Ribofuranose-based GalNAc-conjugated siRNA enhances the liver-targeted delivery and elicits robust RNAi-mediated gene silencing.

ABSTRACT: The N-acetylgalactosamine (GalNAc)-conjugate delivery platform has emerged as a pivotal enabling technology for the clinical translation of oligonucleotide therapeutics. The development of GalNAc-conjugated small interfering RNA (siRNA) therapeutics has been significantly advanced through structural optimization of the delivery platform. Here, we report that a series of ribofuranose- and deoxyribofuranose-incorporated GalNAc-siRNA conjugates targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA were synthesized and evaluated for their bioactivities and tissue distribution in vivo. When compared in detail with inclisiran, an approved siRNA drug that incorporates a triantennary GalNAc construct (designated L96) for targeted liver delivery, inc-G5, which contains

SUBMITTER: Huang ZA 

PROVIDER: S-EPMC12800395 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature