895. Ex Vivo Gene Therapy of Metabolic Liver Disorders Using Uncultured and Lentivirally Transduced Hepatocytes

Abstract

Background: At the present time, orthotopic liver transplantation is the only effective therapy for several congenital and acquired hepatic disorders. Because of a chronic organ shortage, and of the necessity of heavy and lifelong immunosuppression after transplantation, gene therapy represents a promising alternative. We have previously described an ex vivo gene therapy protocol that allows very high rates of transduction of human hepatocytes (up to 98%), in which freshly isolated hepatocytes are transduced in suspension and immediately transplanted. This protocol is easily performed, rapid, does not required primary culture of hepatocytes, and preserves full cell engraftment potential and in vivo cell functionality. In this study, we used the Gunn rat, which is the model for Crigler-Najjar syndrome type I, a defect in bilirubin UDP-glucuronyltransferase (BGT), to evaluate our approach.