCU	3260	AD-26669, AD-26670
  1381	GAUCCAAGUCAA	1866	UUGACUUGGAUC	3261	AD-26669, AD-26670
  1383	UCCAAGUCAACG	1867	CGUUGACUUGGA	3262	AD-26671, AD-26670
  1384	CCAAGUCAACGU	1868	ACGUUGACUUGG	3263	AD-26671, AD-26670
  1385	CAAGUCAACGUC	1869	GACGUUGACUUG	3264	AD-26671, AD-26670
  1386	AAGUCAACGUCU	1870	AGACGUUGACUU	3265	AD-26671, AD-26670
  1387	AGUCAACGUCUU	1871	AAGACGUUGACU	3266	AD-26671, AD-26670
  1396	CUUGUUCAGAAC	1872	GUUCUGAACAAG	3267	AD-26672, AD-26673
  1397	UUGUUCAGAACU	1873	AGUUCUGAACAA	3268	AD-26672, AD-26673
  1398	UGUUCAGAACUG	1874	CAGUUCUGAACA	3269	AD-26672, AD-26673
  1399	GUUCAGAACUGU	1875	ACAGUUCUGAAC	3270	AD-26672, AD-26673
  1400	UUCAGAACUGUC	1876	GACAGUUCUGAA	3271	AD-26672, AD-26673
  1401	UCAGAACUGUCU	1877	AGACAGUUCUGA	3272	AD-26672, AD-26673
  1402	CAGAACUGUCUU	1878	AAGACAGUUCUG	3273	AD-26672, AD-26673
  1406	ACUGUCUUUGGA	1879	UCCAAAGACAGU	3274	AD-19056, AD-19079
  1407	CUGUCUUUGGAC	1880	GUCCAAAGACAG	3275	AD-19056, AD-19079
  1408	UGUCUUUGGACU	1881	AGUCCAAAGACA	3276	AD-19056, AD-19079
  1409	GUCUUUGGACUC	1882	GAGUCCAAAGAC	3277	AD-26674, AD-19056,
  					AD-19079
  1410	UCUUUGGACUCU	1883	AGAGUCCAAAGA	3278	AD-26674, AD-26675,
  					AD-19056, AD-19079
  1411	CUUUGGACUCUC	1884	GAGAGUCCAAAG	3279	AD-26674, AD-19056,
  					AD-19079
  1412	UUUGGACUCUCA	1885	UGAGAGUCCAAA	3280	AD-26674, AD-26675,
  					AD-19079
  1413	UUGGACUCUCAG	1886	CUGAGAGUCCAA	3281	AD-26675, AD-26676,
  					AD-19079
  1414	UGGACUCUCAGG	1887	CCUGAGAGUCCA	3282	AD-26674, AD-26675,
  					AD-26676, AD-26678
  1415	GGACUCUCAGGA	1888	UCCUGAGAGUCC	3283	AD-26674, AD-26676,
  					AD-26678
  1416	GACUCUCAGGAA	1889	UUCCUGAGAGUC	3284	AD-26674, AD-26675,
  					AD-26676, AD-26678
  1417	ACUCUCAGGAAU	1890	AUUCCUGAGAGU	3285	AD-26675, AD-26676,
  					AD-26678
  1418	CUCUCAGGAAUC	1891	GAUUCCUGAGAG	3286	AD-26676, AD-26678
  1419	UCUCAGGAAUCU	1892	AGAUUCCUGAGA	3287	AD-26679, AD-26676,
  					AD-26678
  1420	CUCAGGAAUCUU	1893	AAGAUUCCUGAG	3288	AD-26679, AD-26678
  1421	UCAGGAAUCUUU	1894	AAAGAUUCCUGA	3289	AD-26679, AD-26678
  1426	AAUCUUUCAGAU	1895	AUCUGAAAGAUU	3290	AD-26679, AD-26680
  1429	CUUUCAGAUGCU	1896	AGCAUCUGAAAG	3291	AD-26681, AD-26680
  1430	UUUCAGAUGCUG	1897	CAGCAUCUGAAA	3292	AD-26681, AD-26680
  1431	UUCAGAUGCUGC	1898	GCAGCAUCUGAA	3293	AD-26682, AD-26680
  1432	UCAGAUGCUGCA	1899	UGCAGCAUCUGA	3294	AD-26682, AD-26681
  1433	CAGAUGCUGCAA	1900	UUGCAGCAUCUG	3295	AD-26682, AD-26681,
  					AD-26680
  1434	AGAUGCUGCAAC	1901	GUUGCAGCAUCU	3296	AD-26682, AD-26681
  1435	GAUGCUGCAACU	1902	AGUUGCAGCAUC	3297	AD-26682, AD-26681
  1436	AUGCUGCAACUA	1903	UAGUUGCAGCAU	3298	AD-26682, AD-26681
  1437	UGCUGCAACUAA	1904	UUAGUUGCAGCA	3299	AD-26682, AD-26683
  1438	GCUGCAACUAAA	1905	UUUAGUUGCAGC	3300	AD-26682, AD-26683
  1467	UCUCCUUGGGAC	1906	GUCCCAAGGAGA	3301	AD-26687, AD-26686
  1468	CUCCUUGGGACU	1907	AGUCCCAAGGAG	3302	AD-26687, AD-26686
  1469	UCCUUGGGACUC	1908	GAGUCCCAAGGA	3303	AD-26687, AD-26686
  1470	CCUUGGGACUCU	1909	AGAGUCCCAAGG	3304	AD-26687, AD-26686
  1471	CUUGGGACUCUU	1910	AAGAGUCCCAAG	3305	AD-26687, AD-26686
  1473	UGGGACUCUUGU	1911	ACAAGAGUCCCA	3306	AD-26688, AD-26687
  1474	GGGACUCUUGUU	1912	AACAAGAGUCCC	3307	AD-26688, AD-26687
  1480	CUUGUUCAGCUU	1913	AAGCUGAACAAG	3308	AD-26689, AD-26688
  1485	UCAGCUUCUGGG	1914	CCCAGAAGCUGA	3309	AD-26689, AD-26690
  1486	CAGCUUCUGGGU	1915	ACCCAGAAGCUG	3310	AD-26689, AD-26690
  1487	AGCUUCUGGGUU	1916	AACCCAGAAGCU	3311	AD-26689, AD-26690
  1488	GCUUCUGGGUUC	1917	GAACCCAGAAGC	3312	AD-26691, AD-26690
  1489	CUUCUGGGUUCA	1918	UGAACCCAGAAG	3313	AD-26692, AD-26691,
  					AD-26690
  1490	UUCUGGGUUCAG	1919	CUGAACCCAGAA	3314	AD-26692, AD-26691,
  					AD-26694, AD-26690
  1491	UCUGGGUUCAGA	1920	UCUGAACCCAGA	3315	AD-26692, AD-26694,
  					AD-26690
  1492	CUGGGUUCAGAU	1921	AUCUGAACCCAG	3316	AD-26692, AD-26691,
  					AD-26694, AD-26695,
  					AD-26690
  1493	UGGGUUCAGAUG	1922	CAUCUGAACCCA	3317	AD-26692, AD-26691,
  					AD-26696, AD-26694,
  					AD-26695
  1494	GGGUUCAGAUGA	1923	UCAUCUGAACCC	3318	AD-26692, AD-26691,
  					AD-26696, AD-26694
  1495	GGUUCAGAUGAU	1924	AUCAUCUGAACC	3319	AD-26692, AD-26691,
  					AD-26694, AD-26695
  1496	GUUCAGAUGAUA	1925	UAUCAUCUGAAC	3320	AD-26696, AD-26694,
  					AD-26695
  1497	UUCAGAUGAUAU	1926	AUAUCAUCUGAA	3321	AD-26696, AD-26694,
  					AD-26695
  1498	UCAGAUGAUAUA	1927	UAUAUCAUCUGA	3322	AD-26696, AD-26695
  1499	CAGAUGAUAUAA	1928	UUAUAUCAUCUG	3323	AD-26696, AD-26695
  1503	UGAUAUAAAUGU	1929	ACAUUUAUAUCA	3324	AD-18994, AD-18927
  1504	GAUAUAAAUGUG	1930	CACAUUUAUAUC	3325	AD-19045, AD-18994
  1505	AUAUAAAUGUGG	1931	CCACAUUUAUAU	3326	AD-19045, AD-18927
  1506	UAUAAAUGUGGU	1932	ACCACAUUUAUA	3327	AD-18994, AD-18927
  1507	AUAAAUGUGGUC	1933	GACCACAUUUAU	3328	AD-19045, AD-18994,
  					AD-18927
  1508	UAAAUGUGGUCA	1934	UGACCACAUUUA	3329	AD-19045, AD-18994,
  					AD-18927
  1509	AAAUGUGGUCAC	1935	GUGACCACAUUU	3330	AD-19045, AD-18994
  1510	AAUGUGGUCACC	1936	GGUGACCACAUU	3331	AD-19045, AD-18994
  1517	UCACCUGUGCAG	1937	CUGCACAGGUGA	3332	AD-26697, AD-26698
  1518	CACCUGUGCAGC	1938	GCUGCACAGGUG	3333	AD-26697, AD-26698
  1519	ACCUGUGCAGCU	1939	AGCUGCACAGGU	3334	AD-26697, AD-26699
  1520	CCUGUGCAGCUG	1940	CAGCUGCACAGG	3335	AD-26697, AD-26699,
  					AD-26698
  1521	CUGUGCAGCUGG	1941	CCAGCUGCACAG	3336	AD-26700, AD-26697,
  					AD-26699, AD-26698
  1522	UGUGCAGCUGGA	1942	UCCAGCUGCACA	3337	AD-26700, AD-26697,
  					AD-26699, AD-26701,
  					AD-26698
  1523	GUGCAGCUGGAA	1943	UUCCAGCUGCAC	3338	AD-26700, AD-26699,
  					AD-26701, AD-26698
  1524	UGCAGCUGGAAU	1944	AUUCCAGCUGCA	3339	AD-26700, AD-26699,
  					AD-26701, AD-26698
  1525	GCAGCUGGAAUU	1945	AAUUCCAGCUGC	3340	AD-26700, AD-26699,
  					AD-26701, AD-26702
  1526	CAGCUGGAAUUC	1946	GAAUUCCAGCUG	3341	AD-26700, AD-26701,
  					AD-26702
  1527	AGCUGGAAUUCU	1947	AGAAUUCCAGCU	3342	AD-26700, AD-26703,
  					AD-26702
  1528	GCUGGAAUUCUU	1948	AAGAAUUCCAGC	3343	AD-26700, AD-26703,
  					AD-26701, AD-26702
  1529	CUGGAAUUCUUU	1949	AAAGAAUUCCAG	3344	AD-26703, AD-26701,
  					AD-26702
  1530	UGGAAUUCUUUC	1950	GAAAGAAUUCCA	3345	AD-26703, AD-26702
  1531	GGAAUUCUUUCU	1951	AGAAAGAAUUCC	3346	AD-26703, AD-26702
  1532	GAAUUCUUUCUA	1952	UAGAAAGAAUUC	3347	AD-26703, AD-26702
  1538	UUUCUAACCUCA	1953	UGAGGUUAGAAA	3348	AD-26704, AD-26920
  1539	UUCUAACCUCAC	1954	GUGAGGUUAGAA	3349	AD-26704, AD-26920,
  					AD-26705
  1540	UCUAACCUCACU	1955	AGUGAGGUUAGA	3350	AD-26704, AD-26920,
  					AD-26705, AD-18899
  1541	CUAACCUCACUU	1956	AAGUGAGGUUAG	3351	AD-26704, AD-26920,
  					AD-26705, AD-18899,
  					AD-18917
  1542	UAACCUCACUUG	1957	CAAGUGAGGUUA	3352	AD-26704, AD-26705,
  					AD-18899, AD-18917
  1543	AACCUCACUUGC	1958	GCAAGUGAGGUU	3353	AD-26704, AD-19074,
  					AD-26705, AD-18899,
  					AD-18917
  1544	ACCUCACUUGCA	1959	UGCAAGUGAGGU	3354	AD-26704, AD-26706,
  					AD-19074, AD-26705,
  					AD-18899, AD-18917
  1545	CCUCACUUGCAA	1960	UUGCAAGUGAGG	3355	AD-26704, AD-26706,
  					AD-26707, AD-19074,
  					AD-26705, AD-18899,
  					AD-18917
  1546	CUCACUUGCAAU	1961	AUUGCAAGUGAG	3356	AD-26706, AD-26707,
  					AD-19074, AD-26708,
  					AD-26705, AD-18899,
  					AD-18917
  1547	UCACUUGCAAUA	1962	UAUUGCAAGUGA	3357	AD-26706, AD-26134,
  					AD-26707, AD-19074,
  					AD-26708, AD-18899,
  					AD-18917
  1548	CACUUGCAAUAA	1963	UUAUUGCAAGUG	3358	AD-26706, AD-26134,
  					AD-26707, AD-19074,
  					AD-26708, AD-18917
  1549	ACUUGCAAUAAU	1964	AUUAUUGCAAGU	3359	AD-26706, AD-26134,
  					AD-26707, AD-19074,
  					AD-26708
  1550	CUUGCAAUAAUU	1965	AAUUAUUGCAAG	3360	AD-26706, AD-26134,
  					AD-26707, AD-19074,
  					AD-26708, AD-26135
  1551	UUGCAAUAAUUA	1966	UAAUUAUUGCAA	3361	AD-26706, AD-26134,
  					AD-26707, AD-26708,
  					AD-26135
  1552	UGCAAUAAUUAU	1967	AUAAUUAUUGCA	3362	AD-26134, AD-26707,
  					AD-26708, AD-26135
  1553	GCAAUAAUUAUA	1968	UAUAAUUAUUGC	3363	AD-26134, AD-26708,
  					AD-26135
  1554	CAAUAAUUAUAA	1969	UUAUAAUUAUUG	3364	AD-26134, AD-26135
  1580	UCUGCCAAGUGG	1970	CCACUUGGCAGA	3365	AD-26710, AD-26709
  1581	CUGCCAAGUGGG	1971	CCCACUUGGCAG	3366	AD-26710, AD-26709
  1582	UGCCAAGUGGGU	1972	ACCCACUUGGCA	3367	AD-26710, AD-26709
  1583	GCCAAGUGGGUG	1973	CACCCACUUGGC	3368	AD-26710, AD-26709
  1584	CCAAGUGGGUGG	1974	CCACCCACUUGG	3369	AD-26710, AD-26709
  1585	CAAGUGGGUGGU	1975	ACCACCCACUUG	3370	AD-26710, AD-26709
  1586	AAGUGGGUGGUA	1976	UACCACCCACUU	3371	AD-26710, AD-26709
  1597	AUAGAGGCUCUU	1977	AAGAGCCUCUAU	3372	AD-26712, AD-26711
  1628	CUGGUGACAGGG	1978	CCCUGUCACCAG	3373	AD-26714, AD-26141
  1629	UGGUGACAGGGA	1979	UCCCUGUCACCA	3374	AD-26714, AD-26141
  1630	GGUGACAGGGAA	1980	UUCCCUGUCACC	3375	AD-26714, AD-26141
  1637	GGGAAGACAUCA	1981	UGAUGUCUUCCC	3376	AD-18938, AD-19064
  1638	GGAAGACAUCAC	1982	GUGAUGUCUUCC	3377	AD-18938, AD-18937
  1639	GAAGACAUCACU	1983	AGUGAUGUCUUC	3378	AD-18938, AD-19064
  1640	AAGACAUCACUG	1984	CAGUGAUGUCUU	3379	AD-19064, AD-18937
  1641	AGACAUCACUGA	1985	UCAGUGAUGUCU	3380	AD-18938, AD-19064,
  					AD-18937
  1642	GACAUCACUGAG	1986	CUCAGUGAUGUC	3381	AD-18938, AD-19064,
  					AD-18937
  1643	ACAUCACUGAGC	1987	GCUCAGUGAUGU	3382	AD-18938, AD-19064,
  					AD-18937, AD-26715
  1644	CAUCACUGAGCC	1988	GGCUCAGUGAUG	3383	AD-18938, AD-18937,
  					AD-26715
  1645	AUCACUGAGCCU	1989	AGGCUCAGUGAU	3384	AD-18937, AD-26715
  1654	CCUGCCAUCUGU	1990	ACAGAUGGCAGG	3385	AD-26716, AD-18990
  1655	CUGCCAUCUGUG	1991	CACAGAUGGCAG	3386	AD-26716, AD-18990
  1656	UGCCAUCUGUGC	1992	GCACAGAUGGCA	3387	AD-26716, AD-18990
  1657	GCCAUCUGUGCU	1993	AGCACAGAUGGC	3388	AD-26716, AD-18990,
  					AD-19061
  1658	CCAUCUGUGCUC	1994	GAGCACAGAUGG	3389	AD-26716, AD-18990,
  					AD-18893, AD-19061
  1659	CAUCUGUGCUCU	1995	AGAGCACAGAUG	3390	AD-26716, AD-18946,
  					AD-18990, AD-18893,
  					AD-19061
  1660	AUCUGUGCUCUU	1996	AAGAGCACAGAU	3391	AD-26716, AD-18946,
  					AD-18990, AD-19082,
  					AD-18893, AD-19061
  1661	UCUGUGCUCUUC	1997	GAAGAGCACAGA	3392	AD-18946, AD-18990,
  					AD-19082, AD-18893,
  					AD-19061
  1662	CUGUGCUCUUCG	1998	CGAAGAGCACAG	3393	AD-18946, AD-19082,
  					AD-19061
  1663	UGUGCUCUUCGU	1999	ACGAAGAGCACA	3394	AD-18946, AD-19082,
  					AD-18893, AD-19061
  1664	GUGCUCUUCGUC	2000	GACGAAGAGCAC	3395	AD-18946, AD-18904,
  					AD-19082, AD-18893,
  					AD-19061
  1665	UGCUCUUCGUCA	2001	UGACGAAGAGCA	3396	AD-18946, AD-18904,
  					AD-19082, AD-18893
  1666	GCUCUUCGUCAU	2002	AUGACGAAGAGC	3397	AD-18946, AD-18932,
  					AD-18904, AD-19082
  1667	CUCUUCGUCAUC	2003	GAUGACGAAGAG	3398	AD-18932, AD-19082,
  					AD-18943
  1668	UCUUCGUCAUCU	2004	AGAUGACGAAGA	3399	AD-18932, AD-18904,
  					AD-18943
  1669	CUUCGUCAUCUG	2005	CAGAUGACGAAG	3400	AD-18904, AD-19002,
  					AD-18943
  1670	UUCGUCAUCUGA	2006	UCAGAUGACGAA	3401	AD-18932, AD-18904,
  					AD-19002, AD-18943
  1671	UCGUCAUCUGAC	2007	GUCAGAUGACGA	3402	AD-18904, AD-18943
  1672	CGUCAUCUGACC	2008	GGUCAGAUGACG	3403	AD-18932, AD-19002,
  					AD-18943
  1673	GUCAUCUGACCA	2009	UGGUCAGAUGAC	3404	AD-18932, AD-18943
  1674	UCAUCUGACCAG	2010	CUGGUCAGAUGA	3405	AD-19002, AD-18943
  1677	UCUGACCAGCCG	2011	CGGCUGGUCAGA	3406	AD-26717, AD-19761
  1678	CUGACCAGCCGA	2012	UCGGCUGGUCAG	3407	AD-26717, AD-19761
  1679	UGACCAGCCGAC	2013	GUCGGCUGGUCA	3408	AD-26717, AD-19761
  1680	GACCAGCCGACA	2014	UGUCGGCUGGUC	3409	AD-26717, AD-19761
  1681	ACCAGCCGACAC	2015	GUGUCGGCUGGU	3410	AD-26717, AD-26718
  1682	CCAGCCGACACC	2016	GGUGUCGGCUGG	3411	AD-26717, AD-26718,
  					AD-19761
  1683	CAGCCGACACCA	2017	UGGUGUCGGCUG	3412	AD-26717, AD-26718,
  					AD-19761
  1684	AGCCGACACCAA	2018	UUGGUGUCGGCU	3413	AD-26717, AD-26718
  1704	GAUGGCCCAGAA	2019	UUCUGGGCCAUC	3414	AD-26721, AD-26720
  1705	AUGGCCCAGAAU	2020	AUUCUGGGCCAU	3415	AD-26721, AD-26720
  1710	CCAGAAUGCAGU	2021	ACUGCAUUCUGG	3416	AD-26721, AD-26722
  1711	CAGAAUGCAGUU	2022	AACUGCAUUCUG	3417	AD-26721, AD-26722
  1713	GAAUGCAGUUCG	2023	CGAACUGCAUUC	3418	AD-26722, AD-19741
  1714	AAUGCAGUUCGC	2024	GCGAACUGCAUU	3419	AD-26722, AD-19741
  1715	AUGCAGUUCGCC	2025	GGCGAACUGCAU	3420	AD-26722, AD-19741,
  					AD-26723
  1716	UGCAGUUCGCCU	2026	AGGCGAACUGCA	3421	AD-26724, AD-26722,
  					AD-19741, AD-26723
  1717	GCAGUUCGCCUU	2027	AAGGCGAACUGC	3422	AD-26724, AD-19741,
  					AD-26723
  1718	CAGUUCGCCUUC	2028	GAAGGCGAACUG	3423	AD-26724, AD-26723
  1719	AGUUCGCCUUCA	2029	UGAAGGCGAACU	3424	AD-26724, AD-19741
  1720	GUUCGCCUUCAC	2030	GUGAAGGCGAAC	3425	AD-19741, AD-26723
  1721	UUCGCCUUCACU	2031	AGUGAAGGCGAA	3426	AD-26724, AD-26723
  1722	UCGCCUUCACUA	2032	UAGUGAAGGCGA	3427	AD-26724, AD-26725,
  					AD-26723
  1723	CGCCUUCACUAU	2033	AUAGUGAAGGCG	3428	AD-26724, AD-26725
  1728	UCACUAUGGACU	2034	AGUCCAUAGUGA	3429	AD-26725, AD-26726
  1729	CACUAUGGACUA	2035	UAGUCCAUAGUG	3430	AD-26725, AD-26726
  1734	UGGACUACCAGU	2036	ACUGGUAGUCCA	3431	AD-26727, AD-26726
  1735	GGACUACCAGUU	2037	AACUGGUAGUCC	3432	AD-26727, AD-26728
  1736	GACUACCAGUUG	2038	CAACUGGUAGUC	3433	AD-26728, AD-26729
  1737	ACUACCAGUUGU	2039	ACAACUGGUAGU	3434	AD-26727, AD-26729
  1738	CUACCAGUUGUG	2040	CACAACUGGUAG	3435	AD-26727, AD-26728,
  					AD-26729
  1739	UACCAGUUGUGG	2041	CCACAACUGGUA	3436	AD-26727, AD-26728,
  					AD-26729
  1740	ACCAGUUGUGGU	2042	ACCACAACUGGU	3437	AD-26727, AD-26728,
  					AD-26729
  1741	CCAGUUGUGGUU	2043	AACCACAACUGG	3438	AD-26727, AD-26728,
  					AD-26729
  1742	CAGUUGUGGUUA	2044	UAACCACAACUG	3439	AD-26728, AD-26730,
  					AD-26729
  1743	AGUUGUGGUUAA	2045	UUAACCACAACU	3440	AD-26731, AD-26730,
  					AD-26729
  1744	GUUGUGGUUAAG	2046	CUUAACCACAAC	3441	AD-26731, AD-26730
  1745	UUGUGGUUAAGC	2047	GCUUAACCACAA	3442	AD-26731, AD-26730
  1746	UGUGGUUAAGCU	2048	AGCUUAACCACA	3443	AD-26731, AD-26730
  1747	GUGGUUAAGCUC	2049	GAGCUUAACCAC	3444	AD-26731, AD-26730
  1748	UGGUUAAGCUCU	2050	AGAGCUUAACCA	3445	AD-26731, AD-26730
  1749	GGUUAAGCUCUU	2051	AAGAGCUUAACC	3446	AD-26731, AD-26730
  1770	AUCCCACUGGCC	2052	GGCCAGUGGGAU	3447	AD-26734, AD-26733
  1771	UCCCACUGGCCU	2053	AGGCCAGUGGGA	3448	AD-26734, AD-26733,
  					AD-26735
  1772	CCCACUGGCCUC	2054	GAGGCCAGUGGG	3449	AD-26734, AD-18963,
  					AD-26733, AD-26735
  1773	CCACUGGCCUCU	2055	AGAGGCCAGUGG	3450	AD-26734, AD-18930,
  					AD-18963, AD-26733,
  					AD-26735
  1774	CACUGGCCUCUG	2056	CAGAGGCCAGUG	3451	AD-26734, AD-18930,
  					AD-18963, AD-26733,
  					AD-26735, AD-19078
  1775	ACUGGCCUCUGA	2057	UCAGAGGCCAGU	3452	AD-26734, AD-18930,
  					AD-18963, AD-26733,
  					AD-18948, AD-19078
  1776	CUGGCCUCUGAU	2058	AUCAGAGGCCAG	3453	AD-26734, AD-18963,
  					AD-26733, AD-26735,
  					AD-18948, AD-19078
  1777	UGGCCUCUGAUA	2059	UAUCAGAGGCCA	3454	AD-26734, AD-18930,
  					AD-26736, AD-18963,
  					AD-26735, AD-18948,
  					AD-19078
  1778	GGCCUCUGAUAA	2060	UUAUCAGAGGCC	3455	AD-18930, AD-26736,
  					AD-18963, AD-26735,
  					AD-18948, AD-19078
  1779	GCCUCUGAUAAA	2061	UUUAUCAGAGGC	3456	AD-18930, AD-26736,
  					AD-18963, AD-18948,
  					AD-19078
  1780	CCUCUGAUAAAG	2062	CUUUAUCAGAGG	3457	AD-18930, AD-26736,
  					AD-18948, AD-19078
  1781	CUCUGAUAAAGG	2063	CCUUUAUCAGAG	3458	AD-26736, AD-18948,
  					AD-19078
  1782	UCUGAUAAAGGC	2064	GCCUUUAUCAGA	3459	AD-26736, AD-18948,
  					AD-26737
  1783	CUGAUAAAGGCU	2065	AGCCUUUAUCAG	3460	AD-26736, AD-26737
  1784	UGAUAAAGGCUA	2066	UAGCCUUUAUCA	3461	AD-26736, AD-26737
  1786	AUAAAGGCUACU	2067	AGUAGCCUUUAU	3462	AD-26738, AD-26737
  1787	UAAAGGCUACUG	2068	CAGUAGCCUUUA	3463	AD-26738, AD-26737
  1788	AAAGGCUACUGU	2069	ACAGUAGCCUUU	3464	AD-26738, AD-26737
  1789	AAGGCUACUGUU	2070	AACAGUAGCCUU	3465	AD-26738, AD-26737
  1791	GGCUACUGUUGG	2071	CCAACAGUAGCC	3466	AD-26738, AD-26739
  1792	GCUACUGUUGGA	2072	UCCAACAGUAGC	3467	AD-26738, AD-26739
  1793	CUACUGUUGGAU	2073	AUCCAACAGUAG	3468	AD-26738, AD-26739
  1795	ACUGUUGGAUUG	2074	CAAUCCAACAGU	3469	AD-18983, AD-26739
  1796	CUGUUGGAUUGA	2075	UCAAUCCAACAG	3470	AD-18983, AD-26739,
  					AD-18897
  1797	UGUUGGAUUGAU	2076	AUCAAUCCAACA	3471	AD-26740, AD-18983,
  					AD-26739, AD-18897
  1798	GUUGGAUUGAUU	2077	AAUCAAUCCAAC	3472	AD-26740, AD-26739,
  					AD-18897
  1799	UUGGAUUGAUUC	2078	GAAUCAAUCCAA	3473	AD-26740, AD-18983,
  					AD-18897
  1800	UGGAUUGAUUCG	2079	CGAAUCAAUCCA	3474	AD-26740, AD-18897,
  					AD-26921
  1801	GGAUUGAUUCGA	2080	UCGAAUCAAUCC	3475	AD-26740, AD-18983,
  					AD-18897, AD-26921
  1802	GAUUGAUUCGAA	2081	UUCGAAUCAAUC	3476	AD-18983, AD-18897,
  					AD-26921
  1803	AUUGAUUCGAAA	2082	UUUCGAAUCAAU	3477	AD-26740, AD-18897,
  					AD-26921
  1804	UUGAUUCGAAAU	2083	AUUUCGAAUCAA	3478	AD-26740, AD-26921
  1848	GCGUGAGCAGGG	2084	CCCUGCUCACGC	3479	AD-26175, AD-26176
  1849	CGUGAGCAGGGU	2085	ACCCUGCUCACG	3480	AD-26175, AD-26176
  1850	GUGAGCAGGGUG	2086	CACCCUGCUCAC	3481	AD-26175, AD-26176
  1851	UGAGCAGGGUGC	2087	GCACCCUGCUCA	3482	AD-26175, AD-26176
  1852	GAGCAGGGUGCC	2088	GGCACCCUGCUC	3483	AD-26175, AD-26176
  1853	AGCAGGGUGCCA	2089	UGGCACCCUGCU	3484	AD-26175, AD-26176
  1854	GCAGGGUGCCAU	2090	AUGGCACCCUGC	3485	AD-26175, AD-26176
  1859	GUGCCAUUCCAC	2091	GUGGAAUGGCAC	3486	AD-19742, AD-19749
  1860	UGCCAUUCCACG	2092	CGUGGAAUGGCA	3487	AD-26741, AD-19749
