Modified unlocked nucleic acid (MUNA) mitigates off-target effects of small interfering RNAs.

ABSTRACT: Unlocked nucleic acid (UNA) is a nucleic acid analog that has an acyclic ribose ring lacking the bond between C2' and C3' atoms. The base-pairing properties of UNA have been studied, and it has been used as a scaffold for conjugation, but the chemical space around UNA and its potential applications in the context of short interfering RNAs (siRNAs), which mediate RNA interference, have not been thoroughly explored. In this study, we report syntheses of methylated and methoxylated UNAs and their incorporation into siRNAs. siRNAs with 5'-(R)-methyl-UNA and with 5'-(S)-methyl-UNA in the seed region had comparable potencies but reduced off-target effects compared to siRNA modified with UNA. In mice, siRNAs with modified UNAs were of comparable potency to an siRNA of the same sequence and chemis

SUBMITTER: Mori S 

PROVIDER: S-EPMC12477598 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature