aav8-gnmt

AAV8-GNMT is a gene therapy construct that uses the adeno-associated virus serotype 8 (AAV8) vector to deliver the human glycine N-methyltransferase (GNMT) gene specifically to liver cells (hepatocytes)[1][2]. GNMT is abundantly expressed in normal liver tissue and plays a protective role against tumor formation and liver damage; its depletion is associated with progression of hepatocellular carcinoma (HCC) and liver cirrhosis[1][2]. The AAV8-GNMT construct is designed to restore or enhance GNMT expression in the liver, thereby downregulating pro-inflammatory and pro-fibrotic responses, reducing liver injury and fibrosis, and delaying the development of HCC in preclinical models[1][2]. The therapy is administered via injection (likely intravenous or intraportal), and the transgene expression is long-lasting, with detectable effects for up to 11 months in mice[2]. In animal models, AAV8-GNMT has been shown to reduce levels of liver injury markers (ALT, AST), pro-inflammatory cytokines (TNF-α, IL-6), pro-fibrotic markers (α-SMA, desmin, TGF-β1, TIMP1, collagen I, MMP13), and to attenuate tumor growth and reduce the incidence of HCC[1][2]. No significant adverse effects on liver function or morphology were observed in treated mice during long-term follow-up[2]. This experimental therapy is primarily being investigated as a potential treatment for liver diseases, particularly those involving GNMT deficiency, chronic inflammation, fibrosis, and HCC[1][2].