  1861	GCCAUUCCACGA	2093	UCGUGGAAUGGC	3488	AD-26741, AD-19742
  1862	CCAUUCCACGAC	2094	GUCGUGGAAUGG	3489	AD-26741, AD-19742,
  					AD-19749
  1863	CAUUCCACGACU	2095	AGUCGUGGAAUG	3490	AD-26741, AD-19742,
  					AD-19749, AD-19762
  1864	AUUCCACGACUA	2096	UAGUCGUGGAAU	3491	AD-26741, AD-19742,
  					AD-19749
  1865	UUCCACGACUAG	2097	CUAGUCGUGGAA	3492	AD-26742, AD-26741,
  					AD-19742, AD-19749,
  					AD-19762
  1866	UCCACGACUAGU	2098	ACUAGUCGUGGA	3493	AD-26742, AD-26741,
  					AD-19749, AD-19762
  1867	CCACGACUAGUU	2099	AACUAGUCGUGG	3494	AD-26742, AD-26741,
  					AD-19751, AD-19762
  1868	CACGACUAGUUC	2100	GAACUAGUCGUG	3495	AD-26742, AD-19751,
  					AD-19762, AD-19752
  1869	ACGACUAGUUCA	2101	UGAACUAGUCGU	3496	AD-26742, AD-26743,
  					AD-19751, AD-19762
  1870	CGACUAGUUCAG	2102	CUGAACUAGUCG	3497	AD-26742, AD-26743,
  					AD-19751, AD-19762,
  					AD-19752
  1871	GACUAGUUCAGU	2103	ACUGAACUAGUC	3498	AD-26742, AD-26743,
  					AD-19751, AD-19752
  1872	ACUAGUUCAGUU	2104	AACUGAACUAGU	3499	AD-26742, AD-26743,
  					AD-19751, AD-19752,
  					AD-26744
  1873	CUAGUUCAGUUG	2105	CAACUGAACUAG	3500	AD-26743, AD-19752,
  					AD-26744
  1874	UAGUUCAGUUGC	2106	GCAACUGAACUA	3501	AD-26743, AD-19751,
  					AD-19752, AD-26744
  1875	AGUUCAGUUGCU	2107	AGCAACUGAACU	3502	AD-26743, AD-19753,
  					AD-26744
  1876	GUUCAGUUGCUU	2108	AAGCAACUGAAC	3503	AD-26743, AD-19753,
  					AD-26744
  1877	UUCAGUUGCUUG	2109	CAAGCAACUGAA	3504	AD-19753, AD-26744
  1878	UCAGUUGCUUGU	2110	ACAAGCAACUGA	3505	AD-19753, AD-26744
  1879	CAGUUGCUUGUU	2111	AACAAGCAACUG	3506	AD-19753, AD-26744
  1881	GUUGCUUGUUCG	2112	CGAACAAGCAAC	3507	AD-19753, AD-26745
  1882	UUGCUUGUUCGU	2113	ACGAACAAGCAA	3508	AD-19753, AD-26745
  1887	UGUUCGUGCACA	2114	UGUGCACGAACA	3509	AD-26746, AD-26745
  1888	GUUCGUGCACAU	2115	AUGUGCACGAAC	3510	AD-26746, AD-26747,
  					AD-26745
  1889	UUCGUGCACAUC	2116	GAUGUGCACGAA	3511	AD-26746, AD-26747
  1890	UCGUGCACAUCA	2117	UGAUGUGCACGA	3512	AD-26746, AD-26747
  1891	CGUGCACAUCAG	2118	CUGAUGUGCACG	3513	AD-26746, AD-26747
  1892	GUGCACAUCAGG	2119	CCUGAUGUGCAC	3514	AD-26746, AD-26747
  1893	UGCACAUCAGGA	2120	UCCUGAUGUGCA	3515	AD-26746, AD-26747
  1894	GCACAUCAGGAU	2121	AUCCUGAUGUGC	3516	AD-26746, AD-26747
  1907	CCCAGCGCCGUA	2122	UACGGCGCUGGG	3517	AD-19738, AD-19754
  1908	CCAGCGCCGUAC	2123	GUACGGCGCUGG	3518	AD-19738, AD-19754
  1909	CAGCGCCGUACG	2124	CGUACGGCGCUG	3519	AD-19738, AD-19754
  1910	AGCGCCGUACGU	2125	ACGUACGGCGCU	3520	AD-19738, AD-19754
  1911	GCGCCGUACGUC	2126	GACGUACGGCGC	3521	AD-19738, AD-19754
  1912	CGCCGUACGUCC	2127	GGACGUACGGCG	3522	AD-19738, AD-19754
  1927	GGUGGGACACAG	2128	CUGUGUCCCACC	3523	AD-26184, AD-26748
  1928	GUGGGACACAGC	2129	GCUGUGUCCCAC	3524	AD-26749, AD-26184,
  					AD-26748
  1929	UGGGACACAGCA	2130	UGCUGUGUCCCA	3525	AD-26749, AD-26750,
  					AD-26184, AD-26748
  1930	GGGACACAGCAG	2131	CUGCUGUGUCCC	3526	AD-26749, AD-26750,
  					AD-26184
  1931	GGACACAGCAGC	2132	GCUGCUGUGUCC	3527	AD-26749, AD-26184,
  					AD-26748
  1932	GACACAGCAGCA	2133	UGCUGCUGUGUC	3528	AD-26749, AD-26750,
  					AD-26184, AD-26748
  1933	ACACAGCAGCAA	2134	UUGCUGCUGUGU	3529	AD-26750, AD-26184,
  					AD-26748
  1934	CACAGCAGCAAU	2135	AUUGCUGCUGUG	3530	AD-26749, AD-26750,
  					AD-26748
  1935	ACAGCAGCAAUU	2136	AAUUGCUGCUGU	3531	AD-26749, AD-26750
  1955	GGGUCCGCAUGG	2137	CCAUGCGGACCC	3532	AD-26751, AD-26752
  1956	GGUCCGCAUGGA	2138	UCCAUGCGGACC	3533	AD-26751, AD-26752
  1957	GUCCGCAUGGAA	2139	UUCCAUGCGGAC	3534	AD-26751, AD-26752
  1958	UCCGCAUGGAAG	2140	CUUCCAUGCGGA	3535	AD-26751, AD-26752
  1959	CCGCAUGGAAGA	2141	UCUUCCAUGCGG	3536	AD-26751, AD-26752
  1960	CGCAUGGAAGAA	2142	UUCUUCCAUGCG	3537	AD-26751, AD-26752
  1961	GCAUGGAAGAAA	2143	UUUCUUCCAUGC	3538	AD-26751, AD-26752
  2001	CAUCCUAGCUCG	2144	CGAGCUAGGAUG	3539	AD-26753, AD-26754
  2002	AUCCUAGCUCGG	2145	CCGAGCUAGGAU	3540	AD-26753, AD-26754
  2003	UCCUAGCUCGGG	2146	CCCGAGCUAGGA	3541	AD-26753, AD-26754
  2004	CCUAGCUCGGGA	2147	UCCCGAGCUAGG	3542	AD-26753, AD-26754
  2005	CUAGCUCGGGAU	2148	AUCCCGAGCUAG	3543	AD-26753, AD-26754
  2006	UAGCUCGGGAUG	2149	CAUCCCGAGCUA	3544	AD-26755, AD-26754
  2007	AGCUCGGGAUGU	2150	ACAUCCCGAGCU	3545	AD-26755, AD-26754
  2008	GCUCGGGAUGUU	2151	AACAUCCCGAGC	3546	AD-26755, AD-26754
  2011	CGGGAUGUUCAC	2152	GUGAACAUCCCG	3547	AD-26755, AD-20124
  2012	GGGAUGUUCACA	2153	UGUGAACAUCCC	3548	AD-26756, AD-26755,
  					AD-20124
  2013	GGAUGUUCACAA	2154	UUGUGAACAUCC	3549	AD-26756, AD-26755,
  					AD-26757, AD-20124
  2014	GAUGUUCACAAC	2155	GUUGUGAACAUC	3550	AD-26756, AD-26757,
  					AD-20124
  2015	AUGUUCACAACC	2156	GGUUGUGAACAU	3551	AD-26756, AD-26757,
  					AD-20124
  2016	UGUUCACAACCG	2157	CGGUUGUGAACA	3552	AD-26756, AD-19750,
  					AD-20124
  2017	GUUCACAACCGA	2158	UCGGUUGUGAAC	3553	AD-19750, AD-26757,
  					AD-20124
  2018	UUCACAACCGAA	2159	UUCGGUUGUGAA	3554	AD-26756, AD-19750,
  					AD-26757, AD-20124
  2019	UCACAACCGAAU	2160	AUUCGGUUGUGA	3555	AD-26756, AD-19750,
  					AD-26757
  2020	CACAACCGAAUU	2161	AAUUCGGUUGUG	3556	AD-19750, AD-26757
  2041	GGACUAAAUACC	2162	GGUAUUUAGUCC	3557	AD-26758, AD-26759
  2042	GACUAAAUACCA	2163	UGGUAUUUAGUC	3558	AD-26758, AD-26759
  2043	ACUAAAUACCAU	2164	AUGGUAUUUAGU	3559	AD-26758, AD-26759
  2044	CUAAAUACCAUU	2165	AAUGGUAUUUAG	3560	AD-26758, AD-26759
  2045	UAAAUACCAUUC	2166	GAAUGGUAUUUA	3561	AD-26760, AD-26759
  2046	AAAUACCAUUCC	2167	GGAAUGGUAUUU	3562	AD-26760, AD-26761,
  					AD-26759
  2047	AAUACCAUUCCA	2168	UGGAAUGGUAUU	3563	AD-26760, AD-26759
  2048	AUACCAUUCCAU	2169	AUGGAAUGGUAU	3564	AD-26760, AD-26761,
  					AD-26759, AD-18982
  2049	UACCAUUCCAUU	2170	AAUGGAAUGGUA	3565	AD-26760, AD-19062,
  					AD-18982
  2050	ACCAUUCCAUUG	2171	CAAUGGAAUGGU	3566	AD-26760, AD-26761,
  					AD-19062, AD-18982
  2051	CCAUUCCAUUGU	2172	ACAAUGGAAUGG	3567	AD-26761, AD-19062,
  					AD-18982
  2052	CAUUCCAUUGUU	2173	AACAAUGGAAUG	3568	AD-26760, AD-26761,
  					AD-19062
  2053	AUUCCAUUGUUU	2174	AAACAAUGGAAU	3569	AD-26761, AD-19062,
  					AD-18982
  2054	UUCCAUUGUUUG	2175	CAAACAAUGGAA	3570	AD-19062, AD-18982
  2055	UCCAUUGUUUGU	2176	ACAAACAAUGGA	3571	AD-19062, AD-18982
  2059	UUGUUUGUGCAG	2177	CUGCACAAACAA	3572	AD-26763, AD-26762
  2060	UGUUUGUGCAGC	2178	GCUGCACAAACA	3573	AD-26764, AD-26763,
  					AD-26762
  2061	GUUUGUGCAGCU	2179	AGCUGCACAAAC	3574	AD-26764, AD-26765,
  					AD-26763, AD-26762
  2062	UUUGUGCAGCUG	2180	CAGCUGCACAAA	3575	AD-26764, AD-26765,
  					AD-26766, AD-26763,
  					AD-26762
  2063	UUGUGCAGCUGC	2181	GCAGCUGCACAA	3576	AD-26764, AD-26765,
  					AD-26766, AD-26763
  2064	UGUGCAGCUGCU	2182	AGCAGCUGCACA	3577	AD-26764, AD-26766,
  					AD-26763, AD-26762
  2065	GUGCAGCUGCUU	2183	AAGCAGCUGCAC	3578	AD-26765, AD-26766,
  					AD-26763, AD-26762
  2066	UGCAGCUGCUUU	2184	AAAGCAGCUGCA	3579	AD-26764, AD-26765,
  					AD-26766, AD-26763
  2067	GCAGCUGCUUUA	2185	UAAAGCAGCUGC	3580	AD-26764, AD-26765,
  					AD-26766
  2068	CAGCUGCUUUAU	2186	AUAAAGCAGCUG	3581	AD-26765, AD-26766
  2069	AGCUGCUUUAUU	2187	AAUAAAGCAGCU	3582	AD-26766, AD-26767
  2070	GCUGCUUUAUUC	2188	GAAUAAAGCAGC	3583	AD-26768, AD-26767
  2071	CUGCUUUAUUCU	2189	AGAAUAAAGCAG	3584	AD-26768, AD-26767
  2072	UGCUUUAUUCUC	2190	GAGAAUAAAGCA	3585	AD-26768, AD-26767
  2073	GCUUUAUUCUCC	2191	GGAGAAUAAAGC	3586	AD-26768, AD-18928
  2074	CUUUAUUCUCCC	2192	GGGAGAAUAAAG	3587	AD-26768, AD-18928,
  					AD-26767
  2075	UUUAUUCUCCCA	2193	UGGGAGAAUAAA	3588	AD-26769, AD-18928,
  					AD-26767
  2076	UUAUUCUCCCAU	2194	AUGGGAGAAUAA	3589	AD-26769, AD-26768,
  					AD-18928, AD-26767
  2077	UAUUCUCCCAUU	2195	AAUGGGAGAAUA	3590	AD-26769, AD-26768,
  					AD-18928
  2078	AUUCUCCCAUUG	2196	CAAUGGGAGAAU	3591	AD-26770, AD-18928
  2079	UUCUCCCAUUGA	2197	UCAAUGGGAGAA	3592	AD-26769, AD-26770
  2080	UCUCCCAUUGAA	2198	UUCAAUGGGAGA	3593	AD-26769, AD-26770
  2081	CUCCCAUUGAAA	2199	UUUCAAUGGGAG	3594	AD-26769, AD-26770
  2082	UCCCAUUGAAAA	2200	UUUUCAAUGGGA	3595	AD-26771, AD-26769,
  					AD-26770
  2083	CCCAUUGAAAAC	2201	GUUUUCAAUGGG	3596	AD-26771, AD-26770
  2084	CCAUUGAAAACA	2202	UGUUUUCAAUGG	3597	AD-26771, AD-26770
  2085	CAUUGAAAACAU	2203	AUGUUUUCAAUG	3598	AD-26771, AD-26770
  2100	AAGAGUAGCUGC	2204	GCAGCUACUCUU	3599	AD-18962, AD-18895
  2101	AGAGUAGCUGCA	2205	UGCAGCUACUCU	3600	AD-18962, AD-18895
  2102	GAGUAGCUGCAG	2206	CUGCAGCUACUC	3601	AD-18962, AD-18895
  2104	GUAGCUGCAGGG	2207	CCCUGCAGCUAC	3602	AD-18962, AD-18976
  2105	UAGCUGCAGGGG	2208	CCCCUGCAGCUA	3603	AD-19003, AD-18962
  2106	AGCUGCAGGGGU	2209	ACCCCUGCAGCU	3604	AD-19003, AD-18962,
  					AD-18976
  2107	GCUGCAGGGGUC	2210	GACCCCUGCAGC	3605	AD-18962, AD-18976
  2108	CUGCAGGGGUCC	2211	GGACCCCUGCAG	3606	AD-19003, AD-18976
  2109	UGCAGGGGUCCU	2212	AGGACCCCUGCA	3607	AD-19003, AD-26772,
  					AD-18976
  2110	GCAGGGGUCCUC	2213	GAGGACCCCUGC	3608	AD-19003, AD-26772,
  					AD-18976
  2111	CAGGGGUCCUCU	2214	AGAGGACCCCUG	3609	AD-18923, AD-19003,
  					AD-26772, AD-18976
  2112	AGGGGUCCUCUG	2215	CAGAGGACCCCU	3610	AD-18923, AD-19003,
  					AD-18955, AD-26772
  2113	GGGGUCCUCUGU	2216	ACAGAGGACCCC	3611	AD-18923, AD-18955,
  					AD-26772
  2114	GGGUCCUCUGUG	2217	CACAGAGGACCC	3612	AD-18923, AD-18934,
  					AD-18955, AD-26772
  2115	GGUCCUCUGUGA	2218	UCACAGAGGACC	3613	AD-18923, AD-18934,
  					AD-19052, AD-18912,
  					AD-18955
  2116	GUCCUCUGUGAA	2219	UUCACAGAGGAC	3614	AD-18923, AD-19052,
  					AD-18912, AD-18955,
  					AD-26772
  2117	UCCUCUGUGAAC	2220	GUUCACAGAGGA	3615	AD-18923, AD-18934,
  					AD-19052, AD-18912,
  					AD-18955
  2118	CCUCUGUGAACU	2221	AGUUCACAGAGG	3616	AD-18923, AD-18934,
  					AD-18973, AD-19052,
  					AD-18912, AD-18955
  2119	CUCUGUGAACUU	2222	AAGUUCACAGAG	3617	AD-18934, AD-18973,
  					AD-19052, AD-18912,
  					AD-18955
  2120	UCUGUGAACUUG	2223	CAAGUUCACAGA	3618	AD-18934, AD-18973,
  					AD-19052, AD-18912
  2121	CUGUGAACUUGC	2224	GCAAGUUCACAG	3619	AD-18973, AD-19052,
  					AD-18912
  2122	UGUGAACUUGCU	2225	AGCAAGUUCACA	3620	AD-18973, AD-19047
  2123	GUGAACUUGCUC	2226	GAGCAAGUUCAC	3621	AD-18973, AD-19047,
  					AD-18971
  2124	UGAACUUGCUCA	2227	UGAGCAAGUUCA	3622	AD-18973, AD-19047,
  					AD-18971, AD-18961
  2125	GAACUUGCUCAG	2228	CUGAGCAAGUUC	3623	AD-18973, AD-19047,
  					AD-18971, AD-18961
  2126	AACUUGCUCAGG	2229	CCUGAGCAAGUU	3624	AD-19047, AD-18984,
  					AD-18971, AD-18961
  2127	ACUUGCUCAGGA	2230	UCCUGAGCAAGU	3625	AD-19047, AD-18984,
  					AD-26773, AD-18971,
  					AD-18961
  2128	CUUGCUCAGGAC	2231	GUCCUGAGCAAG	3626	AD-19047, AD-18984,
  					AD-26773, AD-18971
  2129	UUGCUCAGGACA	2232	UGUCCUGAGCAA	3627	AD-19047, AD-18984,
  					AD-26773, AD-18971,
  					AD-18961
  2130	UGCUCAGGACAA	2233	UUGUCCUGAGCA	3628	AD-18984, AD-26773,
  					AD-18971, AD-18961
  2131	GCUCAGGACAAG	2234	CUUGUCCUGAGC	3629	AD-18984, AD-26773,
  					AD-18961
  2132	CUCAGGACAAGG	2235	CCUUGUCCUGAG	3630	AD-18984, AD-26773
  2133	UCAGGACAAGGA	2236	UCCUUGUCCUGA	3631	AD-18984, AD-26773
  2178	AGCUCCUCUGAC	2237	GUCAGAGGAGCU	3632	AD-26775, AD-26774
  2179	GCUCCUCUGACA	2238	UGUCAGAGGAGC	3633	AD-26775, AD-26774
  2180	CUCCUCUGACAG	2239	CUGUCAGAGGAG	3634	AD-26775, AD-26774
  2181	UCCUCUGACAGA	2240	UCUGUCAGAGGA	3635	AD-26775, AD-26774
  2182	CCUCUGACAGAG	2241	CUCUGUCAGAGG	3636	AD-26775, AD-26776
  2183	CUCUGACAGAGU	2242	ACUCUGUCAGAG	3637	AD-26776, AD-26774
  2184	UCUGACAGAGUU	2243	AACUCUGUCAGA	3638	AD-26775, AD-26776,
  					AD-26774
  2185	CUGACAGAGUUA	2244	UAACUCUGUCAG	3639	AD-26775, AD-26776
  2188	ACAGAGUUACUU	2245	AAGUAACUCUGU	3640	AD-26777, AD-26776
  2191	GAGUUACUUCAC	2246	GUGAAGUAACUC	3641	AD-26777, AD-19755
  2192	AGUUACUUCACU	2247	AGUGAAGUAACU	3642	AD-26777, AD-26778,
  					AD-19755
  2193	GUUACUUCACUC	2248	GAGUGAAGUAAC	3643	AD-26777, AD-26779,
  					AD-26778, AD-19755
  2194	UUACUUCACUCU	2249	AGAGUGAAGUAA	3644	AD-26777, AD-26779,
  					AD-19755
  2195	UACUUCACUCUA	2250	UAGAGUGAAGUA	3645	AD-26777, AD-26778,
  					AD-19755
  2196	ACUUCACUCUAG	2251	CUAGAGUGAAGU	3646	AD-26780, AD-26778,
  					AD-19755
  2197	CUUCACUCUAGG	2252	CCUAGAGUGAAG	3647	AD-26779, AD-26780,
  					AD-26778, AD-19755
  2198	UUCACUCUAGGA	2253	UCCUAGAGUGAA	3648	AD-26779, AD-26780,
  					AD-26778, AD-19755
  2199	UCACUCUAGGAA	2254	UUCCUAGAGUGA	3649	AD-26779, AD-26780,
  					AD-26778
  2200	CACUCUAGGAAU	2255	AUUCCUAGAGUG	3650	AD-26779, AD-26780
  2234	CUGCUGUUUUGU	2256	ACAAAACAGCAG	3651	AD-26782, AD-26781
  2235	UGCUGUUUUGUU	2257	AACAAAACAGCA	3652	AD-26782, AD-26781
  2236	GCUGUUUUGUUC	2258	GAACAAAACAGC	3653	AD-26782, AD-26781
  2237	CUGUUUUGUUCC	2259	GGAACAAAACAG	3654	AD-26782, AD-26781
  2238	UGUUUUGUUCCG	2260	CGGAACAAAACA	3655	AD-26782, AD-26781
  2239	GUUUUGUUCCGA	2261	UCGGAACAAAAC	3656	AD-26782, AD-26781
  2240	UUUUGUUCCGAA	2262	UUCGGAACAAAA	3657	AD-26782, AD-26781
  2256	UGAGGACAAGCC	2263	GGCUUGUCCUCA	3658	AD-26783, AD-26784
  2257	GAGGACAAGCCA	2264	UGGCUUGUCCUC	3659	AD-26783, AD-26784
  2258	AGGACAAGCCAC	2265	GUGGCUUGUCCU	3660	AD-26783, AD-26784
  2259	GGACAAGCCACA	2266	UGUGGCUUGUCC	3661	AD-26783, AD-26784
  2260	GACAAGCCACAA	2267	UUGUGGCUUGUC	3662	AD-26783, AD-26784
  2261	ACAAGCCACAAG	2268	CUUGUGGCUUGU	3663	AD-26784, AD-26785
  2262	CAAGCCACAAGA	2269	UCUUGUGGCUUG	3664	AD-26784, AD-26785
  2263	AAGCCACAAGAU	2270	AUCUUGUGGCUU	3665	AD-26784, AD-26785
  2264	AGCCACAAGAUU	2271	AAUCUUGUGGCU	3666	AD-26786, AD-26785
  2265	GCCACAAGAUUA	2272	UAAUCUUGUGGC	3667	AD-26786, AD-26785
  2266	CCACAAGAUUAC	2273	GUAAUCUUGUGG	3668	AD-26786, AD-26785
  2267	CACAAGAUUACA	2274	UGUAAUCUUGUG	3669	AD-26786, AD-26785
  2268	ACAAGAUUACAA	2275	UUGUAAUCUUGU	3670	AD-26786, AD-26785
  2271	AGAUUACAAGAA	2276	UUCUUGUAAUCU	3671	AD-26786, AD-26787
  2277	CAAGAAACGGCU	2277	AGCCGUUUCUUG	3672	AD-26788, AD-26787
  2278	AAGAAACGGCUU	2278	AAGCCGUUUCUU	3673	AD-26788, AD-26787
  2302	ACCAGCUCUCUC	2279	GAGAGAGCUGGU	3674	AD-26790, AD-26789
  2303	CCAGCUCUCUCU	2280	AGAGAGAGCUGG	3675	AD-26790, AD-26789
  2304	CAGCUCUCUCUU	2281	AAGAGAGAGCUG	3676	AD-26790, AD-26789
  2325	GCCAAUGGCUUG	2282	CAAGCCAUUGGC	3677	AD-18909, AD-18910
  2326	CCAAUGGCUUGG	2283	CCAAGCCAUUGG	3678	AD-18909, AD-18910,
  					AD-19080
  2327	CAAUGGCUUGGA	2284	UCCAAGCCAUUG	3679	AD-18909, AD-18947,
  					AD-18910, AD-19080
  2328	AAUGGCUUGGAA	2285	UUCCAAGCCAUU	3680	AD-18909, AD-19051,
  					AD-18947, AD-18910,
  					AD-19080
  2329	AUGGCUUGGAAU	2286	AUUCCAAGCCAU	3681	AD-18909, AD-19051,
  					AD-18947, AD-18978,
  					AD-18910
  2330	UGGCUUGGAAUG	2287	CAUUCCAAGCCA	3682	AD-18909, AD-19051,
  					AD-18947, AD-18978,
  					AD-19080
  2331	GGCUUGGAAUGA	2288	UCAUUCCAAGCC	3683	AD-18909, AD-19051,
  					AD-18947, AD-18978,
  					AD-18910, AD-19080
  2332	GCUUGGAAUGAG	2289	CUCAUUCCAAGC	3684	AD-19051, AD-18947,
  					AD-18978, AD-18910,
  					AD-19080
  2333	CUUGGAAUGAGA	2290	UCUCAUUCCAAG	3685	AD-19051, AD-18947,
  					AD-18978, AD-19080
  2334	UUGGAAUGAGAC	2291	GUCUCAUUCCAA	3686	AD-19051, AD-18947,
  					AD-18978
  2335	UGGAAUGAGACU	2292	AGUCUCAUUCCA	3687	AD-19051, AD-18978
  2370	UGCCCAGGGAGA	2293	UCUCCCUGGGCA	3688	AD-26677, AD-26791
  2371	GCCCAGGGAGAA	2294	UUCUCCCUGGGC	3689	AD-26677, AD-26791
  2374	CAGGGAGAACCC	2295	GGGUUCUCCCUG	3690	AD-26792, AD-26677
  2375	AGGGAGAACCCC	2296	GGGGUUCUCCCU	3691	AD-26793, AD-26677
  2376	GGGAGAACCCCU	2297	AGGGGUUCUCCC	3692	AD-26793, AD-26792
  2377	GGAGAACCCCUU	2298	AAGGGGUUCUCC	3693	AD-26793, AD-26792,
  					AD-26677
  2378	GAGAACCCCUUG	2299	CAAGGGGUUCUC	3694	AD-26793, AD-26792
  2379	AGAACCCCUUGG	2300	CCAAGGGGUUCU	3695	AD-26793, AD-26792
  2380	GAACCCCUUGGA	2301	UCCAAGGGGUUC	3696	AD-26793, AD-26792
  2381	AACCCCUUGGAU	2302	AUCCAAGGGGUU	3697	AD-26793, AD-26792
  2385	CCUUGGAUAUCG	2303	CGAUAUCCAAGG	3698	AD-26794, AD-19063
  2386	CUUGGAUAUCGC	2304	GCGAUAUCCAAG	3699	AD-26794, AD-19063
  2387	UUGGAUAUCGCC	2305	GGCGAUAUCCAA	3700	AD-18979, AD-26794,
  					AD-19063
  2388	UGGAUAUCGCCA	2306	UGGCGAUAUCCA	3701	AD-18979, AD-19001,
  					AD-26794, AD-19063
  2389	GGAUAUCGCCAG	2307	CUGGCGAUAUCC	3702	AD-18979, AD-18941,
  					AD-19001, AD-26794,
  					AD-19063
  2390	GAUAUCGCCAGG	2308	CCUGGCGAUAUC	3703	AD-18979, AD-18941,
  					AD-19001, AD-18900,
  					AD-26794, AD-19063
  2391	AUAUCGCCAGGA	2309	UCCUGGCGAUAU	3704	AD-18979, AD-18941,
  					AD-19001, AD-18900,
  					AD-26794
  2392	UAUCGCCAGGAU	2310	AUCCUGGCGAUA	3705	AD-18979, AD-18941,
  					AD-19001, AD-18900,
  					AD-26794, AD-26795
  2393	AUCGCCAGGAUG	2311	CAUCCUGGCGAU	3706	AD-18979, AD-18941,
  					AD-19001, AD-26795
  2394	UCGCCAGGAUGA	2312	UCAUCCUGGCGA	3707	AD-18979, AD-18941,
  					AD-19001, AD-18900,
  					AD-26795
  2395	CGCCAGGAUGAU	2313	AUCAUCCUGGCG	3708	AD-18941, AD-19001,
  					AD-18900, AD-26795
  2396	GCCAGGAUGAUC	2314	GAUCAUCCUGGC	3709	AD-18941, AD-26796,
  					AD-26795
  2397	CCAGGAUGAUCC	2315	GGAUCAUCCUGG	3710	AD-26796, AD-18900,
  					AD-26795, AD-26797
  2398	CAGGAUGAUCCU	2316	AGGAUCAUCCUG	3711	AD-26796, AD-26795,
  					AD-26797
  2399	AGGAUGAUCCUA	2317	UAGGAUCAUCCU	3712	AD-26796, AD-26795
  2400	GGAUGAUCCUAG	2318	CUAGGAUCAUCC	3713	AD-26796, AD-26797
  2401	GAUGAUCCUAGC	2319	GCUAGGAUCAUC	3714	AD-26796, AD-26798,
  					AD-26797
  2402	AUGAUCCUAGCU	2320	AGCUAGGAUCAU	3715	AD-26796, AD-26797
