ApoC3 siRNA prototype

The ApoC3 siRNA prototype is a preclinical RNA interference (RNAi) therapeutic candidate developed by Alnylam Pharmaceuticals. It utilizes the company's proprietary GalNAc-siRNA platform, which features a N-acetylgalactosamine (GalNAc) ligand conjugated to a chemically modified siRNA to facilitate targeted delivery to hepatocytes via the asialoglycoprotein receptor (ASGPR). The molecule is designed to silence the expression of Apolipoprotein C-III (ApoC3), a protein that inhibits lipoprotein lipase and hepatic lipase, thereby playing a critical role in triglyceride metabolism. In preclinical studies using db/db mouse models of hypertriglyceridemia, the prototype demonstrated high potency with an ED90 for ApoC3 protein reduction of less than 2.5 mg/kg and a 50% reduction in serum triglycerides.