GalNAc-PNPLA3 siRNA

GalNAc-PNPLA3 siRNA refers to a class of small interfering RNA (siRNA) therapeutics conjugated with N-acetylgalactosamine (GalNAc) designed to target and silence the expression of patatin-like phospholipase domain-containing protein 3 (PNPLA3), particularly the disease-associated I148M genetic variant (rs738409). The PNPLA3 I148M mutation is a major genetic driver of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), leading to impaired triglyceride hydrolysis, lipid droplet accumulation, and progressive hepatic inflammation and fibrosis. By utilizing GalNAc conjugation, these siRNAs specifically target hepatocytes via the asialoglycoprotein receptor (ASGPR), enabling deep and durable gene silencing. Multiple biopharmaceutical companies have developed candidates within this class, including Arrowhead Pharmaceuticals (ARO-PNPLA3), Alnylam Pharmaceuticals (ALN-PNP), Eli Lilly (LY3849891), and a preclinical candidate jointly developed by Sanegene Bio and Hangzhou Zhongmei Huadong Pharmaceutical.

Other names

GalNAc-conjugated siRNA targeting PNPLA3PNPLA3-targeting GalNAc-siRNAPNPLA-3-targeting GalNAc-siRNAPNPLA 3-targeting GalNAc-siRNA