  2403	UGAUCCUAGCUA	2321	UAGCUAGGAUCA	3716	AD-26796, AD-26798,
  					AD-26797
  2404	GAUCCUAGCUAU	2322	AUAGCUAGGAUC	3717	AD-26798, AD-26797
  2405	AUCCUAGCUAUC	2323	GAUAGCUAGGAU	3718	AD-26799, AD-26798
  2406	UCCUAGCUAUCG	2324	CGAUAGCUAGGA	3719	AD-26799, AD-26800
  2407	CCUAGCUAUCGU	2325	ACGAUAGCUAGG	3720	AD-26799, AD-26798
  2408	CUAGCUAUCGUU	2326	AACGAUAGCUAG	3721	AD-26799, AD-26798,
  					AD-26800
  2409	UAGCUAUCGUUC	2327	GAACGAUAGCUA	3722	AD-26799, AD-26800
  2410	AGCUAUCGUUCU	2328	AGAACGAUAGCU	3723	AD-26799, AD-26800
  2411	GCUAUCGUUCUU	2329	AAGAACGAUAGC	3724	AD-26799, AD-26800
  2412	CUAUCGUUCUUU	2330	AAAGAACGAUAG	3725	AD-26799, AD-26800
  2419	UCUUUUCACUCU	2331	AGAGUGAAAAGA	3726	AD-18951, AD-26801
  2420	CUUUUCACUCUG	2332	CAGAGUGAAAAG	3727	AD-18951, AD-26802,
  					AD-26801
  2421	UUUUCACUCUGG	2333	CCAGAGUGAAAA	3728	AD-18951, AD-26803,
  					AD-26802, AD-26801
  2422	UUUCACUCUGGU	2334	ACCAGAGUGAAA	3729	AD-18951, AD-26802,
  					AD-26801
  2423	UUCACUCUGGUG	2335	CACCAGAGUGAA	3730	AD-18951, AD-26803,
  					AD-26801
  2424	UCACUCUGGUGG	2336	CCACCAGAGUGA	3731	AD-26803, AD-26802
  2425	CACUCUGGUGGA	2337	UCCACCAGAGUG	3732	AD-26803, AD-26801
  2426	ACUCUGGUGGAU	2338	AUCCACCAGAGU	3733	AD-26803, AD-26802,
  					AD-26801
  2427	CUCUGGUGGAUA	2339	UAUCCACCAGAG	3734	AD-26803, AD-26802
  2435	GAUAUGGCCAGG	2340	CCUGGCCAUAUC	3735	AD-26805, AD-26804
  2436	AUAUGGCCAGGA	2341	UCCUGGCCAUAU	3736	AD-26805, AD-26804
  2437	UAUGGCCAGGAU	2342	AUCCUGGCCAUA	3737	AD-26805, AD-26804
  2440	GGCCAGGAUGCC	2343	GGCAUCCUGGCC	3738	AD-26693, AD-26805
  2441	GCCAGGAUGCCU	2344	AGGCAUCCUGGC	3739	AD-26693, AD-26805
  2442	CCAGGAUGCCUU	2345	AAGGCAUCCUGG	3740	AD-26693, AD-26805
  2453	UGGGUAUGGACC	2346	GGUCCAUACCCA	3741	AD-26806, AD-26807
  2454	GGGUAUGGACCC	2347	GGGUCCAUACCC	3742	AD-26806, AD-26807
  2455	GGUAUGGACCCC	2348	GGGGUCCAUACC	3743	AD-26806, AD-26807
  2456	GUAUGGACCCCA	2349	UGGGGUCCAUAC	3744	AD-26806, AD-26807
  2457	UAUGGACCCCAU	2350	AUGGGGUCCAUA	3745	AD-26806, AD-26811,
  					AD-26807
  2458	AUGGACCCCAUG	2351	CAUGGGGUCCAU	3746	AD-26811, AD-26807
  2459	UGGACCCCAUGA	2352	UCAUGGGGUCCA	3747	AD-26811, AD-26807
  2460	GGACCCCAUGAU	2353	AUCAUGGGGUCC	3748	AD-26811, AD-26807,
  					AD-26812
  2461	GACCCCAUGAUG	2354	CAUCAUGGGGUC	3749	AD-26811, AD-26812
  2462	ACCCCAUGAUGG	2355	CCAUCAUGGGGU	3750	AD-26811, AD-26812
  2463	CCCCAUGAUGGA	2356	UCCAUCAUGGGG	3751	AD-26811, AD-26812
  2464	CCCAUGAUGGAA	2357	UUCCAUCAUGGG	3752	AD-26811, AD-26812
  2465	CCAUGAUGGAAC	2358	GUUCCAUCAUGG	3753	AD-26813, AD-26812
  2466	CAUGAUGGAACA	2359	UGUUCCAUCAUG	3754	AD-26813, AD-26812
  2467	AUGAUGGAACAU	2360	AUGUUCCAUCAU	3755	AD-26813, AD-26812
  2493	CCACCCUGGUGC	2361	GCACCAGGGUGG	3756	AD-26814, AD-26815
  2494	CACCCUGGUGCU	2362	AGCACCAGGGUG	3757	AD-26814, AD-26815
  2495	ACCCUGGUGCUG	2363	CAGCACCAGGGU	3758	AD-26814, AD-26815
  2496	CCCUGGUGCUGA	2364	UCAGCACCAGGG	3759	AD-26814, AD-26815,
  					AD-19057
  2497	CCUGGUGCUGAC	2365	GUCAGCACCAGG	3760	AD-19071, AD-26814,
  					AD-26815, AD-19057
  2498	CUGGUGCUGACU	2366	AGUCAGCACCAG	3761	AD-19071, AD-26814,
  					AD-26815, AD-18970,
  					AD-19057
  2499	UGGUGCUGACUA	2367	UAGUCAGCACCA	3762	AD-19071, AD-26814,
  					AD-26815, AD-18970,
  					AD-19057, AD-18892
  2500	GGUGCUGACUAU	2368	AUAGUCAGCACC	3763	AD-19071, AD-26815,
  					AD-18970, AD-19057,
  					AD-18892
  2501	GUGCUGACUAUC	2369	GAUAGUCAGCAC	3764	AD-19071, AD-18970,
  					AD-19057, AD-18892
  2502	UGCUGACUAUCC	2370	GGAUAGUCAGCA	3765	AD-19071, AD-26816,
  					AD-18970, AD-19057,
  					AD-18892
  2503	GCUGACUAUCCA	2371	UGGAUAGUCAGC	3766	AD-19071, AD-19042,
  					AD-26816, AD-18970,
  					AD-19057
  2504	CUGACUAUCCAG	2372	CUGGAUAGUCAG	3767	AD-19071, AD-19042,
  					AD-26816, AD-18970,
  					AD-18919, AD-18892
  2505	UGACUAUCCAGU	2373	ACUGGAUAGUCA	3768	AD-19042, AD-18944,
  					AD-18970, AD-18919,
  					AD-18892
  2506	GACUAUCCAGUU	2374	AACUGGAUAGUC	3769	AD-19042, AD-26816,
  					AD-18944, AD-18908,
  					AD-18919, AD-18892
  2507	ACUAUCCAGUUG	2375	CAACUGGAUAGU	3770	AD-19042, AD-26816,
  					AD-18967, AD-18944,
  					AD-18908, AD-18919
  2508	CUAUCCAGUUGA	2376	UCAACUGGAUAG	3771	AD-19042, AD-26816,
  					AD-18967, AD-18944,
  					AD-18908, AD-19077,
  					AD-18919
  2509	UAUCCAGUUGAU	2377	AUCAACUGGAUA	3772	AD-19042, AD-26816,
  					AD-18967, AD-18944,
  					AD-18908, AD-19077,
  					AD-18919
  2510	AUCCAGUUGAUG	2378	CAUCAACUGGAU	3773	AD-19042, AD-18967,
  					AD-18944, AD-18908,
  					AD-19077, AD-18919
  2511	UCCAGUUGAUGG	2379	CCAUCAACUGGA	3774	AD-18967, AD-18944,
  					AD-18908, AD-19077,
  					AD-18919
  2512	CCAGUUGAUGGG	2380	CCCAUCAACUGG	3775	AD-18967, AD-18944,
  					AD-18908, AD-19077
  2513	CAGUUGAUGGGC	2381	GCCCAUCAACUG	3776	AD-18967, AD-18908,
  					AD-19077
  2514	AGUUGAUGGGCU	2382	AGCCCAUCAACU	3777	AD-26817, AD-18967,
  					AD-19077
  2515	GUUGAUGGGCUG	2383	CAGCCCAUCAAC	3778	AD-26817, AD-19077
  2544	CCAGGACCUCAU	2384	AUGAGGUCCUGG	3779	AD-19073, AD-26818
  2545	CAGGACCUCAUG	2385	CAUGAGGUCCUG	3780	AD-19073, AD-26818
  2546	AGGACCUCAUGG	2386	CCAUGAGGUCCU	3781	AD-19073, AD-26818
  2547	GGACCUCAUGGA	2387	UCCAUGAGGUCC	3782	AD-19073, AD-26818
  2548	GACCUCAUGGAU	2388	AUCCAUGAGGUC	3783	AD-19073, AD-26818
  2580	CAAUCAGCUGGC	2389	GCCAGCUGAUUG	3784	AD-26819, AD-26820
  2581	AAUCAGCUGGCC	2390	GGCCAGCUGAUU	3785	AD-26819, AD-26820
  2582	AUCAGCUGGCCU	2391	AGGCCAGCUGAU	3786	AD-26819, AD-18989,
  					AD-26820
  2583	UCAGCUGGCCUG	2392	CAGGCCAGCUGA	3787	AD-18975, AD-26819,
  					AD-18989, AD-26820
  2584	CAGCUGGCCUGG	2393	CCAGGCCAGCUG	3788	AD-18975, AD-26819,
  					AD-18989, AD-26820
  2585	AGCUGGCCUGGU	2394	ACCAGGCCAGCU	3789	AD-18975, AD-19060,
  					AD-26819, AD-18989,
  					AD-26820
  2586	GCUGGCCUGGUU	2395	AACCAGGCCAGC	3790	AD-18975, AD-18898,
  					AD-26819, AD-18989,
  					AD-26820
  2587	CUGGCCUGGUUU	2396	AAACCAGGCCAG	3791	AD-18975, AD-19060,
  					AD-18898, AD-18989,
  					AD-26820
  2588	UGGCCUGGUUUG	2397	CAAACCAGGCCA	3792	AD-18975, AD-19059,
  					AD-19060, AD-18964,
  					AD-18898, AD-18989
  2589	GGCCUGGUUUGA	2398	UCAAACCAGGCC	3793	AD-18920, AD-19059,
  					AD-19060, AD-18964,
  					AD-18898, AD-18989
  2590	GCCUGGUUUGAU	2399	AUCAAACCAGGC	3794	AD-18975, AD-18920,
  					AD-19059, AD-19060,
  					AD-18964, AD-18898
  2591	CCUGGUUUGAUA	2400	UAUCAAACCAGG	3795	AD-18922, AD-19059,
  					AD-19060, AD-18907,
  					AD-18964, AD-18898
  2592	CUGGUUUGAUAC	2401	GUAUCAAACCAG	3796	AD-18922, AD-18920,
  					AD-19060, AD-18907,
  					AD-18964, AD-18898
  2593	UGGUUUGAUACU	2402	AGUAUCAAACCA	3797	AD-18905, AD-18922,
  					AD-18920, AD-18907,
  					AD-18964
  2594	GGUUUGAUACUG	2403	CAGUAUCAAACC	3798	AD-18905, AD-18920,
  					AD-26821, AD-18907,
  					AD-18964
  2595	GUUUGAUACUGA	2404	UCAGUAUCAAAC	3799	AD-18922, AD-18920,
  					AD-19059, AD-26821,
  					AD-18986
  2596	UUUGAUACUGAC	2405	GUCAGUAUCAAA	3800	AD-18905, AD-18922,
  					AD-18920, AD-26821,
  					AD-18907, AD-19066,
  					AD-18986
  2597	UUGAUACUGACC	2406	GGUCAGUAUCAA	3801	AD-18905, AD-26821,
  					AD-18907, AD-18986
  2598	UGAUACUGACCU	2407	AGGUCAGUAUCA	3802	AD-18905, AD-18999,
  					AD-18907, AD-18965,
  					AD-19066
  2599	GAUACUGACCUG	2408	CAGGUCAGUAUC	3803	AD-18905, AD-26821,
  					AD-18999, AD-18965,
  					AD-19066, AD-18986
  2600	AUACUGACCUGU	2409	ACAGGUCAGUAU	3804	AD-26822, AD-18905,
  					AD-18965, AD-19066,
  					AD-18986
  2601	UACUGACCUGUA	2410	UACAGGUCAGUA	3805	AD-26822, AD-26821,
  					AD-18999, AD-18965,
  					AD-19066, AD-18986
  2602	ACUGACCUGUAA	2411	UUACAGGUCAGU	3806	AD-26822, AD-18999,
  					AD-18965, AD-19066,
  					AD-18986
  2603	CUGACCUGUAAA	2412	UUUACAGGUCAG	3807	AD-26822, AD-18999,
  					AD-18965, AD-19066
  2604	UGACCUGUAAAU	2413	AUUUACAGGUCA	3808	AD-26822, AD-18999,
  					AD-18965, AD-26823
  2605	GACCUGUAAAUC	2414	GAUUUACAGGUC	3809	AD-26822, AD-26824,
  					AD-18999, AD-26823
  2606	ACCUGUAAAUCA	2415	UGAUUUACAGGU	3810	AD-26822, AD-26824,
  					AD-26825, AD-26823
  2607	CCUGUAAAUCAU	2416	AUGAUUUACAGG	3811	AD-26822, AD-26824,
  					AD-26825, AD-26823
  2608	CUGUAAAUCAUC	2417	GAUGAUUUACAG	3812	AD-26824, AD-26825,
  					AD-26823
  2609	UGUAAAUCAUCC	2418	GGAUGAUUUACA	3813	AD-26824, AD-26823
  2610	GUAAAUCAUCCU	2419	AGGAUGAUUUAC	3814	AD-26825, AD-26823
  2611	UAAAUCAUCCUU	2420	AAGGAUGAUUUA	3815	AD-26824, AD-26825,
  					AD-26823
  2612	AAAUCAUCCUUU	2421	AAAGGAUGAUUU	3816	AD-26824, AD-26825
  2628	GUAACAAUACAA	2422	UUGUAUUGUUAC	3817	AD-18933, AD-19053
  2629	UAACAAUACAAA	2423	UUUGUAUUGUUA	3818	AD-18933, AD-19053
  2630	AACAAUACAAAU	2424	AUUUGUAUUGUU	3819	AD-18933, AD-19053
  2631	ACAAUACAAAUG	2425	CAUUUGUAUUGU	3820	AD-18933, AD-19053
  2632	CAAUACAAAUGG	2426	CCAUUUGUAUUG	3821	AD-18933, AD-19053,
  					AD-25889
  2633	AAUACAAAUGGA	2427	UCCAUUUGUAUU	3822	AD-18933, AD-25889
  2634	AUACAAAUGGAU	2428	AUCCAUUUGUAU	3823	AD-18933, AD-25889
  2635	UACAAAUGGAUU	2429	AAUCCAUUUGUA	3824	AD-18933, AD-25889
  2636	ACAAAUGGAUUU	2430	AAAUCCAUUUGU	3825	AD-25890, AD-25889
  2637	CAAAUGGAUUUU	2431	AAAAUCCAUUUG	3826	AD-25890, AD-25889
  2638	AAAUGGAUUUUG	2432	CAAAAUCCAUUU	3827	AD-25890, AD-25889
  2648	UGGGAGUGACUC	2433	GAGUCACUCCCA	3828	AD-25892, AD-25891
  2649	GGGAGUGACUCA	2434	UGAGUCACUCCC	3829	AD-25892, AD-25891
  2650	GGAGUGACUCAA	2435	UUGAGUCACUCC	3830	AD-25892, AD-25891
  2651	GAGUGACUCAAG	2436	CUUGAGUCACUC	3831	AD-25892, AD-25891
  2652	AGUGACUCAAGA	2437	UCUUGAGUCACU	3832	AD-25892, AD-25891
  2653	GUGACUCAAGAA	2438	UUCUUGAGUCAC	3833	AD-25892, AD-25891
  2654	UGACUCAAGAAG	2439	CUUCUUGAGUCA	3834	AD-25892, AD-25891
  2663	AAGUGAAGAAUG	2440	CAUUCUUCACUU	3835	AD-25894, AD-25893
  2664	AGUGAAGAAUGC	2441	GCAUUCUUCACU	3836	AD-25894, AD-25938
  2665	GUGAAGAAUGCA	2442	UGCAUUCUUCAC	3837	AD-25893, AD-25938
  2666	UGAAGAAUGCAC	2443	GUGCAUUCUUCA	3838	AD-25894, AD-25893
  2667	GAAGAAUGCACA	2444	UGUGCAUUCUUC	3839	AD-25894, AD-25893,
  					AD-25938
  2668	AAGAAUGCACAA	2445	UUGUGCAUUCUU	3840	AD-25894, AD-25893,
  					AD-25938
  2669	AGAAUGCACAAG	2446	CUUGUGCAUUCU	3841	AD-25894, AD-25893,
  					AD-25938
  2670	GAAUGCACAAGA	2447	UCUUGUGCAUUC	3842	AD-25894, AD-25938
  2682	AUGGAUCACAAG	2448	CUUGUGAUCCAU	3843	AD-25940, AD-25939
  2683	UGGAUCACAAGA	2449	UCUUGUGAUCCA	3844	AD-25941, AD-25940,
  					AD-25939
  2684	GGAUCACAAGAU	2450	AUCUUGUGAUCC	3845	AD-25941, AD-25940,
  					AD-25942, AD-25939
  2685	GAUCACAAGAUG	2451	CAUCUUGUGAUC	3846	AD-25941, AD-25940,
  					AD-25942, AD-25939,
  					AD-25943
  2686	AUCACAAGAUGG	2452	CCAUCUUGUGAU	3847	AD-25941, AD-25940,
  					AD-25944, AD-25942,
  					AD-25939, AD-25943
  2687	UCACAAGAUGGA	2453	UCCAUCUUGUGA	3848	AD-25941, AD-25940,
  					AD-25944, AD-25942,
  					AD-25943
  2688	CACAAGAUGGAA	2454	UUCCAUCUUGUG	3849	AD-25941, AD-25944,
  					AD-25942, AD-25939,
  					AD-25943
  2689	ACAAGAUGGAAU	2455	AUUCCAUCUUGU	3850	AD-25941, AD-25940,
  					AD-25944, AD-25942,
  					AD-25943
  2690	CAAGAUGGAAUU	2456	AAUUCCAUCUUG	3851	AD-25941, AD-25944,
  					AD-25942, AD-25943
  2691	AAGAUGGAAUUU	2457	AAAUUCCAUCUU	3852	AD-25944, AD-25942,
  					AD-25943
  2692	AGAUGGAAUUUA	2458	UAAAUUCCAUCU	3853	AD-25944, AD-25943
  2693	GAUGGAAUUUAU	2459	AUAAAUUCCAUC	3854	AD-25944, AD-25895
  2694	AUGGAAUUUAUC	2460	GAUAAAUUCCAU	3855	AD-25895, AD-25896
  2695	UGGAAUUUAUCA	2461	UGAUAAAUUCCA	3856	AD-25895, AD-25896,
  					AD-25945
  2696	GGAAUUUAUCAA	2462	UUGAUAAAUUCC	3857	AD-25895, AD-25896,
  					AD-25897, AD-25945
  2697	GAAUUUAUCAAA	2463	UUUGAUAAAUUC	3858	AD-25895, AD-25896,
  					AD-25898, AD-25897,
  					AD-25945
  2698	AAUUUAUCAAAC	2464	GUUUGAUAAAUU	3859	AD-25895, AD-25899,
  					AD-25896, AD-25898,
  					AD-25945
  2699	AUUUAUCAAACC	2465	GGUUUGAUAAAU	3860	AD-25895, AD-25896,
  					AD-25898, AD-25897,
  					AD-25945
  2700	UUUAUCAAACCC	2466	GGGUUUGAUAAA	3861	AD-25895, AD-25899,
  					AD-25896, AD-25898,
  					AD-25897, AD-25945
  2701	UUAUCAAACCCU	2467	AGGGUUUGAUAA	3862	AD-25899, AD-25896,
  					AD-25897, AD-18929,
  					AD-25945
  2702	UAUCAAACCCUA	2468	UAGGGUUUGAUA	3863	AD-25899, AD-25898,
  					AD-25897, AD-18929,
  					AD-25945
  2703	AUCAAACCCUAG	2469	CUAGGGUUUGAU	3864	AD-18996, AD-25899,
  					AD-18915, AD-25898,
  					AD-25897, AD-18929
  2704	UCAAACCCUAGC	2470	GCUAGGGUUUGA	3865	AD-18996, AD-25899,
  					AD-18915, AD-25898,
  					AD-18929
  2705	CAAACCCUAGCC	2471	GGCUAGGGUUUG	3866	AD-18935, AD-18996,
  					AD-25899, AD-18915
  2706	AAACCCUAGCCU	2472	AGGCUAGGGUUU	3867	AD-18915, AD-18942,
  					AD-18929
  2707	AACCCUAGCCUU	2473	AAGGCUAGGGUU	3868	AD-18913, AD-18935,
  					AD-18996, AD-18915
  2708	ACCCUAGCCUUG	2474	CAAGGCUAGGGU	3869	AD-18913, AD-18996,
  					AD-18915, AD-18942,
  					AD-18929, AD-25946
  2709	CCCUAGCCUUGC	2475	GCAAGGCUAGGG	3870	AD-18913, AD-18935,
  					AD-18996, AD-25947,
  					AD-18915, AD-25946
  2710	CCUAGCCUUGCU	2476	AGCAAGGCUAGG	3871	AD-18913, AD-25948,
  					AD-18935, AD-25947,
  					AD-18915, AD-18942,
  					AD-25946
  2711	CUAGCCUUGCUU	2477	AAGCAAGGCUAG	3872	AD-18913, AD-25948,
  					AD-18935, AD-25949,
  					AD-25947, AD-18942,
  					AD-25946
  2712	UAGCCUUGCUUG	2478	CAAGCAAGGCUA	3873	AD-18913, AD-25948,
  					AD-18935, AD-25950,
  					AD-25947, AD-18942,
  					AD-25946
  2713	AGCCUUGCUUGU	2479	ACAAGCAAGGCU	3874	AD-18913, AD-25948,
  					AD-25951, AD-25949,
  					AD-25947, AD-18942,
  					AD-25946
  2714	GCCUUGCUUGUU	2480	AACAAGCAAGGC	3875	AD-18913, AD-25948,
  					AD-25951, AD-25950,
  					AD-25949, AD-25947,
  					AD-25946
  2715	CCUUGCUUGUUA	2481	UAACAAGCAAGG	3876	AD-25948, AD-25951,
  					AD-25950, AD-25949,
  					AD-25947, AD-25946
  2716	CUUGCUUGUUAA	2482	UUAACAAGCAAG	3877	AD-25948, AD-25951,
  					AD-25950, AD-25949,
  					AD-25947
  2717	UUGCUUGUUAAA	2483	UUUAACAAGCAA	3878	AD-25948, AD-25951,
  					AD-25950, AD-25949
  2718	UGCUUGUUAAAU	2484	AUUUAACAAGCA	3879	AD-25951, AD-25950,
  					AD-25949
  2719	GCUUGUUAAAUU	2485	AAUUUAACAAGC	3880	AD-25951, AD-25950
  2750	GAAUAUCUGUAA	2486	UUACAGAUAUUC	3881	AD-25900, AD-26900
  2751	AAUAUCUGUAAU	2487	AUUACAGAUAUU	3882	AD-25900, AD-26900,
  					AD-25901
  2752	AUAUCUGUAAUG	2488	CAUUACAGAUAU	3883	AD-25900, AD-25902,
  					AD-25901
  2753	UAUCUGUAAUGG	2489	CCAUUACAGAUA	3884	AD-25900, AD-25902,
  					AD-25901
  2754	AUCUGUAAUGGU	2490	ACCAUUACAGAU	3885	AD-25900, AD-25901
  2755	UCUGUAAUGGUA	2491	UACCAUUACAGA	3886	AD-25902, AD-25901
  2756	CUGUAAUGGUAC	2492	GUACCAUUACAG	3887	AD-25900, AD-25902,
  					AD-25901
  2757	UGUAAUGGUACU	2493	AGUACCAUUACA	3888	AD-25900, AD-25902
  2758	GUAAUGGUACUG	2494	CAGUACCAUUAC	3889	AD-25902, AD-25901
  2832	UUUAAGUCUCUC	2495	GAGAGACUUAAA	3890	AD-25903, AD-25904
  2833	UUAAGUCUCUCG	2496	CGAGAGACUUAA	3891	AD-25903, AD-25952,
  					AD-25904
  2834	UAAGUCUCUCGU	2497	ACGAGAGACUUA	3892	AD-25903, AD-25952,
  					AD-25904, AD-25953
  2835	AAGUCUCUCGUA	2498	UACGAGAGACUU	3893	AD-25954, AD-25903,
  					AD-25952, AD-25904,
  					AD-25953
  2836	AGUCUCUCGUAG	2499	CUACGAGAGACU	3894	AD-25954, AD-25903,
  					AD-25952, AD-25904,
  					AD-25953, AD-25905
  2837	GUCUCUCGUAGU	2500	ACUACGAGAGAC	3895	AD-25954, AD-25903,
  					AD-25952, AD-25904,
  					AD-25953
  2838	UCUCUCGUAGUG	2501	CACUACGAGAGA	3896	AD-25954, AD-25952,
  					AD-25904, AD-25953,
  					AD-25905
  2839	CUCUCGUAGUGU	2502	ACACUACGAGAG	3897	AD-25954, AD-25952,
  					AD-25904, AD-25953,
  					AD-25905
  2840	UCUCGUAGUGUU	2503	AACACUACGAGA	3898	AD-25954, AD-25952,
  					AD-25953, AD-25905
  2841	CUCGUAGUGUUA	2504	UAACACUACGAG	3899	AD-25954, AD-25955,
  					AD-25953, AD-25905
  2842	UCGUAGUGUUAA	2505	UUAACACUACGA	3900	AD-25954, AD-25906,
  					AD-25955, AD-25905
  2843	CGUAGUGUUAAG	2506	CUUAACACUACG	3901	AD-25907, AD-25906,
  					AD-25955
  2844	GUAGUGUUAAGU	2507	ACUUAACACUAC	3902	AD-25907, AD-25906,
  					AD-25955
  2845	UAGUGUUAAGUU	2508	AACUUAACACUA	3903	AD-25907, AD-25908,
  					AD-25906, AD-25955,
  					AD-25909
  2846	AGUGUUAAGUUA	2509	UAACUUAACACU	3904	AD-25907, AD-25908,
  					AD-25956, AD-25906,
  					AD-25955, AD-25909
  2847	GUGUUAAGUUAU	2510	AUAACUUAACAC	3905	AD-25907, AD-25908,
  					AD-25956, AD-25957,
  					AD-25906, AD-25955,
  					AD-25909
  2848	UGUUAAGUUAUA	2511	UAUAACUUAACA	3906	AD-25907, AD-25908,
  					AD-25956, AD-25957,
  					AD-25906, AD-25909
  2849	GUUAAGUUAUAG	2512	CUAUAACUUAAC	3907	AD-25907, AD-25908,
  					AD-25956, AD-25957,
  					AD-25906, AD-25909
  2850	UUAAGUUAUAGU	2513	ACUAUAACUUAA	3908	AD-25907, AD-25956,
  					AD-25957, AD-25909
  2851	UAAGUUAUAGUG	2514	CACUAUAACUUA	3909	AD-25908, AD-25956,
  					AD-25957, AD-25909
  2852	AAGUUAUAGUGA	2515	UCACUAUAACUU	3910	AD-25956, AD-25957,
  					AD-25909
  2853	AGUUAUAGUGAA	2516	UUCACUAUAACU	3911	AD-25956, AD-25957
  2871	UACAGCAAUUUC	2517	GAAAUUGCUGUA	3912	AD-26901, AD-25958
  2872	ACAGCAAUUUCU	2518	AGAAAUUGCUGU	3913	AD-26901, AD-25958
  2873	CAGCAAUUUCUA	2519	UAGAAAUUGCUG	3914	AD-26901, AD-25958
  2874	AGCAAUUUCUAA	2520	UUAGAAAUUGCU	3915	AD-26901, AD-25958
  2875	GCAAUUUCUAAU	2521	AUUAGAAAUUGC	3916	AD-26901, AD-25958
