siRNA

Overview

Double-stranded RNA molecules that silence gene expression by degrading target mRNA in the cytoplasm; the dominant modality for liver-targeting drugs delivered via GalNAc conjugates, with growing application in CNS via TFR1 targeting. siRNA is double-stranded and acts in the cytoplasm (unlike ASOs that reach the nucleus); it tends to have lower toxicity than early-generation ASOs and has been predominantly deployed for liver targets via GalNAc conjugate delivery. As of 2026, virtually all approved siRNA drugs target the liver predominantly using GalNAc conjugates; Alnylam is the leading commercial player, and every siRNA product visible in the current clinical landscape targets liver. (Segment 2 (05:00-10:00))