Recent advance in hepatic insulin gene therapy

The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic cells by autoimmune responses specific to cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific l-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here, we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.