  2876	CAAUUUCUAAUU	2522	AAUUAGAAAUUG	3917	AD-26901, AD-25958
  2877	AAUUUCUAAUUU	2523	AAAUUAGAAAUU	3918	AD-26901, AD-25958
  2901	UAAUGGUGUAGA	2524	UCUACACCAUUA	3919	AD-18936, AD-19054
  2902	AAUGGUGUAGAA	2525	UUCUACACCAUU	3920	AD-18936, AD-19054
  2903	AUGGUGUAGAAC	2526	GUUCUACACCAU	3921	AD-18936, AD-19010,
  					AD-19054
  2904	UGGUGUAGAACA	2527	UGUUCUACACCA	3922	AD-18936, AD-19009,
  					AD-19010, AD-19054
  2905	GGUGUAGAACAC	2528	GUGUUCUACACC	3923	AD-18936, AD-19009,
  					AD-18939, AD-19054
  2906	GUGUAGAACACU	2529	AGUGUUCUACAC	3924	AD-18966, AD-19009,
  					AD-19010, AD-18939,
  					AD-19054
  2907	UGUAGAACACUA	2530	UAGUGUUCUACA	3925	AD-18966, AD-19009,
  					AD-18902, AD-19010,
  					AD-18939, AD-19054
  2908	GUAGAACACUAA	2531	UUAGUGUUCUAC	3926	AD-18966, AD-19009,
  					AD-18902, AD-19010,
  					AD-18939, AD-19054,
  					AD-19076
  2909	UAGAACACUAAU	2532	AUUAGUGUUCUA	3927	AD-18966, AD-19009,
  					AD-18902, AD-19010,
  					AD-18939, AD-19076
  2910	AGAACACUAAUU	2533	AAUUAGUGUUCU	3928	AD-18966, AD-19009,
  					AD-19010, AD-18939,
  					AD-19076
  2911	GAACACUAAUUC	2534	GAAUUAGUGUUC	3929	AD-18966, AD-18902,
  					AD-18914, AD-18939,
  					AD-19076
  2912	AACACUAAUUCA	2535	UGAAUUAGUGUU	3930	AD-18966, AD-18902,
  					AD-18914, AD-25911,
  					AD-19076
  2913	ACACUAAUUCAU	2536	AUGAAUUAGUGU	3931	AD-18966, AD-18902,
  					AD-18914, AD-25912,
  					AD-19076
  2914	CACUAAUUCAUA	2537	UAUGAAUUAGUG	3932	AD-18902, AD-18914,
  					AD-25912, AD-25911,
  					AD-26902
  2915	ACUAAUUCAUAA	2538	UUAUGAAUUAGU	3933	AD-18914, AD-25912,
  					AD-25911, AD-26903,
  					AD-26902, AD-19076
  2916	CUAAUUCAUAAU	2539	AUUAUGAAUUAG	3934	AD-18914, AD-25912,
  					AD-25911, AD-26903,
  					AD-26902
  2917	UAAUUCAUAAUC	2540	GAUUAUGAAUUA	3935	AD-26916, AD-25911,
  					AD-26903, AD-26902,
  					AD-26904
  2918	AAUUCAUAAUCA	2541	UGAUUAUGAAUU	3936	AD-26905, AD-26916,
  					AD-18914, AD-25912,
  					AD-25911, AD-26903,
  					AD-26902, AD-26904
  2919	AUUCAUAAUCAC	2542	GUGAUUAUGAAU	3937	AD-26905, AD-26916,
  					AD-25912, AD-25911,
  					AD-26903, AD-26902,
  					AD-26904
  2920	UUCAUAAUCACU	2543	AGUGAUUAUGAA	3938	AD-26905, AD-26916,
  					AD-25912, AD-26903,
  					AD-26902, AD-26904
  2921	UCAUAAUCACUC	2544	GAGUGAUUAUGA	3939	AD-26905, AD-26916,
  					AD-26903, AD-26902,
  					AD-26904
  2922	CAUAAUCACUCU	2545	AGAGUGAUUAUG	3940	AD-26905, AD-26916,
  					AD-26903, AD-26904
  2923	AUAAUCACUCUA	2546	UAGAGUGAUUAU	3941	AD-26905, AD-26916,
  					AD-26904
  2924	UAAUCACUCUAA	2547	UUAGAGUGAUUA	3942	AD-26905, AD-26904
  2938	AAUUGUAAUCUG	2548	CAGAUUACAAUU	3943	AD-25913, AD-26906
  2939	AUUGUAAUCUGA	2549	UCAGAUUACAAU	3944	AD-25913, AD-26906,
  					AD-25914
  2940	UUGUAAUCUGAA	2550	UUCAGAUUACAA	3945	AD-25913, AD-26906,
  					AD-25915, AD-25914
  2941	UGUAAUCUGAAU	2551	AUUCAGAUUACA	3946	AD-25916, AD-25913,
  					AD-26906, AD-25915,
  					AD-25914
  2942	GUAAUCUGAAUA	2552	UAUUCAGAUUAC	3947	AD-25916, AD-25913,
  					AD-26906, AD-25914
  2943	UAAUCUGAAUAA	2553	UUAUUCAGAUUA	3948	AD-26906, AD-25915,
  					AD-25914
  2944	AAUCUGAAUAAA	2554	UUUAUUCAGAUU	3949	AD-25916, AD-25913,
  					AD-26906, AD-25915,
  					AD-25914
  2945	AUCUGAAUAAAG	2555	CUUUAUUCAGAU	3950	AD-25916, AD-26906,
  					AD-25915, AD-25914
  2946	UCUGAAUAAAGU	2556	ACUUUAUUCAGA	3951	AD-25916, AD-25915,
  					AD-25914
  2947	CUGAAUAAAGUG	2557	CACUUUAUUCAG	3952	AD-25916, AD-25915
  2978	UUGUAUAAAAUA	2558	UAUUUUAUACAA	3953	AD-26908, AD-26907
  2979	UGUAUAAAAUAG	2559	CUAUUUUAUACA	3954	AD-26908, AD-26907,
  					AD-26909
  2980	GUAUAAAAUAGA	2560	UCUAUUUUAUAC	3955	AD-26908, AD-26909
  2981	UAUAAAAUAGAC	2561	GUCUAUUUUAUA	3956	AD-26908, AD-26910,
  					AD-26907, AD-26909
  2982	AUAAAAUAGACA	2562	UGUCUAUUUUAU	3957	AD-26910, AD-26911,
  					AD-26907, AD-26909
  2983	UAAAAUAGACAA	2563	UUGUCUAUUUUA	3958	AD-26908, AD-26910,
  					AD-26911, AD-26907,
  					AD-26909
  2984	AAAAUAGACAAA	2564	UUUGUCUAUUUU	3959	AD-26908, AD-26910,
  					AD-26912, AD-26911,
  					AD-26907, AD-26909
  2985	AAAUAGACAAAU	2565	AUUUGUCUAUUU	3960	AD-26908, AD-26912,
  					AD-26911, AD-26913,
  					AD-26909
  2986	AAUAGACAAAUA	2566	UAUUUGUCUAUU	3961	AD-26910, AD-26912,
  					AD-26911, AD-26913,
  					AD-26909
  2987	AUAGACAAAUAG	2567	CUAUUUGUCUAU	3962	AD-26910, AD-26912,
  					AD-26911, AD-26913
  2988	UAGACAAAUAGA	2568	UCUAUUUGUCUA	3963	AD-26912, AD-26911
  2989	AGACAAAUAGAA	2569	UUCUAUUUGUCU	3964	AD-26912, AD-26911,
  					AD-26913
  2990	GACAAAUAGAAA	2570	UUUCUAUUUGUC	3965	AD-25917, AD-26913
  2991	ACAAAUAGAAAA	2571	UUUUCUAUUUGU	3966	AD-26913, AD-25918
  2992	CAAAUAGAAAAU	2572	AUUUUCUAUUUG	3967	AD-25917, AD-25959,
  					AD-25918
  2993	AAAUAGAAAAUG	2573	CAUUUUCUAUUU	3968	AD-25917, AD-25959,
  					AD-26917, AD-25918
  2994	AAUAGAAAAUGG	2574	CCAUUUUCUAUU	3969	AD-25917, AD-26918,
  					AD-25959, AD-26917
  2995	AUAGAAAAUGGU	2575	ACCAUUUUCUAU	3970	AD-25917, AD-26918,
  					AD-25959, AD-26917,
  					AD-25918, AD-25960
  2996	UAGAAAAUGGUC	2576	GACCAUUUUCUA	3971	AD-25917, AD-26918,
  					AD-25959, AD-26917,
  					AD-25919, AD-25918,
  					AD-25960
  2997	AGAAAAUGGUCC	2577	GGACCAUUUUCU	3972	AD-25917, AD-26918,
  					AD-25920, AD-25959,
  					AD-26917, AD-25919,
  					AD-25918, AD-25960
  2998	GAAAAUGGUCCA	2578	UGGACCAUUUUC	3973	AD-26918, AD-25920,
  					AD-25959, AD-26917,
  					AD-25919, AD-25918,
  					AD-25960
  2999	AAAAUGGUCCAA	2579	UUGGACCAUUUU	3974	AD-26918, AD-25920,
  					AD-25959, AD-26917,
  					AD-25919, AD-25960
  3000	AAAUGGUCCAAU	2580	AUUGGACCAUUU	3975	AD-26918, AD-25920,
  					AD-26917, AD-25919,
  					AD-25960
  3001	AAUGGUCCAAUU	2581	AAUUGGACCAUU	3976	AD-26918, AD-25920,
  					AD-25919, AD-25960
  3002	AUGGUCCAAUUA	2582	UAAUUGGACCAU	3977	AD-25920, AD-25919,
  					AD-25960
  3003	UGGUCCAAUUAG	2583	CUAAUUGGACCA	3978	AD-25920, AD-25919
  3028	AUGCUUAAAAUA	2584	UAUUUUAAGCAU	3979	AD-18985, AD-18992
  3029	UGCUUAAAAUAA	2585	UUAUUUUAAGCA	3980	AD-18985, AD-18992
  3030	GCUUAAAAUAAG	2586	CUUAUUUUAAGC	3981	AD-18985, AD-18992
  3031	CUUAAAAUAAGC	2587	GCUUAUUUUAAG	3982	AD-18985, AD-18992,
  					AD-19081
  3032	UUAAAAUAAGCA	2588	UGCUUAUUUUAA	3983	AD-18985, AD-19081
  3033	UAAAAUAAGCAG	2589	CUGCUUAUUUUA	3984	AD-18985, AD-18992,
  					AD-19081, AD-19044
  3034	AAAAUAAGCAGG	2590	CCUGCUUAUUUU	3985	AD-18985, AD-18992,
  					AD-19081
  3035	AAAUAAGCAGGU	2591	ACCUGCUUAUUU	3986	AD-18985, AD-19044
  3036	AAUAAGCAGGUG	2592	CACCUGCUUAUU	3987	AD-18993, AD-19081,
  					AD-19044
  3037	AUAAGCAGGUGG	2593	CCACCUGCUUAU	3988	AD-18993, AD-18894,
  					AD-19081, AD-19044
  3038	UAAGCAGGUGGA	2594	UCCACCUGCUUA	3989	AD-19043, AD-18993,
  					AD-18894, AD-19044
  3039	AAGCAGGUGGAU	2595	AUCCACCUGCUU	3990	AD-19043, AD-18956,
  					AD-18993, AD-18894
  3040	AGCAGGUGGAUC	2596	GAUCCACCUGCU	3991	AD-19043, AD-18956,
  					AD-18993, AD-18894,
  					AD-19044, AD-18958
  3041	GCAGGUGGAUCU	2597	AGAUCCACCUGC	3992	AD-19043, AD-18956,
  					AD-18993, AD-18894,
  					AD-18958
  3042	CAGGUGGAUCUA	2598	UAGAUCCACCUG	3993	AD-19043, AD-18956,
  					AD-18894, AD-18969,
  					AD-18958, AD-19058
  3043	AGGUGGAUCUAU	2599	AUAGAUCCACCU	3994	AD-19069, AD-19043,
  					AD-18956, AD-18993,
  					AD-18894, AD-18969,
  					AD-18958, AD-19058
  3044	GGUGGAUCUAUU	2600	AAUAGAUCCACC	3995	AD-19069, AD-19043,
  					AD-18956, AD-18894,
  					AD-18969, AD-18958,
  					AD-19058
  3045	GUGGAUCUAUUU	2601	AAAUAGAUCCAC	3996	AD-19069, AD-19043,
  					AD-18956, AD-18969,
  					AD-18958, AD-19058
  3046	UGGAUCUAUUUC	2602	GAAAUAGAUCCA	3997	AD-19069, AD-18956,
  					AD-18969, AD-18958,
  					AD-19058
  3047	GGAUCUAUUUCA	2603	UGAAAUAGAUCC	3998	AD-19069, AD-18969,
  					AD-18958, AD-19058
  3048	GAUCUAUUUCAU	2604	AUGAAAUAGAUC	3999	AD-19069, AD-18969,
  					AD-19058
  3049	AUCUAUUUCAUG	2605	CAUGAAAUAGAU	4000	AD-19069, AD-19058
  3077	AUUUGGGAUAUG	2606	CAUAUCCCAAAU	4001	AD-25921, AD-25922
  3078	UUUGGGAUAUGU	2607	ACAUAUCCCAAA	4002	AD-25961, AD-25921,
  					AD-25922
  3079	UUGGGAUAUGUA	2608	UACAUAUCCCAA	4003	AD-25961, AD-25923,
  					AD-25921, AD-25922
  3080	UGGGAUAUGUAU	2609	AUACAUAUCCCA	4004	AD-25961, AD-25923,
  					AD-26914, AD-25921,
  					AD-25922
  3081	GGGAUAUGUAUG	2610	CAUACAUAUCCC	4005	AD-25961, AD-25923,
  					AD-26915, AD-26914,
  					AD-25921, AD-25922
  3082	GGAUAUGUAUGG	2611	CCAUACAUAUCC	4006	AD-25961, AD-25923,
  					AD-25924, AD-26915,
  					AD-26914, AD-25921,
  					AD-25922
  3083	GAUAUGUAUGGG	2612	CCCAUACAUAUC	4007	AD-25961, AD-25923,
  					AD-25924, AD-26915,
  					AD-25962, AD-26914,
  					AD-25921, AD-25922
  3084	AUAUGUAUGGGU	2613	ACCCAUACAUAU	4008	AD-25961, AD-25923,
  					AD-25924, AD-26915,
  					AD-25962, AD-26914,
  					AD-25922
  3085	UAUGUAUGGGUA	2614	UACCCAUACAUA	4009	AD-25961, AD-25923,
  					AD-25924, AD-26915,
  					AD-25962, AD-26914
  3086	AUGUAUGGGUAG	2615	CUACCCAUACAU	4010	AD-25923, AD-25924,
  					AD-26915, AD-25962,
  					AD-26914
  3087	UGUAUGGGUAGG	2616	CCUACCCAUACA	4011	AD-25924, AD-26915,
  					AD-25962, AD-26914
  3088	GUAUGGGUAGGG	2617	CCCUACCCAUAC	4012	AD-25924, AD-26915,
  					AD-25962
  3089	UAUGGGUAGGGU	2618	ACCCUACCCAUA	4013	AD-25924, AD-25962
  3093	GGUAGGGUAAAU	2619	AUUUACCCUACC	4014	AD-18998, AD-25963
  3094	GUAGGGUAAAUC	2620	GAUUUACCCUAC	4015	AD-18998, AD-25963,
  					AD-18995
  3095	UAGGGUAAAUCA	2621	UGAUUUACCCUA	4016	AD-18998, AD-25963,
  					AD-18995
  3096	AGGGUAAAUCAG	2622	CUGAUUUACCCU	4017	AD-18998, AD-25963,
  					AD-18995
  3097	GGGUAAAUCAGU	2623	ACUGAUUUACCC	4018	AD-18998, AD-25963,
  					AD-18981, AD-18995
  3098	GGUAAAUCAGUA	2624	UACUGAUUUACC	4019	AD-18921, AD-18998,
  					AD-25963, AD-18981,
  					AD-18995
  3099	GUAAAUCAGUAA	2625	UUACUGAUUUAC	4020	AD-18921, AD-18998,
  					AD-18981, AD-18995
  3100	UAAAUCAGUAAG	2626	CUUACUGAUUUA	4021	AD-18921, AD-18998,
  					AD-18981, AD-19050,
  					AD-18995
  3101	AAAUCAGUAAGA	2627	UCUUACUGAUUU	4022	AD-18921, AD-18968,
  					AD-18981, AD-19050
  3102	AAUCAGUAAGAG	2628	CUCUUACUGAUU	4023	AD-18921, AD-18968,
  					AD-18981, AD-19050,
  					AD-19005
  3103	AUCAGUAAGAGG	2629	CCUCUUACUGAU	4024	AD-18921, AD-18968,
  					AD-18981, AD-19050,
  					AD-18903, AD-19005
  3104	UCAGUAAGAGGU	2630	ACCUCUUACUGA	4025	AD-18921, AD-18968,
  					AD-18972, AD-18981,
  					AD-19050, AD-18903,
  					AD-19005
  3105	CAGUAAGAGGUG	2631	CACCUCUUACUG	4026	AD-18921, AD-18968,
  					AD-18972, AD-19050,
  					AD-18903, AD-19005
  3106	AGUAAGAGGUGU	2632	ACACCUCUUACU	4027	AD-18968, AD-19050,
  					AD-18903, AD-19005
  3107	GUAAGAGGUGUU	2633	AACACCUCUUAC	4028	AD-18972, AD-19050,
  					AD-18903, AD-19005
  3108	UAAGAGGUGUUA	2634	UAACACCUCUUA	4029	AD-18968, AD-18972,
  					AD-18903, AD-25964,
  					AD-19005
  3109	AAGAGGUGUUAU	2635	AUAACACCUCUU	4030	AD-18972, AD-18903,
  					AD-25964, AD-19005
  3110	AGAGGUGUUAUU	2636	AAUAACACCUCU	4031	AD-18972, AD-18903,
  					AD-25925, AD-25926,
  					AD-25964
  3111	GAGGUGUUAUUU	2637	AAAUAACACCUC	4032	AD-25925, AD-25926,
  					AD-25964
  3112	AGGUGUUAUUUG	2638	CAAAUAACACCU	4033	AD-25927, AD-25925,
  					AD-25926, AD-25964
  3113	GGUGUUAUUUGG	2639	CCAAAUAACACC	4034	AD-25927, AD-25926,
  					AD-25964
  3114	GUGUUAUUUGGA	2640	UCCAAAUAACAC	4035	AD-25927, AD-25925,
  					AD-25926, AD-25964
  3115	UGUUAUUUGGAA	2641	UUCCAAAUAACA	4036	AD-25925, AD-25926,
  					AD-25964
  3116	GUUAUUUGGAAC	2642	GUUCCAAAUAAC	4037	AD-25927, AD-25925,
  					AD-25926
  3117	UUAUUUGGAACC	2643	GGUUCCAAAUAA	4038	AD-25927, AD-25926
  3123	GGAACCUUGUUU	2644	AAACAAGGUUCC	4039	AD-25929, AD-25928
  3124	GAACCUUGUUUU	2645	AAAACAAGGUUC	4040	AD-25930, AD-25928
  3125	AACCUUGUUUUG	2646	CAAAACAAGGUU	4041	AD-25930, AD-25929,
  					AD-25928
  3126	ACCUUGUUUUGG	2647	CCAAAACAAGGU	4042	AD-25930, AD-25929
  3127	CCUUGUUUUGGA	2648	UCCAAAACAAGG	4043	AD-25930, AD-25929,
  					AD-25928
  3128	CUUGUUUUGGAC	2649	GUCCAAAACAAG	4044	AD-25930, AD-25929,
  					AD-25928
  3129	UUGUUUUGGACA	2650	UGUCCAAAACAA	4045	AD-25929, AD-25928
  3130	UGUUUUGGACAG	2651	CUGUCCAAAACA	4046	AD-25930, AD-25929
  3131	GUUUUGGACAGU	2652	ACUGUCCAAAAC	4047	AD-25930, AD-25931
  3132	UUUUGGACAGUU	2653	AACUGUCCAAAA	4048	AD-25932, AD-25931
  3133	UUUGGACAGUUU	2654	AAACUGUCCAAA	4049	AD-25932, AD-26919,
  					AD-25931
  3134	UUGGACAGUUUA	2655	UAAACUGUCCAA	4050	AD-25933, AD-26919,
  					AD-25931
  3135	UGGACAGUUUAC	2656	GUAAACUGUCCA	4051	AD-25933, AD-25932,
  					AD-26919, AD-25931
  3136	GGACAGUUUACC	2657	GGUAAACUGUCC	4052	AD-25933, AD-25932,
  					AD-25931
  3137	GACAGUUUACCA	2658	UGGUAAACUGUC	4053	AD-25932, AD-26919,
  					AD-25931
  3138	ACAGUUUACCAG	2659	CUGGUAAACUGU	4054	AD-25933, AD-25932,
  					AD-26919, AD-25931
  3139	CAGUUUACCAGU	2660	ACUGGUAAACUG	4055	AD-25933, AD-25932,
  					AD-26919
  3140	AGUUUACCAGUU	2661	AACUGGUAAACU	4056	AD-25933, AD-26919
  3145	ACCAGUUGCCUU	2662	AAGGCAACUGGU	4057	AD-18940, AD-18916
  3146	CCAGUUGCCUUU	2663	AAAGGCAACUGG	4058	AD-18940, AD-18906,
  					AD-18916
  3147	CAGUUGCCUUUU	2664	AAAAGGCAACUG	4059	AD-18940, AD-18906,
  					AD-18916
  3148	AGUUGCCUUUUA	2665	UAAAAGGCAACU	4060	AD-18940, AD-19075,
  					AD-18916
  3149	GUUGCCUUUUAU	2666	AUAAAAGGCAAC	4061	AD-19075, AD-18906,
  					AD-18916
  3150	UUGCCUUUUAUC	2667	GAUAAAAGGCAA	4062	AD-18940, AD-19075,
  					AD-18906, AD-18916
  3151	UGCCUUUUAUCC	2668	GGAUAAAAGGCA	4063	AD-18940, AD-19075,
  					AD-18906, AD-18916
  3152	GCCUUUUAUCCC	2669	GGGAUAAAAGGC	4064	AD-18906, AD-18916
  3153	CCUUUUAUCCCA	2670	UGGGAUAAAAGG	4065	AD-26017, AD-19075,
  					AD-18906, AD-18997
  3154	CUUUUAUCCCAA	2671	UUGGGAUAAAAG	4066	AD-26017, AD-19075,
  					AD-18997
  3155	UUUUAUCCCAAA	2672	UUUGGGAUAAAA	4067	AD-26017, AD-18997
  3156	UUUAUCCCAAAG	2673	CUUUGGGAUAAA	4068	AD-26017, AD-18997
  3157	UUAUCCCAAAGU	2674	ACUUUGGGAUAA	4069	AD-26017, AD-18997
  3158	UAUCCCAAAGUU	2675	AACUUUGGGAUA	4070	AD-26017, AD-18997,
  					AD-18988
  3159	AUCCCAAAGUUG	2676	CAACUUUGGGAU	4071	AD-18997, AD-18988
  3160	UCCCAAAGUUGU	2677	ACAACUUUGGGA	4072	AD-19067, AD-18997,
  					AD-18988
  3161	CCCAAAGUUGUU	2678	AACAACUUUGGG	4073	AD-19067, AD-19083
  3162	CCAAAGUUGUUG	2679	CAACAACUUUGG	4074	AD-19083, AD-18988
  3163	CAAAGUUGUUGU	2680	ACAACAACUUUG	4075	AD-19067, AD-19083,
  					AD-19049, AD-18988
  3164	AAAGUUGUUGUA	2681	UACAACAACUUU	4076	AD-19067, AD-19083,
  					AD-18952, AD-19049,
  					AD-18988
  3165	AAGUUGUUGUAA	2682	UUACAACAACUU	4077	AD-19067, AD-19083,
  					AD-18957, AD-18952,
  					AD-19049, AD-18988
  3166	AGUUGUUGUAAC	2683	GUUACAACAACU	4078	AD-19067, AD-19083,
  					AD-18957, AD-18952,
  					AD-19049
  3167	GUUGUUGUAACC	2684	GGUUACAACAAC	4079	AD-19067, AD-19083,
  					AD-18957, AD-25934,
  					AD-18952, AD-19049
  3168	UUGUUGUAACCU	2685	AGGUUACAACAA	4080	AD-19083, AD-18957,
  					AD-25934, AD-18952,
  					AD-25935, AD-19049
  3169	UGUUGUAACCUG	2686	CAGGUUACAACA	4081	AD-18957, AD-25934,
  					AD-18952, AD-26018,
  					AD-25935, AD-19049
  3170	GUUGUAACCUGC	2687	GCAGGUUACAAC	4082	AD-26019, AD-18957,
  					AD-25934, AD-18952,
  					AD-26018, AD-25935,
  					AD-19049
  3171	UUGUAACCUGCU	2688	AGCAGGUUACAA	4083	AD-26019, AD-18957,
  					AD-25936, AD-25934,
  					AD-18952, AD-26018,
  					AD-25935
  3172	UGUAACCUGCUG	2689	CAGCAGGUUACA	4084	AD-26019, AD-18957,
  					AD-25936, AD-25934,
  					AD-26018, AD-25935
  3173	GUAACCUGCUGU	2690	ACAGCAGGUUAC	4085	AD-26019, AD-25936,
  					AD-25934, AD-26018
  3174	UAACCUGCUGUG	2691	CACAGCAGGUUA	4086	AD-26019, AD-25936,
  					AD-25934, AD-26018,
  					AD-25935
  3175	AACCUGCUGUGA	2692	UCACAGCAGGUU	4087	AD-26019, AD-25936,
  					AD-26018, AD-25935
  3176	ACCUGCUGUGAU	2693	AUCACAGCAGGU	4088	AD-26019, AD-25936,
  					AD-26018
  3177	CCUGCUGUGAUA	2694	UAUCACAGCAGG	4089	AD-26019, AD-25936
  3197	CAAGAGAAAAUG	2695	CAUUUUCUCUUG	4090	AD-26020, AD-25937
  3198	AAGAGAAAAUGC	2696	GCAUUUUCUCUU	4091	AD-26020, AD-26021,
  					AD-25937
  3199	AGAGAAAAUGCG	2697	CGCAUUUUCUCU	4092	AD-26020, AD-26021
  3200	GAGAAAAUGCGG	2698	CCGCAUUUUCUC	4093	AD-26020, AD-26021
  3201	AGAAAAUGCGGU	2699	ACCGCAUUUUCU	4094	AD-26020, AD-26021
  3202	GAAAAUGCGGUU	2700	AACCGCAUUUUC	4095	AD-26020, AD-26021
  3203	AAAAUGCGGUUA	2701	UAACCGCAUUUU	4096	AD-26020, AD-26021
  3204	AAAUGCGGUUAU	2702	AUAACCGCAUUU	4097	AD-26020, AD-26021
  3220	AAUGGUUCAGAA	2703	UUCUGAACCAUU	4098	AD-18960, AD-18987
  3221	AUGGUUCAGAAU	2704	AUUCUGAACCAU	4099	AD-18960, AD-18987,
  					AD-19008
  3222	UGGUUCAGAAUU	2705	AAUUCUGAACCA	4100	AD-18960, AD-18987,
  					AD-19008
  3223	GGUUCAGAAUUA	2706	UAAUUCUGAACC	4101	AD-18980, AD-18987,
  					AD-19008
  3224	GUUCAGAAUUAA	2707	UUAAUUCUGAAC	4102	AD-18960, AD-18987,
  					AD-19008
  3225	UUCAGAAUUAAA	2708	UUUAAUUCUGAA	4103	AD-18960, AD-18980,
  					AD-19008
  3226	UCAGAAUUAAAC	2709	GUUUAAUUCUGA	4104	AD-18960, AD-18980,
  					AD-18987, AD-19008
  3227	CAGAAUUAAACU	2710	AGUUUAAUUCUG	4105	AD-18980, AD-18987,
  					AD-19008
  3228	AGAAUUAAACUU	2711	AAGUUUAAUUCU	4106	AD-18980, AD-19008
  3229	GAAUUAAACUUU	2712	AAAGUUUAAUUC	4107	AD-18980, AD-19007
  3230	AAUUAAACUUUU	2713	AAAAGUUUAAUU	4108	AD-18980, AD-19007

