Improved In Vivo Metabolic Stability and Silencing Efficacy of siRNAs with Phosphorothioate Linkage-Free, GalNAc-Conjugated Sense Strands Containing Morpholino-LNA Modifications.

ABSTRACT: To ensure specificity, loading of the sense strand of small interfering RNAs (siRNAs) into RISC must be inhibited. We show here that siRNAs with 5'- and 6'-morpholino LNA residues or 6'-OH-LNA at the 5' terminus of a fully phosphodiester sense strand resulted in metabolically stable siRNAs with a potency and a duration of action in mice that were greater than those of an siRNA in which the 5' terminus of the sense strand has two terminal phosphorothioate linkages and regular LNA.

SUBMITTER: Datta D 

PROVIDER: S-EPMC11613684 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature