US20260132404
2026-05-14
Chemistry; metallurgy
C12N15/113
The described technology involves modified oligonucleotides and double-stranded RNAs, such as small interfering RNAs (siRNAs). It includes compositions and kits containing these molecules, as well as methods for using them to inhibit target genes. This innovation is particularly relevant to fields requiring enhanced activity and pharmacodynamics of oligonucleotides and siRNAs.
There is an ongoing demand for oligonucleotides and siRNAs with improved characteristics. The current disclosure aims to meet these needs by providing nucleic acids that are more stable and resistant to degradation, thereby enhancing their effectiveness in gene inhibition applications.
The invention introduces a double-stranded nucleic acid, such as dsRNA, which includes an antisense and a sense strand. These strands are complementary and form a double-stranded region with at least 15 base-pairs. Key features include a ligand at the 3′-end of the antisense strand and nuclease resistant modifications at both ends of the strands, enhancing stability against nuclease degradation.
These modifications, which improve the stability of nucleic acids, can include changes to the internucleoside linkage, sugar moiety, or nucleobase. Examples include phosphorothioate or phosphorodithioate linkages, 2′-5′-linked nucleotides, and L-nucleotides. Such modifications reduce the cleavage of nucleic acids by nucleases, thereby increasing their durability in biological systems.
The patent outlines a compound of Formula (I) where various components like B, XS, R5, and others can be modified. These components can include different chemical groups, such as alkyl or heterocyclic groups, which further tailor the properties of the compound for specific applications. This flexibility allows for the creation of molecules with desired characteristics for gene inhibition.