Example 2
• Synthesis of Beta-Catenin RNAi Agent Sequences
• Beta-Catenin RNAi Agent Sequence Selection
• 479 sense and 479 anti-sense CTNNB1-derived RNAi agent oligos listed herein are synthesized and formed into duplexes.
• Synthesis of Beta-Catenin Sequences
• Synthesis:
• Beta-Catenin sequences are synthesized on MerMade 192 synthesizer at 1 μmol scale.
• 958 single strand sequences (corresponding to 479 RNAi agent duplexes) are synthesized for the human Beta-Catenin gene. For all the sequences, ‘endolight’ chemistry is applied as detailed below.
• • All pyrimidines (cytosine and uridine) in the sense strand are replaced with corresponding 2′-O-Methyl bases (2′ O-Methyl C and 2′-O-Methyl U)
  • In the anti-sense strand, pyrimidines (C and U) adjacent to (towards 5′ position) ribo A nucleoside are replaced with their corresponding 2-O-Methyl nucleosides
  • A two base dTdT extension at 3′ end of both sense and anti-sense sequences is introduced. This two base overhang has a phosphodiester linkage
  • The sequence file is converted to a text file to make it compatible for loading in the MerMade 192 synthesis software
• The synthesis of Beta-Catenin sequences uses solid supported oligonucleotide synthesis using phosphoramidite chemistry
• The synthesis of the above sequences is performed at 1 μm scale in 96-well plates and 192 sequences are made per run. The amidite solutions are prepared at 0.1M concentration and ethyl thio tetrazole (0.6M in acetonitrile) is used as activator.
• Cleavage and De-Protection:
• The synthesized sequences are cleaved and de-protected in 96-well plates, using methylamine in the first step and triethylamine³HF in the second step. The crude sequences thus obtained are precipitated using acetone: ethanol mix and the pellet is re-suspended in 0.02M sodium acetate buffer. Samples from each sequence are analyzed by LC-MS and the resulting mass data confirms the identity of the sequences. A selected set of samples are also analyzed by IEX chromatography.
• Purification:
• Next step in the process is purification. All sequences are purified on AKTA explorer purification system using Source 15Q column Purification is performed using a column and in-line buffer heater set at 60° C. A single peak corresponding to the full length sequence is collected in the eluent and is subsequently analyzed for purity by ion exchange chromatography.
• The purified sequences are desalted on a Sephadex G25 column using AKTA purifier. The desalted Beta-Catenin sequences are analyzed for concentration and purity. The single strands are then annealed to form RNAi agent duplexes. Each duplex is made at a concentration of 10 μM in 1×PBS.
• A detailed list of Beta-Catenin single strands and duplexes are shown herein, in Example 1, above. The duplexes are used in in vitro screening to test their ability to knock down Beta-Catenin gene level, Example 3, below.
Example 3
• In Vitro Screening of Beta-Catenin RNAi Agents
• In Vitro Screening:
• RNAi agents listed herein (Example 1) and synthesized as described in Example 2, are tested for activity in vitro.
• Cell Culture and Transfections:
• HeLa cells (ATCC, Manassas, Va.) are grown to near confluence at 37° C. in an atmosphere of 5% CO₂in Eagle's Minimum Essential Medium (EMEM, ATCC) supplemented with 10% FBS, streptomycin, and glutamine (ATCC) before being released from the plate by trypsinization. Reverse transfection is carried out by adding 5 μl of Opti-MEM to 5 μl of RNAi agent duplexes per well into a 96-well plate along with 10 μl of Opti-MEM plus 0.2 μl of Lipofectamine RNAiMax per well (Invitrogen, Carlsbad, Calif. cat #13778-150) and incubated at room temperature for 15 minutes. For assays performed at 24 hours, 80 μl of complete growth media without antibiotic containing ˜2×10⁴HeLa cells are then added to the RNAi agent mixture. For assays performed at 120 hours, 80 μl of complete growth media without antibiotic containing ˜2×10⁴HeLa cells are then added to the RNAi agent mixture. Cells are incubated for either 24 or 48 hours prior to RNA purification. Single dose experiments are performed at 10 nM and in some cases 0.1 nM final duplex concentration and dose response experiments are done at 10, 1, 0.5, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, 0.0001, 0.00005, 0.00001 nM final duplex concentration.
• Total RNA Isolation Using MagMAX-96 Total RNA Isolation Kit (Applied Biosystem, Foster City Calif., Part #: AM1830):
• Cells are harvested and lysed in 140 μl of Lysis/Binding Solution then mixed for 1 minute at 850 rpm using and Eppendorf Thermomixer (the mixing speed is the same throughout the process). Twenty micro liters of magnetic beads and Lysis/Binding Enhancer mixture are added into cell-lysate and mixed for 5 minutes. Magnetic beads are captured using magnetic stand and the supernatant is removed without disturbing the beads. After removing supernatant, magnetic beads are washed with Wash Solution 1 (isopropanol added) and mixed for 1 minute. Beads are captured again and supernatant removed. Beads are then washed with 150 μl Wash Solution 2 (Ethanol added), captured and supernatant is removed. 50 μl of DNase mixture (MagMax turbo DNase Buffer and Turbo DNase) is then added to the beads and they are mixed for 10 to 15 minutes. After mixing, 100 μl of RNA Rebinding Solution is added and mixed for 3 minutes. Supernatant is removed and magnetic beads are washed again with 150 μl Wash Solution 2 and mixed for 1 minute and supernatant is removed completely. The magnetic beads are mixed for 2 minutes to dry before RNA is eluted with 50 μl of water.
• cDNA Synthesis Using ABI High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, Calif., Cat #4368813):
• A master mix of 2 μl 10× Buffer, 0.8 μl 25×dNTPs, 2 μl Random primers, 1 μl Reverse Transcriptase, 1 μl RNase inhibitor and 3.2 μl of H₂O per reaction are added into 10 μl total RNA. cDNA is generated using a Bio-Rad C-1000 or S-1000 thermal cycler (Hercules, Calif.) through the following steps: 25° C. 10 min, 37° C. 120 min, 85° C. 5 sec, 4° C. hold.
• Real Time PCR:
• 2 μl of cDNA are added to a master mix containing 1 μl 18S TaqMan Probe (Applied Biosystems Cat #4319413E), 1 ul β-catenin TaqMan probe (Applied Biosystems cat # HS00170025_m1) and 10 μl TaqMan Universal PCR Master Mix (Applied Biosystems Cat #4324018) per well in a MicroAmp Optical 96 well plate (Applied Biosystems cat #4326659). Real time PCR is done in an ABI 7900HT Real Time PCR system (Applied Biosystems) using the ΔΔCt(RQ) assay. Each duplex is tested in two independent transfections and each transfections is assayed in duplicate, unless otherwise noted in the summary tables.
• Real time data are analyzed using the ΔΔCt method and normalized to assays performed with cells transfected with 10 nM AD-1955 (a control RNAi agent that does not bind to Beta-Catenin) to calculate relative fold-change.
• The results are shown below. Table 5 shows the results of experiments performed at 0.1 or 10 nM final duplex concentration for single dose screens with each of the Beta-Catenin duplexes. The “Residual Gene Activity” (Fold-Change) indicates the residual gene level, at 10 nm or 0.1 nM. Thus, for AD-18892, a “Residual Gene Activity” at 10 nM at 24 hr of 0.054 indicates 5.4% remaining gene activity, or 94.6% gene knock-down. The Avg. EC50 (nM) indicates the estimated EC50 (concentration estimated to give 50% gene knock-down in HeLa cells), as calculated from available data collected at 10 nM, 1 nM, 0.1 nM, 0.01 nM, and 0.001 nM. “NA” indicates data is not available.

