LY3849891

LY3849891 is an investigational small interfering RNA (siRNA) therapeutic designed to target the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, specifically the I148M variant associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD), also known as nonalcoholic fatty liver disease (NAFLD). The drug uses a GalNAc-conjugated siRNA approach to selectively silence PNPLA3 expression in hepatocytes. This precision medicine strategy aims to reduce hepatic fat accumulation and fibroinflammation in patients carrying the PNPLA3 I148M genotype. LY3849891 is being developed by Eli Lilly and was initially developed by Dicerna Pharmaceuticals. It is currently undergoing Phase 1 clinical trials for safety and tolerability in MASLD/NAFLD patients with the PNPLA3 I148M genotype[1][2][4][5].