PNPLA3 antisense oligonucleotide

PNPLA3 antisense oligonucleotides (ASOs) are a class of nucleic acid-based therapeutics designed to selectively reduce the expression of the patatin-like phospholipase domain-containing protein 3 (PNPLA3). These agents primarily target the PNPLA3 I148M variant (rs738409), a major genetic risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). By binding to PNPLA3 mRNA and inducing its degradation via RNase H, these ASOs aim to decrease hepatic fat accumulation and prevent the progression of liver fibrosis. The most advanced candidate in this class is AZD2693 (also known as IONIS-PNPLA3-LRx), developed by AstraZeneca and Ionis Pharmaceuticals, which is currently in Phase II clinical trials (e.g., the FORTUNA study) and utilizes N-acetylgalactosamine (GalNAc) conjugation for targeted delivery to hepatocytes.

Other names

PNPLA3 ASOPNPLA-3 ASOPNPLA 3 ASOPNPLA3-targeting antisense oligonucleotidePNPLA-3-targeting antisense oligonucleotidePNPLA 3-targeting antisense oligonucleotide