• TABLE 5
  Analysis of RNAi agents to Beta-Catenin

  			Residual	Residual
  	Sense		Gene	Gene
  	SEQ	Anti-sense	Activity	Activity	Avg.
  	ID	SEQ ID	10 nM	0.1 nM	EC50
  Duplex	NO:	NO:	24 hr	120 hr	(nM)

  AD-18892	1	6497	0.054	0.47	NA
  AD-18893	2	661	0.026	NA	0.008
  AD-18894	3	662	0.068	NA	0.005
  AD-18895	4	663	0.466	NA	NA
  AD-18896	5	664	0.244	NA	NA
  AD-18897	6	665	0.054	NA	0.028
  AD-18898	7	666	0.903	NA	NA
  AD-18899	8	667	0.301	NA	NA
  AD-18900	9	668	1.157	NA	NA
  AD-18901	10	669	0.359	NA	NA
  AD-18902	11	670	0.058	NA	0.005
  AD-18903	12	671	0.052	NA	0.002
  AD-18904	13	672	0.690	NA	NA
  AD-18905	14	673	0.198	NA	1.260
  AD-18906	15	674	0.248	NA	NA
  AD-18907	16	675	0.379	NA	NA
  AD-18908	17	676	0.157	NA	NA
  AD-18909	18	677	0.441	NA	NA
  AD-18910	19	678	0.385	NA	NA
  AD-18911	20	679	0.186	NA	1.664
  AD-18912	21	680	0.221	NA	NA
  AD-18913	22	681	0.124	NA	0.018
  AD-18914	23	682	0.058	NA	0.002
  AD-18915	24	683	0.242	NA	NA
  AD-18916	25	684	0.530	NA	NA
  AD-18917	26	685	0.527	0.66	NA
  AD-18918	27	686	1.161	NA	NA
  AD-18919	28	687	0.387	NA	NA
  AD-18920	29	688	1.124	NA	NA
  AD-18921	30	689	0.752	NA	NA
  AD-18922	31	690	0.587	NA	NA
  AD-18923	32	691	0.773	NA	NA
  AD-18925	33	692	0.738	NA	NA
  AD-18926	34	693	0.193	NA	0.033
  AD-18927	35	694	0.091	NA	0.764
  AD-18928	36	695	0.228	NA	NA
  AD-18929	37	696	0.069	NA	NA
  AD-18930	38	697	0.428	NA	NA
  AD-18931	39	698	1.195	NA	NA
  AD-18932	40	699	0.876	NA	NA
  AD-18933	41	700	0.047	NA	0.001
  AD-18934	42	701	0.651	NA	NA
  AD-18935	43	702	0.419	NA	NA
  AD-18936	44	703	0.125	NA	0.158
  AD-18937	45	704	0.839	NA	NA
  AD-18938	46	705	0.436	NA	NA
  AD-18939	47	706	0.068	NA	0.011
  AD-18940	48	707	0.515	NA	NA
  AD-18941	49	708	0.421	NA	NA
  AD-18942	50	709	1.397	NA	NA
  AD-18943	51	710	0.990	NA	NA
  AD-18944	52	711	0.550	NA	NA
  AD-18945	53	712	0.193	NA	0.780
  AD-18946	54	713	0.086	0.47	NA
  AD-18947	55	714	0.397	NA	NA
  AD-18948	56	715	0.885	NA	NA
  AD-18949	57	716	0.863	NA	NA
  AD-18950	58	717	0.103	NA	0.145
  AD-18951	59	718	0.184	NA	0.519
  AD-18952	60	719	0.382	NA	NA
  AD-18953	61	720	1.349	NA	NA
  AD-18954	62	721	0.766	NA	NA
  AD-18955	63	722	0.649	0.64	NA
  AD-18956	64	723	0.240	NA	NA
  AD-18957	65	724	1.198	NA	NA
  AD-18958	66	725	0.083	NA	0.012
  AD-18959	67	726	0.713	NA	NA
  AD-18960	68	727	0.188	NA	0.310
  AD-18961	69	728	0.105	NA	0.209
  AD-18962	70	729	0.942	NA	NA
  AD-18963	71	730	0.037	0.37	0.049
  AD-18964	72	731	0.907	NA	NA
  AD-18965	73	732	0.440	0.48	NA
  AD-18966	74	733	0.042	NA	0.000
  AD-18967	75	734	0.695	NA	NA
  AD-18968	76	735	0.158	NA	0.134
  AD-18969	77	736	0.073	NA	0.004
  AD-18970	78	737	0.810	NA	NA
  AD-18971	79	738	0.336	NA	NA
  AD-18972	80	739	0.332	NA	NA
  AD-18973	81	740	0.707	NA	NA
  AD-18974	82	741	0.038	NA	0.007
  AD-18975	83	742	0.184	0.73	NA
  AD-18976	84	743	0.094	NA	0.118
  AD-18977	85	744	0.965	NA	NA
  AD-18978	86	745	0.848	NA	NA
  AD-18979	87	746	0.375	NA	NA
  AD-18980	88	747	0.052	NA	NA
  AD-18981	89	748	0.090	NA	0.004
  AD-18982	90	749	0.156	NA	0.156
  AD-18983	91	750	0.026	0.23	0.070
  AD-18984	92	751	0.913	NA	NA
  AD-18985	93	752	0.578	NA	NA
  AD-18986	94	753	0.073	NA	0.003
  AD-18987	95	754	0.626	NA	NA
  AD-18988	96	755	0.379	NA	NA
  AD-18989	97	756	0.879	NA	NA
  AD-18990	98	757	0.299	NA	NA
  AD-18991	99	758	0.112	NA	0.454
  AD-18992	100	759	1.171	NA	NA
  AD-18993	101	760	0.802	NA	NA
  AD-18994	102	761	0.071	NA	0.313
  AD-18995	103	762	0.096	NA	0.006
  AD-18996	104	763	0.450	NA	NA
  AD-18997	105	764	0.226	NA	NA
  AD-18998	106	765	0.279	NA	NA
  AD-18999	107	766	0.337	NA	NA
  AD-19000	108	767	0.134	NA	0.347
  AD-19001	109	768	0.470	0.71	NA
  AD-19002	110	769	0.619	NA	NA
  AD-19003	111	770	0.610	NA	NA
  AD-19004	112	771	0.066	NA	0.007
  AD-19005	113	772	0.274	NA	NA
  AD-19006	114	773	0.139	NA	0.994
  AD-19007	115	774	0.655	NA	NA
  AD-19008	116	775	0.088	NA	0.001
  AD-19009	117	776	0.066	NA	0.000
  AD-19010	118	777	0.227	NA	NA
  AD-19011	119	778	0.721	NA	NA
  AD-19012	120	779	0.175	NA	0.181
  AD-19042	121	780	0.283	NA	NA
  AD-19043	122	781	0.131	NA	0.006
  AD-19044	123	782	0.333	NA	NA
  AD-19045	124	783	0.553	NA	NA
  AD-19046	125	784	0.947	NA	NA
  AD-19047	126	785	0.774	NA	NA
  AD-19048	127	786	0.838	NA	NA
  AD-19049	128	787	0.938	NA	NA
  AD-19050	129	788	0.070	NA	0.001
  AD-19051	130	789	0.551	NA	NA
  AD-19052	131	790	0.818	NA	NA
  AD-19053	132	791	0.364	NA	NA
  AD-19054	133	792	0.075	NA	0.002
  AD-19055	134	793	0.210	NA	NA
  AD-19056	135	794	0.085	NA	0.019
  AD-19057	136	795	0.599	NA	NA
  AD-19058	137	796	0.577	NA	NA
  AD-19059	138	797	0.728	NA	NA
  AD-19060	139	798	1.072	NA	NA
  AD-19061	140	799	0.885	NA	NA
  AD-19062	141	800	0.810	NA	NA
  AD-19063	142	801	0.741	NA	NA
  AD-19064	143	802	0.591	NA	NA
  AD-19065	144	803	0.323	NA	NA
  AD-19066	145	804	0.086	0.48	NA
  AD-19067	146	805	0.138	NA	NA
  AD-19068	147	806	0.321	NA	NA
  AD-19069	148	807	0.135	NA	1.403
  AD-19070	149	808	0.892	NA	NA
  AD-19071	150	809	0.658	NA	NA
  AD-19072	151	810	0.704	NA	NA
  AD-19073	152	811	0.838	NA	NA
  AD-19074	153	812	0.042	NA	0.008
  AD-19075	154	813	0.841	NA	NA
  AD-19076	155	814	0.037	NA	0.002
  AD-19077	156	815	0.226	NA	NA
  AD-19078	157	816	0.719	NA	NA
  AD-19079	158	817	0.545	NA	NA
  AD-19080	159	818	0.092	NA	0.172
  AD-19081	160	819	0.203	NA	8.936
  AD-19082	161	820	0.055	NA	0.090
  AD-19083	162	821	0.404	NA	NA
  AD-19738	163	822	1.361	NA	NA
  AD-19739	164	823	0.970	NA	NA
  AD-19740	165	824	0.679	NA	NA
  AD-19741	166	825	0.168	NA	NA
  AD-19742	167	826	0.958	NA	NA
  AD-19743	168	827	0.839	NA	NA
  AD-19744	169	828	0.978	NA	NA
  AD-19745	170	829	0.852	NA	NA
  AD-19746	171	830	0.086	NA	NA
  AD-19747	172	831	0.187	NA	NA
  AD-19748	173	832	0.794	NA	NA
  AD-19749	174	833	0.115	NA	NA
  AD-19750	175	834	0.317	NA	NA
  AD-19751	176	835	0.591	NA	NA
  AD-19752	177	836	0.089	NA	NA
  AD-19753	178	837	0.091	NA	NA
  AD-19754	179	838	0.756	NA	NA
  AD-19755	180	839	0.443	NA	NA
  AD-19756	181	840	0.529	NA	NA
  AD-19757	182	841	0.265	NA	NA
  AD-19758	183	842	0.139	NA	NA
  AD-19759	184	843	0.465	NA	NA
  AD-19760	185	844	0.213	NA	NA
  AD-19761	186	845	1.234	NA	NA
  AD-19762	187	846	0.085	NA	NA
  AD-19763	188	847	0.593	NA	NA
  AD-19765	189	848	0.031	NA	NA
  AD-19766	190	849	0.469	NA	NA
  AD-19767	191	850	0.587	NA	NA
  AD-19768	192	851	0.780	NA	NA
  AD-20124	193	852	0.123	0.44	NA
  AD-25889	194	853	0.605	0.73	NA
  AD-25890	195	854	0.034	0.49	NA
  AD-25891	196	855	0.041	0.16	0.050
  AD-25892	197	856	0.099	0.34	NA
  AD-25893	198	857	0.062	0.23	0.040
  AD-25894	199	858	0.033	0.13	0.004
  AD-25895	200	859	0.113	0.60	NA
  AD-25896	201	860	0.276	0.74	NA
  AD-25897	202	861	0.213	0.82	NA
  AD-25898	203	862	0.127	0.79	NA
  AD-25899	204	863	0.729	0.61	NA
  AD-25900	205	864	0.094	0.64	NA
  AD-25901	206	865	0.842	0.91	NA
  AD-25902	207	866	0.054	0.24	NA
  AD-25903	208	867	0.646	0.96	NA
  AD-25904	209	868	0.681	0.83	NA
  AD-25905	210	869	0.680	1.61	NA
  AD-25906	211	870	0.413	0.96	NA
  AD-25907	212	871	0.091	0.90	NA
  AD-25908	213	872	0.355	0.72	NA
  AD-25909	214	873	0.189	0.76	NA
  AD-25910	215	874	0.048	0.48	0.070
  AD-25911	216	875	0.134	0.81	NA
  AD-25912	217	876	0.095	0.66	NA
  AD-25913	218	877	0.291	0.94	NA
  AD-25914	219	878	0.057	0.47	0.054
  AD-25915	220	879	0.453	0.79	NA
  AD-25916	221	880	0.219	0.79	NA
  AD-25917	222	881	0.143	0.73	NA
  AD-25918	223	882	0.075	0.29	0.013
  AD-25919	224	883	0.123	0.68	NA
  AD-25920	225	884	0.255	0.69	NA
  AD-25921	226	885	0.637	0.81	NA
  AD-25922	227	886	0.283	0.83	NA
  AD-25923	228	887	0.575	0.64	NA
  AD-25924	229	888	0.118	0.52	NA
  AD-25925	230	889	0.242	0.96	NA
  AD-25926	231	890	0.150	0.67	NA
  AD-25927	232	891	0.394	0.72	NA
  AD-25928	233	892	0.138	0.62	NA
  AD-25929	234	893	0.073	0.50	NA
  AD-25930	235	894	0.095	0.71	NA
  AD-25931	236	895	0.076	0.77	NA
  AD-25932	237	896	0.073	0.61	NA
  AD-25933	238	897	0.113	0.79	NA
  AD-25934	239	898	0.223	0.46	NA
  AD-25935	240	899	0.288	0.78	NA
  AD-25936	241	900	0.413	0.78	NA
  AD-25937	242	901	0.838	0.77	NA
  AD-25938	243	902	0.038	0.08	0.006
  AD-25939	244	903	0.078	0.21	NA
  AD-25940	245	904	0.063	0.31	NA
  AD-25941	246	905	0.025	0.19	0.008
  AD-25942	247	906	0.029	0.20	0.016
  AD-25943	248	907	0.037	0.44	0.080
  AD-25944	249	908	0.038	0.23	0.007
  AD-25945	250	909	0.045	0.26	NA
  AD-25946	251	910	0.107	0.46	NA
  AD-25947	252	911	0.100	0.72	NA
  AD-25948	253	912	0.159	0.33	NA
  AD-25949	254	913	0.104	0.39	NA
  AD-25950	255	914	0.026	0.26	0.010
  AD-25951	256	915	0.026	0.28	0.007
  AD-25952	257	916	0.349	0.80	NA
  AD-25953	258	917	0.120	0.65	NA
  AD-25954	259	918	0.550	0.92	NA
  AD-25955	260	919	0.067	0.53	NA
  AD-25956	261	920	0.039	0.40	0.042
  AD-25957	262	921	0.105	0.64	NA
  AD-25958	263	922	0.044	0.38	0.024
  AD-25959	264	923	0.169	0.59	NA
  AD-25960	265	924	0.060	0.37	0.044
  AD-25961	266	925	0.162	0.67	NA
  AD-25962	267	926	0.684	0.76	NA
  AD-25963	268	927	0.106	0.48	0.275
  AD-25964	269	928	0.033	0.47	0.050
  AD-26017	270	929	0.113	0.87	NA
  AD-26018	271	930	0.060	0.37	NA
  AD-26019	272	931	0.106	0.42	NA
  AD-26020	273	932	0.043	0.50	NA
  AD-26021	274	933	0.046	0.69	NA
  AD-26022	275	934	0.109	0.83	NA
  AD-26023	276	935	0.637	0.80	NA
  AD-26024	277	936	0.226	0.73	NA
  AD-26025	278	937	0.252	0.96	NA
  AD-26026	279	938	0.088	0.58	NA
  AD-26027	280	939	0.228	0.96	NA
  AD-26028	281	940	0.025	0.28	0.050
  AD-26029	282	941	0.067	0.76	NA
  AD-26030	283	942	0.275	0.52	NA
  AD-26031	284	943	0.030	0.25	0.012
  AD-26032	285	944	0.078	0.50	NA
  AD-26033	286	945	0.353	0.69	NA
  AD-26034	287	946	0.022	0.16	0.009
  AD-26035	288	947	0.106	0.36	NA
  AD-26036	289	948	0.336	0.63	NA
  AD-26037	290	949	0.136	0.45	NA
  AD-26038	291	950	0.215	0.46	NA
  AD-26039	292	951	0.591	0.69	NA
  AD-26040	293	952	0.046	0.15	0.099
  AD-26041	294	953	0.324	0.67	NA
  AD-26042	295	954	0.026	0.38	0.010
  AD-26043	296	955	0.026	0.09	0.075
  AD-26044	297	956	0.034	0.37	NA
  AD-26045	298	957	0.531	0.77	NA
  AD-26046	299	958	0.531	0.58	NA
  AD-26047	300	959	0.023	0.47	0.058
  AD-26048	301	960	0.397	0.95	NA
  AD-26049	302	961	0.212	0.65	NA
  AD-26050	303	962	0.204	0.95	NA
  AD-26051	304	963	0.619	0.57	NA
  AD-26052	305	964	0.037	0.55	NA
  AD-26053	306	965	0.369	0.71	NA
  AD-26054	307	966	0.616	0.78	NA
  AD-26055	308	967	0.424	0.64	NA
  AD-26056	309	968	0.168	0.81	NA
  AD-26057	310	969	0.086	0.28	NA
  AD-26058	311	970	0.456	0.67	NA
  AD-26059	312	971	0.169	0.47	NA
  AD-26060	313	972	0.057	0.19	0.139
  AD-26061	314	973	0.050	0.42	NA
  AD-26062	315	974	0.110	0.64	NA
  AD-26063	316	975	0.021	0.74	NA
  AD-26064	317	976	0.785	0.62	NA
  AD-26065	318	977	0.678	0.84	NA
  AD-26066	319	978	0.035	0.44	NA
  AD-26067	320	979	0.305	0.51	NA
  AD-26068	321	980	0.028	0.50	0.102
  AD-26069	322	981	0.046	0.50	NA
  AD-26070	323	982	0.446	0.64	NA
  AD-26071	324	983	0.074	0.48	NA
  AD-26072	325	984	0.742	0.84	NA
  AD-26073	326	985	0.086	0.33	NA
  AD-26074	327	986	0.227	0.55	NA
  AD-26075	328	987	0.092	0.74	NA
  AD-26076	329	988	0.029	0.24	0.159
  AD-26077	330	989	0.191	0.70	NA
  AD-26078	331	990	0.032	0.32	0.106
  AD-26079	332	991	0.131	0.55	NA
  AD-26080	333	992	0.589	0.86	NA
  AD-26081	334	993	0.538	0.66	NA
  AD-26082	335	994	0.021	0.42	0.039
  AD-26083	336	995	0.049	0.25	NA
  AD-26084	337	996	0.334	0.75	NA
  AD-26085	338	997	0.192	0.69	NA
  AD-26086	339	998	0.524	0.62	NA
  AD-26087	340	999	0.276	0.71	NA
  AD-26088	341	1000	0.101	0.83	NA
  AD-26089	342	1001	0.821	0.93	NA
  AD-26090	343	1002	0.367	0.77	NA
  AD-26091	344	1003	0.022	0.32	0.057
  AD-26092	345	1004	0.246	0.75	NA
  AD-26093	346	1005	0.570	0.70	NA
  AD-26094	347	1006	0.145	0.57	NA
  AD-26095	348	1007	0.073	0.58	NA
  AD-26096	349	1008	0.109	0.51	NA
  AD-26097	350	1009	0.145	0.57	NA
  AD-26098	351	1010	0.101	0.43	NA
  AD-26099	352	1011	0.171	0.68	NA
  AD-26100	353	1012	0.058	0.21	NA
  AD-26101	354	1013	0.041	0.30	0.030
  AD-26102	355	1014	0.169	0.93	NA
  AD-26103	356	1015	0.209	0.61	NA
  AD-26104	357	1016	0.016	0.22	0.058
  AD-26105	358	1017	0.044	0.49	NA
  AD-26106	359	1018	0.169	0.75	NA
  AD-26107	360	1019	0.290	0.90	NA
  AD-26108	361	1020	0.040	0.50	0.030
  AD-26109	362	1021	0.024	0.22	0.025
  AD-26110	363	1022	0.326	0.79	NA
  AD-26111	364	1023	0.798	0.77	NA
  AD-26112	365	1024	0.301	0.51	NA
  AD-26123	366	1025	0.652	0.84	NA
  AD-26124	367	1026	0.277	0.48	NA
  AD-26125	368	1027	0.342	0.64	NA
  AD-26126	369	1028	0.094	0.46	NA
  AD-26127	370	1029	0.455	0.80	NA
  AD-26128	371	1030	0.058	0.24	0.066
  AD-26129	372	1031	0.409	0.57	NA
  AD-26130	373	1032	0.892	0.80	NA
  AD-26131	374	1033	0.067	0.41	0.104
  AD-26132	375	1034	0.109	0.19	0.060
  AD-26133	376	1035	0.790	0.85	NA
  AD-26134	377	1036	0.046	0.27	0.103
  AD-26135	378	1037	0.069	0.38	NA
  AD-26136	379	1038	0.451	0.78	NA
  AD-26137	380	1039	0.685	0.64	NA
  AD-26138	381	1040	0.579	0.63	NA
  AD-26139	382	1041	0.857	0.59	NA
  AD-26140	383	1042	0.384	0.71	NA
  AD-26141	384	1043	0.104	0.49	NA
  AD-26142	385	1044	0.199	0.59	NA
  AD-26143	386	1045	0.205	0.61	NA
  AD-26144	387	1046	0.821	1.04	NA
  AD-26145	388	1047	0.860	0.86	NA
  AD-26146	389	1048	0.076	0.34	NA
  AD-26147	390	1049	0.559	0.65	NA
  AD-26148	391	1050	0.066	0.48	NA
  AD-26149	392	1051	0.326	0.50	NA
  AD-26150	393	1052	0.396	0.66	NA
  AD-26151	394	1053	0.249	0.54	NA
  AD-26152	395	1054	0.837	0.74	NA
  AD-26153	396	1055	0.119	0.39	NA
  AD-26154	397	1056	0.600	0.64	NA
  AD-26155	398	1057	0.693	0.69	NA
  AD-26156	399	1058	0.033	0.35	0.020
  AD-26157	400	1059	0.220	0.74	NA
  AD-26158	401	1060	0.031	0.40	0.033
  AD-26159	402	1061	0.387	0.49	NA
  AD-26160	403	1062	0.836	0.73	NA
  AD-26161	404	1063	0.831	0.76	NA
  AD-26162	405	1064	0.358	0.50	NA
  AD-26163	406	1065	0.817	0.66	NA
  AD-26164	407	1066	0.112	0.59	NA
  AD-26165	408	1067	0.272	0.67	NA
  AD-26166	409	1068	0.300	0.63	NA
  AD-26167	410	1069	0.664	0.77	NA
  AD-26168	411	1070	0.771	0.78	NA
  AD-26169	412	1071	0.480	0.67	NA
  AD-26170	413	1072	0.174	0.47	NA
  AD-26171	414	1073	0.410	0.75	NA
  AD-26172	415	1074	0.294	0.74	NA
  AD-26173	416	1075	0.384	0.71	NA
  AD-26174	417	1076	0.388	0.79	NA
  AD-26175	418	1077	0.611	0.72	NA
  AD-26176	419	1078	0.055	0.44	NA
  AD-26177	420	1079	0.310	0.67	NA
  AD-26178	421	1080	0.038	0.20	0.094
  AD-26179	422	1081	0.042	0.33	0.108
  AD-26180	423	1082	0.031	0.21	0.036
  AD-26181	424	1083	0.041	0.08	0.034
  AD-26182	425	1084	0.237	0.79	NA
  AD-26183	426	1085	0.028	0.37	0.070
  AD-26184	427	1086	0.189	0.54	NA
  AD-26185	428	1087	0.357	0.76	NA
  AD-26186	6495	1088	0.066	0.60	NA
  AD-26187	6496	1089	0.298	0.60	NA
  AD-26188	431	1090	0.159	0.51	NA
  AD-26189	432	1091	0.143	0.51	NA
  AD-26190	433	1092	0.063	0.34	NA
  AD-26191	434	1093	0.674	0.82	NA
  AD-26192	435	1094	0.446	0.75	NA
  AD-26193	436	1095	0.058	0.36	0.055
  AD-26194	437	1096	0.289	0.84	NA
  AD-26195	438	1097	0.353	0.81	NA
  AD-26196	439	1098	0.055	0.35	NA
  AD-26197	440	1099	0.440	0.68	NA
  AD-26198	441	1100	0.175	0.53	NA
  AD-26199	442	1101	0.055	0.58	NA
  AD-26200	443	1102	0.076	0.46	NA
  AD-26201	444	1103	0.283	0.48	NA
  AD-26202	445	1104	0.052	0.70	NA
  AD-26203	446	1105	0.045	0.22	0.162
  AD-26204	447	1106	0.660	0.73	NA
  AD-26205	448	1107	0.324	0.76	NA
  AD-26206	449	1108	0.520	1.12	NA
  AD-26207	450	1109	0.367	0.75	NA
  AD-26208	451	1110	0.795	0.73	NA
  AD-26209	452	1111	0.112	0.54	NA
  AD-26210	453	1112	0.030	0.39	NA
  AD-26211	454	1113	0.124	0.25	NA
  AD-26212	455	1114	0.151	0.45	NA
  AD-26213	456	1115	0.223	0.63	NA
  AD-26214	457	1116	0.513	0.66	NA
  AD-26215	458	1117	0.102	0.29	NA
  AD-26216	459	1118	0.496	0.58	NA
  AD-26217	460	1119	0.410	0.77	NA
  AD-26218	461	1120	0.041	0.15	0.026
  AD-26651	462	1121	0.023	0.21	0.041
  AD-26652	463	1122	0.025	0.21	0.026
  AD-26653	464	1123	0.115	0.76	NA
  AD-26654	465	1124	0.068	0.88	NA
  AD-26655	466	1125	0.682	0.86	NA
  AD-26656	467	1126	0.684	0.91	NA
  AD-26657	468	1127	0.468	0.89	NA
  AD-26658	469	1128	0.305	0.50	NA
  AD-26659	470	1129	0.481	0.50	NA
  AD-26660	471	1130	0.041	0.20	0.010
  AD-26661	472	1131	0.194	0.77	NA
  AD-26662	473	1132	0.717	1.00	NA
  AD-26663	474	1133	0.546	1.02	NA
  AD-26664	475	1134	0.030	0.36	NA
  AD-26665	476	1135	0.037	0.25	0.008
  AD-26666	477	1136	0.072	0.57	NA
  AD-26667	478	1137	0.587	0.65	NA
  AD-26668	479	1138	0.760	0.70	NA
  AD-26669	480	1139	0.038	0.64	NA
  AD-26670	481	1140	0.033	0.32	0.005
  AD-26671	482	1141	0.091	0.71	NA
  AD-26672	483	1142	0.084	0.56	NA
  AD-26673	484	1143	0.027	0.18	0.012
  AD-26674	485	1144	0.044	0.32	0.021
  AD-26675	486	1145	0.063	0.67	NA
  AD-26676	487	1146	0.617	0.81	NA
  AD-26677	488	1147	0.138	0.50	NA
  AD-26678	489	1148	0.055	0.34	NA
  AD-26679	490	1149	0.052	0.44	NA
  AD-26680	491	1150	0.191	0.42	NA
  AD-26681	492	1151	0.092	0.57	NA
  AD-26682	493	1152	0.035	0.11	0.007
  AD-26683	494	1153	0.055	0.87	NA
  AD-26684	495	1154	0.035	0.16	0.009
  AD-26685	496	1155	0.034	0.37	NA
  AD-26686	497	1156	0.821	0.77	NA
  AD-26687	498	1157	0.151	0.29	NA
  AD-26688	499	1158	0.094	0.69	NA
  AD-26689	500	1159	0.086	0.61	NA
  AD-26690	501	1160	0.047	0.36	NA
  AD-26691	502	1161	0.030	0.24	0.020
  AD-26692	503	1162	0.222	0.62	NA
  AD-26693	504	1163	0.739	0.76	NA
  AD-26694	505	1164	0.331	0.63	NA
  AD-26695	506	1165	0.371	0.66	NA
  AD-26696	507	1166	0.023	0.37	0.027
  AD-26697	508	1167	1.024	0.80	NA
  AD-26698	509	1168	0.047	0.22	NA
  AD-26699	510	1169	0.145	0.71	NA
  AD-26700	511	1170	0.028	0.08	0.005
  AD-26701	512	1171	0.028	0.21	0.006
  AD-26702	513	1172	0.046	0.43	NA
  AD-26703	514	1173	0.193	0.65	NA
  AD-26704	515	1174	0.027	0.36	0.010
  AD-26705	516	1175	0.054	0.40	NA
  AD-26706	517	1176	0.223	0.52	NA
  AD-26707	518	1177	0.144	0.70	NA
  AD-26708	519	1178	0.160	0.59	NA
  AD-26709	520	1179	0.818	0.80	NA
  AD-26710	521	1180	0.307	0.84	NA
  AD-26711	522	1181	0.209	0.46	NA
  AD-26712	523	1182	0.276	0.76	NA
  AD-26713	524	1183	0.043	0.23	0.014
  AD-26714	525	1184	0.108	0.65	NA
  AD-26715	526	1185	0.777	0.67	NA
  AD-26716	527	1186	0.551	0.69	NA
  AD-26717	528	1187	0.643	0.80	NA
  AD-26718	529	1188	0.821	0.70	NA
  AD-26719	530	1189	0.053	0.35	NA
  AD-26720	531	1190	0.148	0.62	NA
  AD-26721	532	1191	0.906	0.92	NA
  AD-26722	533	1192	0.042	0.38	0.033
  AD-26723	534	1193	0.136	0.69	NA
  AD-26724	535	1194	0.472	1.00	NA
  AD-26725	536	1195	0.082	0.39	NA
  AD-26726	537	1196	0.258	0.70	NA
  AD-26727	538	1197	0.043	0.33	NA
  AD-26728	539	1198	0.612	0.80	NA
  AD-26729	540	1199	0.056	0.15	0.007
  AD-26730	541	1200	0.038	0.13	0.007
  AD-26731	542	1201	0.034	0.10	0.035
  AD-26732	543	1202	0.853	0.74	NA
  AD-26733	544	1203	0.805	0.77	NA
  AD-26734	545	1204	0.580	0.77	NA
  AD-26735	546	1205	0.457	1.02	NA
  AD-26736	547	1206	0.701	0.75	NA
  AD-26737	548	1207	0.066	0.33	NA
  AD-26738	549	1208	0.327	0.79	NA
  AD-26739	550	1209	0.102	0.44	NA
  AD-26740	551	1210	0.030	0.08	0.006
  AD-26741	552	1211	0.128	0.50	NA
  AD-26742	553	1212	0.025	0.34	0.057
  AD-26743	554	1213	0.033	0.38	0.061
  AD-26744	555	1214	0.170	0.74	NA
  AD-26745	556	1215	0.304	0.55	NA
  AD-26746	557	1216	0.037	0.33	NA
  AD-26747	558	1217	0.048	0.43	NA
  AD-26748	559	1218	0.081	0.51	NA
  AD-26749	560	1219	0.184	0.70	NA
  AD-26750	561	1220	0.209	0.64	NA
  AD-26751	562	1221	0.570	0.71	NA
  AD-26752	563	1222	0.040	0.45	0.042
  AD-26753	564	1223	0.153	0.61	NA
  AD-26754	565	1224	0.518	0.79	NA
  AD-26755	566	1225	0.064	0.27	NA
  AD-26756	567	1226	0.146	0.48	NA
  AD-26757	568	1227	0.035	0.22	0.047
  AD-26758	569	1228	0.053	0.46	NA
  AD-26759	570	1229	0.116	0.59	NA
  AD-26760	571	1230	0.435	0.60	NA
  AD-26761	572	1231	0.088	0.44	NA
  AD-26762	573	1232	0.385	0.57	NA
  AD-26763	574	1233	0.057	0.22	0.015
  AD-26764	575	1234	0.120	0.47	NA
  AD-26765	576	1235	0.058	0.43	NA
  AD-26766	577	1236	0.183	0.72	NA
  AD-26767	578	1237	0.582	0.57	NA
  AD-26768	579	1238	0.042	0.39	NA
  AD-26769	580	1239	0.071	0.52	NA
  AD-26770	581	1240	0.398	0.58	NA
  AD-26771	582	1241	0.576	0.71	NA
  AD-26772	583	1242	0.784	0.64	NA
  AD-26773	584	1243	0.353	0.58	NA
  AD-26774	585	1244	0.069	0.55	NA
  AD-26775	586	1245	0.506	0.86	NA
  AD-26776	587	1246	0.079	0.26	NA
  AD-26777	588	1247	0.363	0.73	NA
  AD-26778	589	1248	0.101	0.40	NA
  AD-26779	590	1249	0.040	0.34	0.109
  AD-26780	591	1250	0.069	0.25	NA
  AD-26781	592	1251	0.044	0.24	NA
  AD-26782	593	1252	0.054	0.53	NA
  AD-26783	594	1253	0.053	0.51	NA
  AD-26784	595	1254	0.072	0.53	NA
  AD-26785	596	1255	0.201	0.51	NA
  AD-26786	597	1256	0.134	0.81	NA
  AD-26787	598	1257	0.143	0.60	NA
  AD-26788	599	1258	0.036	0.57	0.053
  AD-26789	600	1259	0.418	0.74	NA
  AD-26790	601	1260	0.122	0.62	NA
  AD-26791	602	1261	0.305	0.73	NA
  AD-26792	603	1262	0.346	0.76	NA
  AD-26793	604	1263	0.391	0.63	NA
  AD-26794	605	1264	0.077	0.40	NA
  AD-26795	606	1265	0.586	0.65	NA
  AD-26796	607	1266	0.392	0.70	NA
  AD-26797	608	1267	0.063	0.73	NA
  AD-26798	609	1268	0.249	0.62	NA
  AD-26799	610	1269	0.345	0.66	NA
  AD-26800	611	1270	0.034	0.20	0.025
  AD-26801	612	1271	0.044	0.46	NA
  AD-26802	613	1272	0.096	0.57	NA
  AD-26803	614	1273	0.162	0.57	NA
  AD-26804	615	1274	0.056	0.35	NA
  AD-26805	616	1275	0.742	0.66	NA
  AD-26806	617	1276	0.080	0.69	NA
  AD-26807	618	1277	0.517	0.62	NA
  AD-26808	619	1278	0.043	0.51	NA
  AD-26809	620	1279	0.227	0.61	NA
  AD-26810	621	1280	0.048	0.22	0.039
  AD-26811	622	1281	0.333	0.85	NA
  AD-26812	623	1282	0.522	0.84	NA
  AD-26813	624	1283	0.044	0.33	0.076
  AD-26814	625	1284	0.545	0.72	NA
  AD-26815	626	1285	0.594	0.63	NA
  AD-26816	627	1286	0.044	0.37	NA
  AD-26817	628	1287	0.523	0.68	NA
  AD-26818	629	1288	0.575	1.80	NA
  AD-26819	630	1289	0.069	0.41	NA
  AD-26820	631	1290	0.484	0.76	NA
  AD-26821	632	1291	0.245	0.70	NA
  AD-26822	633	1292	0.039	0.23	0.037
  AD-26823	634	1293	0.062	0.09	0.033
  AD-26824	635	1294	0.304	0.60	NA
  AD-26825	636	1295	0.038	0.36	NA
  AD-26826	637	1296	0.105	0.57	NA
  AD-26900	638	1297	0.056	0.73	0.033
  AD-26901	639	1298	0.065	0.68	NA
  AD-26902	640	1299	0.053	0.42	NA
  AD-26903	641	1300	0.075	0.59	NA
  AD-26904	642	1301	0.051	0.38	NA
  AD-26905	643	1302	0.084	0.45	NA
  AD-26906	644	1303	0.186	0.76	NA
  AD-26907	645	1304	0.610	0.82	NA
  AD-26908	646	1305	0.073	0.78	NA
  AD-26909	647	1306	0.235	0.99	NA
  AD-26910	648	1307	0.077	0.78	NA
  AD-26911	649	1308	0.193	0.96	NA
  AD-26912	650	1309	0.074	0.73	NA
  AD-26913	651	1310	0.141	0.88	NA
  AD-26914	652	1311	0.519	0.64	NA
  AD-26915	653	1312	0.587	0.71	NA
  AD-26916	654	1313	0.063	0.62	NA
  AD-26917	655	1314	0.076	0.55	NA
  AD-26918	656	1315	0.069	0.28	0.029
  AD-26919	657	1316	0.085	0.55	NA
  AD-26920	658	1317	0.042	0.31	NA
  AD-26921	659	1318	0.025	0.09	0.014

