AAV8-hAAT-Sirt1

AAV8-hAAT-Sirt1 is a preclinical gene therapy candidate consisting of an adeno-associated virus serotype 8 (AAV8) vector encoding the murine sirtuin 1 (Sirt1) gene under the control of the liver-specific human alpha-1 antitrypsin (hAAT) promoter. Developed by researchers at the Universitat Autònoma de Barcelona and CIBERDEM, the therapy is designed to overexpress SIRT1 specifically in hepatocytes. SIRT1 is a NAD+-dependent protein deacetylase that regulates lipid metabolism, oxidative capacity, and inflammatory responses. In preclinical models of high-carbohydrate diet-induced non-alcoholic fatty liver disease (NAFLD), administration of AAV8-hAAT-Sirt1 reduced hepatic triglyceride accumulation, decreased liver inflammation and macrophage infiltration, and improved systemic insulin sensitivity, suggesting potential therapeutic utility in NAFLD, type 2 diabetes, and metabolic syndrome.