AU2024269222A1 - Circular rna compositions and methods - Google Patents

Abstract

Circular RNA and precursor RNA polynucleotides, along with related compositions and methods are described herein. In some embodiments, the circular RNA comprises, in the following order, a 3' self-spliced exon segment, an intervening region, and a 5' self-spliced exon segment. In some embodiments, the precursor RNA is a linear RNA comprising a 5' combined accessory element comprising a 3' permuted intron segment; an intervening region; and a 3' combined accessory element comprising a 5' permuted intron segment. In some embodiments, the circular RNA and/or precursor RNA polynucleotides comprise a coding region comprising an expression sequence. In some embodiments, the precursor RNA polynucleotide comprises a monotron. In some embodiments, the circular RNA has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, the methods and constructs result in improved circularization efficiency and/or splicing efficiency as compared to a control RNA polynucleotide comprising a native intronic sequence. Also provided herein are precursor RNA polynucleotides, circular RNA polynucleotides, and DNA polynucleotides, including polynucleotides comprising at least one modified A, C, G, or U nucleotide or nucleoside. Also presented herein are methods and compositions for the manufacture and preparation of circularized RNAs, along with methods of administering said circular RNAs and related compositions to a subject in need thereof for treatment or prevention purposes.