• NA: data not available or not determined.
• “Fold-Change” represents the residual level (in HeLa cells) at a particular time and concentration, relative to control. Thus, a “Fold-Change 10 nM 24 hr” for AD-18892 of “0.054” indicates that, at a concentration of 10 nM, there was 5.4% residual Beta-Catenin level, or 94.6% gene knock-down, in HeLa cells at 24 hr after treating the cells with the RNAi agent.
• “Fold-Change 0.1 nM 120 hr” indicates the residual Beta-Catenin level at a concentration of 0.1 nM, measured at 120 hr.
• “Avg. EC50 (nM)” indicates a concentration estimated, based on available data, to allow 50% gene knock-down in HeLa cells. Thus, for AD-18893, a concentration of 0.008 nM is estimated to knock down Beta-Catenin by 50%. To calculate estimated average EC50 figures, HeLa cells were treated with RNAi agents at concentrations of 10 nM, 1 nM, 0.1 nM, 0.01 nM, and 0.001 nM of RNAi agent, and the data fit to a curve. The indicated EC50 is an estimated EC50 calculated from available data that is expected to give 50% gene knock-down of Beta-Catenin in HeLa cells.
• Tables 1 to 8 thus disclose various RNAi agents capable of mediating gene knock-down of Beta-Catenin.

• TABLE 6
  Analysis of RNAi agents to Beta-Catenin

  	AV HeLa	AV HeLa	AV HeLa	SD HeLa	SD HeLa	SD HeLa
  	set1-2	set1-2	set1-2	set1-2	set1-2	set1-2
  Nickname	d3-6 nM	3 nM	1.5 nM	d3-6 nM	3 nM	1.5 nM

  Set1 254 A22 S26	4.9	11.1	22.5	1.6	2.1	1.6
  Set1 703 A22 S26	4.8	12.4	29.0	1.5	2.4	7.3
  Set1 709 A22 S26	6.5	13.9	30.7	1.1	2.0	7.1
  Set1 895 A22 S26	5.9	13.1	48.0	0.8	3.9	25.6
  Set1 1816 A22 S26	4.9	12.3	28.6	0.5	2.8	4.3
  Set1 1974 A22 S26	6.6	12.5	36.9	1.0	0.9	0.6
  Set1 2425 A22 S26	5.6	13.6	27.3	0.4	1.7	9.7
  Set1 3146 A22 S26	4.5	9.3	21.0	1.1	1.2	2.9
  Set1 889 A22 S26	8.6	14.2	37.9	3.4	3.7	17.1
  Set1 1814 A22 S26	6.0	11.8	21.3	2.2	3.8	4.6
  Set1 1245 A22 S26	6.7	12.0	28.2	2.6	2.5	8.7
  Set1 3196 A22 S26	4.5	9.1	17.1	0.5	0.0	5.3
  Set1 1450 A22 S26	4.4	12.5	25.4	0.3	3.6	2.7
  Set1 3169 A22 S26	6.3	13.1	29.7	0.9	2.2	9.8
  Set1 3477 A22 S26	9.6	19.8	40.9	2.0	2.6	10.9
  Set1 865 A22 S26	12.0	24.5	57.3	3.3	7.5	14.2
  Set1 1249 A22 S26	34.4	71.2	73.3	7.9	24.7	12.3
  Set1 1250 A22 S26	12.0	30.6	61.6	2.0	8.4	4.2
  Set1 2202 A22 S26	8.3	14.0	45.8	3.1	1.8	12.2
  Set1 1545 A22 S26	34.4	62.0	81.5	11.6	4.1	12.5
  Set1 1755 A22 S26	8.7	21.9	64.9	1.0	6.4	8.0
  Set1 254 A25 S27	6.3	12.3	17.6	1.2	3.4	1.7
  Set1 703 A25 S27	7.0	13.7	32.8	1.2	2.9	8.0
  Set1 709 A25 S27	5.6	11.4	23.4	1.8	0.5	7.7
  Set1 895 A25 S27	6.6	13.5	35.7	1.9	2.5	6.8
  Set1 1816 A25 S27	7.8	15.6	26.4	1.3	1.2	4.8
  Set1 1974 A25 S27	8.1	16.2	34.7	2.6	1.3	3.8
  Set1 2425 A25 S27	7.8	16.5	35.3	1.0	2.2	2.5
  Set1 3146 A25 S27	4.9	11.9	31.0	0.3	1.3	4.2
  Set1 889 A25 S27	9.3	15.0	37.2	1.3	1.9	4.1
  Set1 1814 A25 S27	6.2	13.7	43.2	1.1	0.9	6.1
  Set1 1245 A25 S27	7.2	15.2	36.2	0.3	2.4	11.7
  Set1 3196 A25 S27	5.5	10.3	24.2	1.4	0.8	2.1
  Set1 1450 A25 S27	4.3	10.4	29.9	1.1	1.1	6.4
  Set1 3169 A25 S27	4.3	11.5	22.0	0.4	2.3	2.7
  Set1 3477 A25 S27	7.5	12.8	22.8	1.1	1.3	2.1
  Set1 865 A25 S27	5.1	10.9	18.1	0.7	1.2	2.9
  Set1 1249 A25 S27	8.0	22.9	37.2	1.8	5.1	6.7
  Set1 1250 A25 S27	16.6	28.2	49.1	3.1	2.7	8.9
  Set1 2202 A25 S27	6.1	10.0	29.2	2.3	3.6	4.8
  Set1 1545 A25 S27	9.0	16.6	41.9	1.3	2.2	2.2
  Set1 1755 A25 S27	5.8	15.1	33.8	1.2	2.2	6.1
  Set1 254 A LO V1 S26	6.0	16.4	32.9	0.3	3.8	5.1
  Set1 703 A LO V1 S26	8.1	22.7	50.3	2.8	3.4	16.2
  Set1 709 A LO V1 S26	6.2	14.8	37.1	1.2	1.7	5.1
  Set1 895 A LO V1 S26	42.7	63.9	82.3	7.8	15.5	10.2
  Set1 1816 A LO V1 S26	6.9	16.9	43.4	0.9	1.4	15.1
  Set1 1974 A LO V1 S26	9.0	18.5	36.8	1.4	3.6	6.8
  Set1 2425 A LO V1 S26	5.5	13.9	30.0	0.4	1.6	7.5
  Set1 3146 A LO V1 S26	12.1	27.7	61.2	1.5	2.7	3.8
  Set1 889 A LO V1 S26	24.5	37.8	60.3	3.2	3.2	9.1
  Set1 1814 A LO V1 S26	8.6	20.7	46.5	1.5	2.6	11.1
  Set1 1245 A LO V1 S26	42.0	61.4	85.9	5.8	8.4	10.4
  Set1 3196 A LO V1 S26	6.1	14.0	31.0	0.6	1.2	5.4
  Set1 1450 A LO V1 S26	9.4	21.1	47.6	1.4	1.3	8.0
  Set1 3169 A LO V1 S26	5.3	15.5	30.5	1.3	3.7	1.9
  Set1 3477 A LO V1 S26	8.6	16.9	39.8	1.0	1.0	2.3
  Set1 865 A LO V1 S26	5.5	18.1	34.5	0.9	3.1	11.0
  Set1 1249 A LO V1 S26	61.0	90.3	82.0	5.6	29.0	6.6
  Set1 1250 A LO V1 S26	11.3	23.1	58.2	0.9	3.0	5.1
  Set1 2202 A LO V1 S26	5.7	14.5	45.2	1.0	1.4	1.5
  Set1 1545 A LO V1 S26	5.6	13.1	38.6	0.4	0.9	3.2
  Set1 1755 A LO V1 S26	39.5	53.6	77.5	3.8	3.3	5.0
  Set1 254 A LO V2 S LO V1	8.7	18.6	44.9	2.5	1.4	6.6
  Set1 703 A LO V2 S LO V1	39.9	51.7	75.8	3.9	3.2	9.9
  Set1 709 A LO V2 S LO V1	9.2	20.3	45.0	1.2	0.7	8.7
  Set1 895 A LO V2 S LO V1	33.3	64.9	84.8	1.8	6.5	5.8
  Set1 1816 A LO V2 S LO V1	14.4	33.1	61.2	2.2	2.9	9.3
  Set1 1974 A LO V2 S LO V1	56.7	65.4	91.8	15.4	5.6	6.7
  Set1 2425 A LO V2 S LO V1	13.3	21.4	54.2	1.5	3.6	6.0
  Set1 3146 A LO V2 S LO V1	9.7	16.7	32.7	2.0	1.7	5.0
  Set1 889 A LO V2 S LO V1	18.0	34.6	58.8	1.4	4.2	7.0
  Set1 1814 A LO V2 S LO V1	8.9	18.5	44.1	3.3	5.0	1.0
  Set1 1245 A LO V2 S LO V1	52.2	43.1	93.4	13.1	4.1	6.2
  Set1 3196 A LO V2 S LO V1	7.8	15.1	28.0	2.7	3.1	2.5
  Set1 1450 A LO V2 S LO V1	6.6	14.4	35.0	0.4	2.0	4.0
  Set1 3169 A LO V2 S LO V1	5.3	14.5	26.4	0.5	2.8	2.2
  Set1 3477 A LO V2 S LO V1	9.4	22.0	35.2	1.5	0.8	1.6
  Set1 865 A LO V2 S LO V1	11.2	18.5	45.9	5.4	4.2	18.2
  Set1 1249 A LO V2 S LO V1	65.5	97.0	82.0	19.2	22.0	10.3
  Set1 1250 A LO V2 S LO V1	49.4	62.9	92.4	6.3	19.6	22.4
  Set1 2202 A LO V2 S LO V1	6.7	17.3	34.9	0.8	3.6	1.6
  Set1 1545 A LO V2 S LO V1	17.9	32.6	58.3	1.2	5.0	8.2
  Set1 1755 A LO V2 S LO V1	10.5	23.3	43.1	1.0	3.3	7.3
  Set2 254 A LO V3 S LO V2	15.0	88.6	75.0	3.4	21.7	4.4
  Set2 703 A LO V3 S LO V2	112.0	235.3	135.2	25.2	30.1	22.4
  Set2 709 A LO V3 S LO V2	36.7	93.6	98.4	2.6	7.6	4.8
  Set2 895 A LO V3 S LO V2	80.2	163.3	117.7	9.1	62.4	10.6
  Set2 1816 A LO V3 S LO V2	66.3	113.1	116.6	10.0	22.2	12.6
  Set2 1974 A LO V3 S LO V2	110.7	142.7	134.5	13.1	19.0	12.8
  Set2 2425 A LO V3 S LO V2	50.9	119.3	151.5	13.1	20.2	7.0
  Set2 3146 A LO V3 S LO V2	30.8	73.2	99.6	5.0	13.5	14.3
  Set2 889 A LO V3 S LO V2	72.5	135.6	112.8	12.0	37.8	9.4
  Set2 1814 A LO V3 S LO V2	80.7	129.6	133.9	23.6	13.9	15.2
  Set2 1245 A LO V3 S LO V2	94.9	128.9	129.1	13.2	18.1	13.8
  Set2 3196 A LO V3 S LO V2	20.5	69.2	89.8	1.4	8.7	15.8
  Set2 1450 A LO V3 S LO V2	35.3	95.3	109.0	1.6	15.1	16.1
  Set2 3169 A LO V3 S LO V2	26.2	90.9	85.7	8.9	26.1	7.7
  Set2 3477 A LO V3 S LO V2	16.3	71.8	68.0	3.7	20.3	2.2
  Set2 865 A LO V3 S LO V2	99.3	122.9	115.4	9.0	29.0	14.5
  Set2 1249 A LO V3 S LO V2	62.7	114.9	113.5	7.5	19.6	3.4
  Set2 1250 A LO V3 S LO V2	101.9	112.5	116.1	8.7	12.1	11.1
  Set2 2202 A LO V3 S LO V2	72.2	118.5	129.7	7.1	22.3	7.5
  Set2 1545 A LO V3 S LO V2	65.6	109.5	120.7	12.9	6.5	9.3
  Set2 1755 A LO V3 S LO V2	84.7	140.6	146.9	11.1	52.2	13.5
  Set2 254 A LO V4 S LO V1	11.2	50.5	59.8	1.4	4.6	4.5
  Set2 703 A LO V4 S LO V1	29.1	94.0	100.5	3.4	10.3	6.1
  Set2 709 A LO V4 S LO V1	6.3	25.9	32.9	0.2	2.6	2.2
  Set2 895 A LO V4 S LO V1	26.4	86.4	108.5	1.2	6.5	30.8
  Set2 1816 A LO V4 S LO V1	15.0	94.1	88.1	1.5	13.2	25.2
  Set2 1974 A LO V4 S LO V1	47.3	100.2	126.0	9.1	4.5	21.6
  Set2 2425 A LO V4 S LO V1	13.0	44.3	61.8	3.7	1.7	6.9
  Set2 3146 A LO V4 S LO V1	11.8	36.2	34.8	2.5	2.4	3.6
  Set2 889 A LO V4 S LO V1	28.9	79.6	79.8	9.2	13.4	10.7
  Set2 1814 A LO V4 S LO V1	10.4	50.1	62.9	0.9	17.3	9.2
  Set2 1245 A LO V4 S LO V1	31.7	88.0	105.1	5.3	18.8	14.2
  Set2 3196 A LO V4 S LO V1	9.8	27.2	39.2	1.1	1.4	4.9
  Set2 1450 A LO V4 S LO V1	8.9	27.8	44.0	2.1	7.6	10.9
  Set2 3169 A LO V4 S LO V1	8.1	26.3	29.7	1.4	7.1	6.6
  Set2 3477 A LO V4 S LO V1	7.9	19.2	29.1	0.6	2.5	9.5
  Set2 865 A LO V4 S LO V1	6.2	23.8	33.4	0.6	0.7	5.6
  Set2 1249 A LO V4 S LO V1	69.5	103.4	103.4	19.1	17.3	11.8
  Set2 1250 A LO V4 S LO V1	61.4	90.3	94.6	15.3	12.4	11.7
  Set2 2202 A LO V4 S LO V1	9.3	35.7	42.8	2.9	6.9	5.5
  Set2 1545 A LO V4 S LO V1	32.8	68.0	92.2	6.1	17.1	23.2
  Set2 1755 A LO V4 S LO V1	13.9	50.4	62.0	3.6	4.6	12.5
  Set2 254 A LO V5 S LO V1	11.4	28.3	52.5	1.8	8.2	4.8
  Set2 703 A LO V5 S LO V1	31.1	88.4	97.0	1.4	14.7	6.3
  Set2 709 A LO V5 S LO V1	13.0	34.2	37.9	3.4	8.8	5.7
  Set2 895 A LO V5 S LO V1	25.9	81.1	109.1	3.0	8.2	20.0
  Set2 1816 A LO V5 S LO V1	12.9	42.3	53.7	2.5	7.0	12.1
  Set2 1974 A LO V5 S LO V1	39.5	80.3	93.6	11.6	5.5	10.4
  Set2 2425 A LO V5 S LO V1	11.5	38.8	59.9	1.4	5.4	3.3
  Set2 3146 A LO V5 S LO V1	9.3	32.1	41.6	0.7	5.6	4.3
  Set2 889 A LO V5 S LO V1	26.9	64.9	89.5	5.2	23.5	17.5
  Set2 1814 A LO V5 S LO V1	11.0	47.9	79.5	1.5	9.1	11.6
  Set2 1245 A LO V5 S LO V1	29.5	78.6	127.3	2.2	5.1	16.7
  Set2 3196 A LO V5 S LO V1	8.1	28.6	55.6	0.7	9.8	9.7
  Set2 1450 A LO V5 S LO V1	6.6	27.8	46.3	1.6	12.7	12.4
  Set2 3169 A LO V5 S LO V1	7.8	24.2	32.6	1.5	0.8	5.5
  Set2 3477 A LO V5 S LO V1	11.5	46.6	57.9	2.3	25.4	7.1
  Set2 865 A LO V5 S LO V1	11.4	35.2	40.9	1.6	8.6	6.7
  Set2 1249 A LO V5 S LO V1	52.0	82.3	89.6	3.2	3.0	12.9
  Set2 1250 A LO V5 S LO V1	45.0	75.2	97.3	6.1	4.2	13.0
  Set2 2202 A LO V5 S LO V1	5.8	26.1	35.7	0.8	5.2	4.2
  Set2 1545 A LO V5 S LO V1	23.8	59.7	73.5	3.5	18.3	11.0
  Set2 1755 A LO V5 S LO V1	10.8	40.5	73.9	0.8	10.6	4.8
  Set2 254 A48 S26	7.3	20.0	36.8	0.8	1.5	1.7
  Set2 703 A48 S26	7.4	27.7	48.1	0.7	2.6	5.7
  Set2 709 A48 S26	10.3	35.4	42.0	0.3	12.1	1.3
  Set2 895 A48 S26	8.7	30.7	64.5	0.7	6.6	8.0
  Set2 1816 A48 S26	10.0	29.4	36.0	1.8	6.7	7.5
  Set2 1974 A48 S26	9.3	27.7	45.1	1.3	7.5	2.3
  Set2 2425 A48 S26	8.2	38.6	40.5	1.8	2.5	6.6
  Set2 3146 A48 S26	5.8	22.4	28.5	0.5	2.2	5.6
  Set2 889 A48 S26	7.2	21.9	30.6	0.9	5.9	2.8
  Set2 1814 A48 S26	7.3	19.3	25.2	2.6	7.8	7.6
  Set2 1245 A48 S26	8.3	47.7	58.2	2.0	19.3	10.5
  Set2 3196 A48 S26	8.0	20.2	27.0	0.4	6.9	7.2
  Set2 1450 A48 S26	7.5	27.4	40.4	1.8	9.7	6.6
  Set2 3169 A48 S26	8.4	18.2	30.5	0.8	3.1	7.4
  Set2 3477 A48 S26	12.5	44.1	59.8	2.2	10.3	5.5
  Set2 865 A48 S26	13.0	38.2	42.5	2.4	5.3	8.4
  Set2 1249 A48 S26	47.7	74.5	88.6	9.0	13.3	12.3
  Set2 1250 A48 S26	11.5	56.4	66.0	2.4	7.2	7.4
  Set2 2202 A48 S26	6.7	28.1	33.2	0.8	5.4	4.9
  Set2 1545 A48 S26	37.0	72.7	61.7	10.9	13.6	24.3
  Set2 1755 A48 S26	8.4	25.9	39.7	2.4	4.7	6.4
  Additional duplexes targeting Beta-Catenin (listed in Table 3) were tested in vitro against HeLa cells. 48 hour results were measured; duplex concentration was 6 nM, 3 nM and 1.5 nM. Data in this table represents residual gene activity; thus Set1 254 A22 S26 showed 4.9% residual gene activity (e.g., 95.1% gene knockdown) at 48 hours at 6 nM in HeLa cells.

Example 4
• Screening in Insensitive Cells
• In various embodiments, preferred RNAi agents to Beta-Catenin are those which are specific to Beta-Catenin and, in effect, do not exhibit off-target effects. Thus, in order to continue lead selection, various RNAi agents to Beta-Catenin are tested against cell lines which produce little or no Beta-Catenin. The Beta-Catenin RNAi agents which do not greatly reduce viability of these so-called “insensitive cell lines” are thought to have little or not off-target effects. The “insensitive” cell lines used are NCI-H28 and RKO. NCI-H28 is a mesothelioma cell line in which the Beta-Catenin gene has been deleted; RKO is a colorectal cell line which has low or no Beta-Catenin expression.
• 105 RNAi agents to Beta-Catenin found had been found to be effective in the dose-response analysis. These are tested against “insensitive” cell lines used are NCI-H28 and RKO at doses of 50 nM, 10 nM, 1 nM, 0.1 nM, and 0.0001 nM, and cell viability is determined at the time points of 3, 5 and 7 days.
• The following RNAi agents demonstrate at least 80% viability (no more than 20% growth inhibition) of RKO cells and at least 80% viability of NCI-H28 cells on day 5, at 50 or 10 nM.

