GalNAc-STAT3

GalNAc-STAT3 is an investigational RNA interference (RNAi) therapeutic designed to selectively silence the Signal Transducer and Activator of Transcription 3 (STAT3) gene in hepatocytes. It consists of a Dicer-substrate small interfering RNA (DsiRNA) conjugated to N-acetylgalactosamine (GalNAc), which targets the asialoglycoprotein receptor (ASGPR) for liver-specific uptake. STAT3 is a critical transcription factor that drives inflammation, fibrosis, and oncogenic signaling in the liver microenvironment. Preclinical research presented at AACR 2026 demonstrates that GalNAc-STAT3 can significantly reduce the initiation and burden of hepatocellular carcinoma (HCC) when administered during the early stages of metabolic dysfunction-associated steatohepatitis (MASH). However, the study also indicates a loss of STAT3 dependency once malignant transformation has occurred, suggesting a specific therapeutic window for its use as an early-stage interception strategy rather than a treatment for advanced tumors.

Other names

GalNAc-siSTAT3GalNAc-siSTAT-3GalNAc-siSTAT 3GalNAc-conjugated STAT3 DsiRNA