• 	TABLE 7
  	RNAi agent	IC50
  	AD-18963-b2	0.049
  	AD-25894-b1	0.004
  	AD-25914-b1	0.054
  	AD-25956-b1	0.042
  	AD-26028-b1	0.050
  	AD-26034-b1	0.009
  	AD-26108-b1	0.030
  	AD-26131-b1	0.104
  	AD-26134-b1	0.103
  	AD-26158-b1	0.033
  	AD-26193-b1	0.055
  	AD-26218-b1	0.026
  	AD-26652-b1	0.026
  	AD-26704-b1	0.010
  	AD-26900-b1	0.033
  	AD-26918-b1	0.029

• The following RNAi agents demonstrate at least 80% viability (no more than 20% growth inhibition) of RKO cells and about 60 to 80% viability of NCI-H28 cells on day 5, at 50 or 10 nM.

• 	TABLE 8
  	RNAi Agent	IC50
  	AD-18983-b2	0.070
  	AD-25893-b1	0.040
  	AD-25918-b1	0.013
  	AD-25943-b1	0.080
  	AD-25944-b1	0.007
  	AD-25951-b1	0.007
  	AD-25958-b1	0.024
  	AD-26068-b1	0.102
  	AD-26109-b1	0.025
  	AD-26156-b1	0.020
  	AD-26673-b1	0.012
  	AD-26682-b1	0.007
  	AD-26696-b1	0.027
  	AD-26740-b1	0.006
  	AD-26752-b1	0.042
  	AD-26757-b1	0.047
  	AD-26779-b1	0.109
  	AD-26788-b1	0.053
  	AD-26800-b1	0.025

• Thus, 35 RNAi agents to Beta-Catenin did not greatly reduce viability of cell lines which do not depend on Beta-Catenin; these 35 RNAi agents to Beta-Catenin are: AD-18963-b2, AD-18983-b2, AD-25893-b1, AD-25894-b1, AD-25914-b1, AD-25918-b1, AD-25943-b1, AD-25944-b1, AD-25951-b1, AD-25956-b1, AD-25958-b1, AD-26028-b1, AD-26034-b1, AD-26068-b1, AD-26108-b1, AD-26109-b1, AD-26131-b1, AD-26134-b1, AD-26156-b1, AD-26158-b1, AD-26193-b1, AD-26218-b1, AD-26652-b1, AD-26673-b1, AD-26682-b1, AD-26696-b1, AD-26704-b1, AD-26740-b1, AD-26752-b1, AD-26757-b1, AD-26779-b1, AD-26788-b1, AD-26800-b1, AD-26900-b1, and AD-26918-b1 (wherein “b1” indicates “batch 1”).
Example 5
• Screening in Sensitive Cell Lines
• Further screening is performed on the 35 RNAi agents to Beta-Catenin which were able to reduce Beta-Catenin expression in vitro, and did which did not greatly reduce viability of cell lines which do not depend on Beta-Catenin, as shown in the previous Examples.
• These 35 RNAi agents were tested on four colorectal cell lines with an APC mutation (LoVo, DLD-1, LS411N and SW403). In the wild-type Wnt pathway, Beta-Catenin protein is phosphorylated by GSK-3, and then degraded by APC; thus, Beta-Catenin protein levels do not accumulate. However, in the case of the APC mutation, the Beta-Catenin is not degraded and thus the protein accumulates. These four cell lines are, in fact, dependent on Beta-Catenin and stop growing if Beta-Catenin expression is down-regulated.
• The cell lines are each treated with each of the 35 RNAi agents to Beta-Catenin at doses of 50 nM, 10 nM, 1 nM, 0.1 nM, and 0.0001 nM, and tested at 3, 5 and 7 days. The data used are from DLD-1 treated at 1 nM, LoVo at 1 nM, and LS411N at 0.1 nM, and data collected at 7 days. SW403 data is not used, as these data did not distinguish among the various siRNAs even at 0.1 nM.
• The screening data for RNAi agents to Beta-Catenin in sensitive cell lines is presented below.

• TABLE 9
  SCREENING DATA

  			24 hr	DLD1	LoVo	LS411N
  			Average	1 nM	1 nM	0.1 nM
  siRNA	Pos	Species	IC50 (nM)	Day 7	Day 7	Day 7	PBMC

  AD-18983	CDS	Hu, Cy, Mo	0.07	0.258	0.150	0.054	Neg
  AD-26156	CDS	Hu, Cy, Mo	0.02	0.458	0.194	0.187	Neg
  AD-25951	3′ UTR	Hu, Cy	0.007	0.659	0.188	0.465	Neg
  AD-26109	CDS	Hu, Cy	0.025	0.156	0.172	0.410	Neg
  AD-26218	CDS	Hu, Cy	0.026	0.376	0.243	0.566	Neg
  AD-25894	3′ UTR	Hu, Cy	0.004	0.378	0.293	0.307	Neg
  AD-26740	CDS	Hu, Cy	0.006	0.511	0.227	0.330	Neg
  AD-26158	CDS	Hu, Cy	0.033	0.347	0.227	0.398	Neg
  AD-26682	CDS	Hu, Cy	0.007	0.484	0.297	0.923	Neg
  AD-26034	CDS	Hu, Cy	0.009	0.673	0.267	0.656	Neg
  AD-25944	3′ UTR	Hu, Cy	0.007	0.633	0.264	0.589	Neg
  AD-26800	CDS	Hu, Cy	0.025	0.449	0.240	0.815	Neg
  AD-26108	CDS	Hu, Cy	0.03	0.437	0.305	0.880	Neg
  AD-26752	CDS	Hu, Cy	0.042	0.518	0.396	0.500	Neg
  AD-26918	3′ UTR	Hu, Cy	0.029	0.371	0.345	0.965	Neg

• In this table, the position is shown, wherein CDS indicates the coding segment (or open reading frame), and 3 ‘UTR indicates the 3’ untranslated region. The species forms of Beta-Catenin to which the RNAi agents match is also shown. Thus, AD-18983 matches each of the hman (Hu), cynomolgus (Cy), and Mouse (Mo) forms of Beta-Catenin. The estimated 24-hr average IC50 is shown (in nM). The cell viability in DLD1, LoVo, and LS411N cells is shown. For AD-18983, “0.258” indicates that at 1 nM at day 7, there was 25.8% cell viability of DLD1 cells, or 74.2% viability reduction. Similarly, there was 15.0% cell viability of LoVo cells (85.5% viability reduction) at 1 nM, and 5.4% cell viability (94.6% viability reduction) of LS411N cells (at 0.1 nM). PBMC indicates the peripheral blood mononuclear cell assay used as a test to measure potential immunogenicity of RNAi agents; “Neg” indicates that the RNAi agents did not illicit an immune response, as indicated by an increase in INF-α and TNF-α.
• Thus, the following RNAi agents to Beta-Catenin demonstrated a significant reduction of cell viability in at least one colorectal cell line that depends on Beta-Catenin for growth: AD-18963-b2, AD-25894-b1, AD-25944-b1, AD-25951-b1, AD-26034-b1, AD-26108-b1, AD-26109-b1, AD-26156-b1, AD-26158-b1, AD-26218-b1, AD-26682-b1, AD-26740-b1, AD-26752-b1, AD-26800-b1, and AD-26918-b1.
EQUIVALENTS
• A composition of embodiment 1 is a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-Catenin provided in Table 1.
• The composition of embodiment 1, wherein the composition further comprises a second RNAi agent to Beta-Catenin.
• The composition of embodiment 1, wherein the antisense strand is 30 or fewer nucleotides in length.
• The composition of embodiment 1, wherein the sense strand and the antisense strand form a duplex region 15 to 30 nucleotide pairs in length.
• The composition of embodiment 1, wherein the antisense strand and the sense strand are independently 19 to 23 nucleotides in length.
• The composition of embodiment 1, wherein the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment.
• The composition of embodiment 1, wherein the RNAi agent comprises at least one modified backbone and/or at least one 2′-modified nucleotide.
• The composition of embodiment 1, wherein the RNAi agent comprises:
• a) at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or
• b) at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide; and/or
• c) at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide; and/or
• d) at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• The composition of embodiment 1, wherein the RNAi agent comprises a 2′-modification selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• The composition of embodiment 1, wherein the RNAi agent comprises a blunt end.
• The composition of embodiment 1, wherein the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• The composition of embodiment 1, wherein the RNAi agent comprises an overhang at the 3′-end of the antisense strand of the RNAi agent.
• The composition of embodiment 1, wherein the RNAi agent is ligated to one or more agent selected from: one or more diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• The composition of embodiment 1, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 60% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 1, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 70% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 1, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 80% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 1, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 90% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 1, wherein the RNAi has an EC50 of no more than about 0.1 nM.
• The composition of embodiment 1, wherein the RNAi has an EC50 of no more than about 0.01 nM.
• The composition of embodiment 1, wherein the RNAi has an EC50 of no more than about 0.001 nM.
• A composition of embodiment 2 is a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the first strand and second strand comprise at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the first and second strand, respectively, of a RNAi agent specific to Beta-Catenin provided in Table 1.
• The composition of embodiment 2, wherein the composition comprises a second RNAi agent to Beta-Catenin.
• The composition of embodiment 2, wherein the second strand is 30 or fewer nucleotides in length.
• The composition of embodiment 2, wherein the first strand and the second strand form a duplex region 15 to 30 nucleotide pairs in length.
• The composition of embodiment 2, wherein the first strand and the second strand are independently 19 to 23 nucleotides in length.
• The composition of embodiment 2, wherein the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment.
• The composition of embodiment 2, wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide.
• The composition of embodiment 2, wherein the RNAi agent comprises:
• at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or at least one 5′-uridine-guanine-3′ (5 ‘-ug-3’) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide;
• and/or at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide;
• and/or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• The composition of embodiment 2, wherein the RNAi agent comprises one or more 2′-modifications selected from the group consisting of:
• 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxy ethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• The composition of embodiment 2, wherein the RNAi agent comprises a blunt end.
• The composition of embodiment 2, wherein the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• The composition of embodiment 2, wherein the RNAi agent comprises an overhang at the 3′-end of the antisense strand.
• The composition of embodiment 2, wherein the RNAi agent is ligated to one or more agents, the agent selected from a: one or more diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• The composition of embodiment 2, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 60% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 2, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 70% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 2, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 80% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 2, wherein the RNAi agent is capable of inhibiting expression of the Beta-Catenin gene by at least about 90% at a concentration of 10 nM in HeLa, GTL-16, or SK-BR-3 cells in vitro.
• The composition of embodiment 2, wherein the RNAi has an EC50 of no more than about 0.1 nM.
• The composition of embodiment 2, wherein the RNAi has an EC50 of no more than about 0.01 nM.
• The composition of embodiment 2, wherein the RNAi has an EC50 of no more than about 0.001 nM.
• A method of embodiment 3 is a method comprising a method of treating a Beta-Catenin-related disease in an individual, comprising the step of administering to the individual a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-Catenin provided in Table 1.
• The method of embodiment 3, wherein the Beta-Catenin-related disease is cancer, autoimmune, or a viral disease.
• The method of embodiment 3, wherein the Beta-Catenin-related disease is cancer.
• The method of embodiment 3, wherein the method further comprises the step of administering an additional treatment for cancer, autoimmune, or a viral disease.
• The method of embodiment 3, wherein the composition comprises a second RNAi agent to Beta-Catenin.
• The method of embodiment 3, wherein the method further comprises the step of administering an additional RNAi agent to Beta-Catenin.
• The method of embodiment 3, further comprising the administration of an additional treatment.
• The method of embodiment 3, wherein the additional treatment is a composition.
• The method of embodiment 3, wherein the additional treatment is a method.
• The method of embodiment 3, wherein the additional treatment and the RNAi agent can be administered in any order.
• A method of embodiment 4 is a method comprising a method of inhibiting the expression of the Beta-Catenin gene in an individual, comprising the step of administering to the individual a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-Catenin provided in Table 1.
• The method of embodiment 4, wherein the individual is afflicted with or susceptible to a Beta-Catenin-related disease.
• The method of embodiment 4, wherein the Beta-Catenin-related disease is cancer, autoimmune, or a viral disease.
• The method of embodiment 4, wherein the Beta-Catenin-related disease is cancer.
• The method of embodiment 4, further comprising the administration of an additional treatment.
• The method of embodiment 4, wherein the additional treatment is a composition.
• The method of embodiment 4, wherein the additional treatment is a method.
• The method of embodiment 4, wherein the additional treatment and the RNAi agent can be administered in any order.
• A composition of embodiment 5 is a composition comprising a medicament for use in an RNAi formulation comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-Catenin provided in Table 1.
• Any composition above in a pharmaceutically effective formulation.
• The composition according to embodiment 5, for use in a method of treating a Beta-Catenin-related disease in an individual, the method comprising the step of administering to the individual a therapeutically effective amount of a composition according to embodiment 1.
• The use of a composition according to embodiment 5, in the manufacture of a medicament for the treatment of a Beta-Catenin-related disease.
• The use of embodiment 5, wherein the Beta-Catenin-related disease is cancer, autoimmune, or a viral disease.
• The composition of embodiment 5, wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.
• The composition of embodiment 5, wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.
ADDITIONAL EQUIVALENTS
• A composition of embodiment 6 is a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-ENaC provided in Table 1.
• The composition of embodiment 6, wherein the composition further comprises a second RNAi agent to Beta-ENaC.
• The composition of embodiment 6, wherein the antisense strand is 30 or fewer nucleotides in length.
• The composition of embodiment 6, wherein the sense strand and the antisense strand form a duplex region 15 to 30 nucleotide pairs in length.
• The composition of embodiment 6, wherein the antisense strand and the sense strand are independently 19 to 23 nucleotides in length.
• The composition of embodiment 6, wherein the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment.
• The composition of embodiment 6, wherein the RNAi agent comprises at least one modified backbone and/or at least one 2′-modified nucleotide.
• The composition of embodiment 6, wherein the RNAi agent comprises:
• a) at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or
• b) at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide; and/or
• c) at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide; and/or
• d) at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• The composition of embodiment 6, wherein the RNAi agent comprises a 2′-modification selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• The composition of cla embodiment 6, wherein the RNAi agent comprises a blunt end.
• The composition of embodiment 6, wherein the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• The composition of embodiment 6, wherein the RNAi agent comprises an overhang at the 3′-end of the antisense strand of the RNAi agent.
• The composition of embodiment 6, wherein the RNAi agent is ligated to one or more agent selected from: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• The composition of embodiment 6, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 60% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 6, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 70% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 6, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 80% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 6, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 90% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 6, wherein the RNAi has an EC50 of no more than about 0.1 nM.
• The composition of embodiment 6, wherein the RNAi has an EC50 of no more than about 0.01 nM.
• The composition of embodiment 6, wherein the RNAi has an EC50 of no more than about 0.001 nM.
• A composition of embodiment 7 is a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the first strand and second strand comprise at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the first and second strand, respectively, of a RNAi agent specific to Beta-ENaC provided in Table 1.
• The composition of embodiment 7, wherein the composition comprises a second RNAi agent to Beta-ENaC.
• The composition of embodiment 7, wherein the second strand is 30 or fewer nucleotides in length.
• The composition of embodiment 7, wherein the first strand and the second strand form a duplex region 15 to 30 nucleotide pairs in length.
• The composition of embodiment 7, wherein the first strand and the second strand are independently 19 to 23 nucleotides in length.
• The composition of embodiment 7, wherein the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment.
• The composition of embodiment 7, wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide.
• The composition of embodiment 7, wherein the RNAi agent comprises:
• at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide;
• and/or at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide;
• and/or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• The composition of embodiment 7, wherein the RNAi agent comprises one or more 2′-modifications selected from the group consisting of:
• 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• The composition of embodiment 7, wherein the RNAi agent comprises a blunt end.
• The composition of embodiment 7, wherein the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• The composition of embodiment 7, wherein the RNAi agent comprises an overhang at the 3′-end of the antisense strand.
• The composition of embodiment 7, wherein the RNAi agent is ligated to one or more agents, the agent selected from a: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• The composition of embodiment 7, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 60% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 7, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 70% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 7, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 80% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 7, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 90% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 7, wherein the RNAi has an EC50 of no more than about 0.1 nM.
• The composition of embodiment 7, wherein the RNAi has an EC50 of no more than about 0.01 nM.
• The composition of embodiment 7, wherein the RNAi has an EC50 of no more than about 0.001 nM.
• A method of embodiment 8 is a method of treating a Beta-ENaC-related disease in an individual, comprising the step of administering to the individual a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-ENaC provided in Table 1.
• The method of embodiment 8, wherein the Beta-ENaC-related disease is cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and/or obesity-associated hypertension.
• The method of embodiment 8, wherein the Beta-ENaC-related disease is cystic fibrosis.
• The method of embodiment 8, wherein the method further comprises the step of administering an additional treatment for cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and/or obesity-associated hypertension.
• The method of embodiment 8, wherein the composition comprises a second RNAi agent to Beta-ENaC.
• The method of embodiment 8, wherein the method further comprises the step of administering an additional RNAi agent to Beta-ENaC.
• The method of embodiment 8, further comprising the administration of an additional treatment.
• The method of embodiment 8, wherein the additional treatment is a composition.
• The method of embodiment 8, wherein the additional treatment is a method.
• The method of embodiment 8, wherein the additional treatment and the RNAi agent can be administered in any order.
• A method of embodiment 9 is a method of inhibiting the expression of the Beta-ENaC gene in an individual, comprising the step of administering to the individual a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-ENaC provided in Table 1.
• The method of embodiment 9, wherein the individual is afflicted with or susceptible to a Beta-ENaC-related disease.
• The method of embodiment 9, wherein the Beta-ENaC-related disease is cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and/or obesity-associated hypertension.
• The method of embodiment 9, wherein the Beta-ENaC-related disease is cystic fibrosis.
• The method of embodiment 9, further comprising the administration of an additional treatment.
• The method of embodiment 9, wherein the additional treatment is a composition.
• The method of embodiment 9, wherein the additional treatment is a method.
• The method of embodiment 9, wherein the additional treatment and the RNAi agent can be administered in any order.
• A medicament for use in an RNAi formulation comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-ENaC provided in Table 1.
• A composition of embodiment 10 is a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand comprises the sequence of the first strand of a RNAi agent specific to Beta-ENaC provided in Table 1.
• The composition of embodiment 10, wherein the composition comprises a second RNAi agent to Beta-ENaC.
• The composition of embodiment 10, wherein the second strand is 30 or fewer nucleotides in length.
• The composition of embodiment 10, wherein the first strand and the second strand form a duplex region 15 to 30 nucleotide pairs in length.
• The composition of embodiment 10, wherein the first strand and the second strand are independently 19 to 23 nucleotides in length.
• The composition of embodiment 10, wherein the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment.
• The composition of embodiment 10, wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide.
• The composition of embodiment 10, wherein the RNAi agent comprises:
• at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide;
• and/or at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide;
• and/or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• The composition of embodiment 10, wherein the RNAi agent comprises one or more 2′-modifications selected from the group consisting of:
• 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• The composition of embodiment 10, wherein the RNAi agent comprises a blunt end.
• The composition of embodiment 10, wherein the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• The composition of embodiment 10, wherein the RNAi agent comprises an overhang at the 3′-end of the antisense strand.
• The composition of embodiment 10, wherein the RNAi agent is ligated to one or more agents, the agent selected from a: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• The composition of embodiment 10, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 60% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 10, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 70% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 10, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 80% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 10, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 90% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 10, wherein the RNAi has an EC50 of no more than about 0.1 nM.
• The composition of embodiment 10, wherein the RNAi has an EC50 of no more than about 0.01 nM.
• The composition of embodiment 10, wherein the RNAi has an EC50 of no more than about 0.001 nM.
• A composition of embodiment 11 is a composition comprising a RNAi agent comprising a first strand and a second strand, wherein the sequence of the first strand is the sequence of the first strand of a RNAi agent specific to Beta-ENaC provided in Table 1.
• The composition of embodiment 11, wherein the composition comprises a second RNAi agent to Beta-ENaC.
• The composition of embodiment 11, wherein the second strand is 30 or fewer nucleotides in length.
• The composition of embodiment 11, wherein the first strand and the second strand form a duplex region 15 to 30 nucleotide pairs in length.
• The composition of embodiment 11, wherein the first strand and the second strand are independently 19 to 23 nucleotides in length.
• The composition of embodiment 11, wherein the RNAi agent comprises a modification that causes the RNAi agent to have increased stability in a biological sample or environment.
• The composition of embodiment 11, wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide.
• The composition of embodiment 11, wherein the RNAi agent comprises:
• at least one 5′-uridine-adenine-3′ (5′-ua-3′) dinucleotide, wherein the uridine is a 2′-modified nucleotide; and/or at least one 5′-uridine-guanine-3′ (5′-ug-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide;
• and/or at least one 5′-cytidine-adenine-3′ (5′-ca-3′) dinucleotide, wherein the 5′-cytidine is a 2′-modified nucleotide;
• and/or at least one 5′-uridine-uridine-3′ (5′-uu-3′) dinucleotide, wherein the 5′-uridine is a 2′-modified nucleotide.
• The composition of embodiment 11, wherein the RNAi agent comprises one or more 2′-modifications selected from the group consisting of:
• 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).
• The composition of embodiment 11, wherein the RNAi agent comprises a blunt end.
• The composition of embodiment 11, wherein the RNAi agent comprises an overhang having 1 to 4 unpaired nucleotides.
• The composition of embodiment 11, wherein the RNAi agent comprises an overhang at the 3′-end of the antisense strand.
• The composition of embodiment 11, wherein the RNAi agent is ligated to one or more agents, the agent selected from a: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.
• The composition of embodiment 11, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 60% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 11, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 70% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 11, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 80% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 11, wherein the RNAi agent is capable of inhibiting expression of the Beta-ENaC gene by at least about 90% at a concentration of 10 nM in H441 cells in vitro.
• The composition of embodiment 11, wherein the RNAi has an EC50 of no more than about 0.1 nM.
• The composition of embodiment 11, wherein the RNAi has an EC50 of no more than about 0.01 nM.
• The composition of embodiment 11, wherein the RNAi has an EC50 of no more than about 0.001 nM.
• A composition of embodiment 12 is any composition above in a pharmaceutically effective formulation.
• The composition according to embodiment 12, for use in a method of treating a Beta-ENaC-related disease in an individual, the method comprising the step of administering to the individual a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-ENaC provided in Table 1.
• The use of a composition according to embodiment 12, in the manufacture of a medicament for the treatment of a Beta-ENaC-related disease.
• The use of a composition according to embodiment 12, wherein the Beta-ENaC-related disease is cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and/or obesity-associated hypertension.
• The composition of embodiment 12, wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.
• The composition of embodiment 12, wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.
• Unless defined otherwise, the technical and scientific terms used herein have the same meaning as that usually understood by a specialist familiar with the field to which the disclosure belongs.
• Unless indicated otherwise, all methods, steps, techniques and manipulations that are not specifically described in detail can be performed and have been performed in a manner known per se, as will be clear to the skilled person. Reference is for example again made to the standard handbooks and the general background art mentioned herein and to the further references cited therein. Unless indicated otherwise, each of the references cited herein is incorporated in its entirety by reference.
• Claims to the invention are non-limiting and are provided below.
• Although particular embodiments and claims have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, or the scope of subject matter of claims of any corresponding future application. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the disclosure without departing from the spirit and scope of the disclosure as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. Those skilled in the art will recognize or be able to ascertain, using no more than routine experimentation, many equivalents of the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims. Redrafting of claim scope in later filed corresponding applications may be due to limitations by the patent laws of various countries and should not be interpreted as giving up subject matter of the claims.

Claims (17)

We claim:

1. A composition for inhibiting the expression of Beta-Catenin, the composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent provided in Table 1, Table 2, or Table 3, and the sense strand is substantially complementary to the antisense strand.

2. The composition ofclaim 1, wherein the composition further comprises a second RNAi agent to Beta-Catenin.

3. The composition ofclaim 1, wherein the RNAi agent comprises at least one modified backbone and/or at least one 2′-modified nucleotide.

4. The composition ofclaim 1, wherein the RNAi agent is ligated to one or more agent selected from: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.

5. The composition ofclaim 1, wherein the RNAi agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises the nucleotide sequence of any of the antisense strand sequences provided in Table 1, Table 2, or Table 3.

6. The composition ofclaim 5, wherein the sense strand comprises the nucleotide sequence of any of the sense strand sequences provided in Table 1, Table 2, or Table 3.

7. The composition ofclaim 5, wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide.

8. The composition ofclaim 1, wherein the RNAi agent is ligated to one or more agents, the agent selected from a: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.

9. A method of treating a Beta-Catenin-related disease in an individual, comprising the step of administering to the individual a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-Catenin provided in Table 1, Table 2, or Table 3.

10. The method ofclaim 9, wherein the Beta-Catenin-related disease is selected from: adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, and chronic wounds and impaired wound healing.

11. The method ofclaim 9, wherein the method further comprises the step of administering an additional treatment for adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, and/or chronic wounds and impaired wound healing.

12. The method ofclaim 11, wherein the method further comprises the step of administering an additional RNAi agent to Beta-Catenin.

13. A method of inhibiting the expression of the Beta-Catenin gene in a subject, the method comprising the step of administering to the subject a therapeutically effective amount of a composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of a RNAi agent specific to Beta-Catenin provided in Table 1 Table 2, or Table 3.

14. The method ofclaim 13, wherein the Beta-Catenin-related disease is adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, and chronic wounds and/or impaired wound healing.

15. The composition according toclaim 1 in a pharmaceutically effective formulation.

16. The composition ofclaim 1, wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.

17. The composition ofclaim 5, wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.

Images