173. Adenovirus-mediated gene transfer to mouse and dog pancreas in vivo (original) (raw)

2004, Molecular Therapy - MOL THER

Type 1 diabetes results from autoimmune destruction of pancreatic β cells. This process might be reverted by genetically engineering endocrine pancreas in vivo to express factors that induce β-cell replication and neogenesis and counteract the immune response. However, the pancreas is difficult to manipulate and pancreatitis is a serious concern, which has made effective gene transfer to this organ elusive. Thus, new approaches for gene delivery to pancreas in vivo are required. Here we show that mouse pancreatic β-cells were efficiently transduced, and they expressed β-galactosidase after systemic injection of adenovirus with clamped hepatic circulation. Seven days after vector administration about 70% of pancreatic islets showed β-gal expression. In these islets, about 20% of the β-cells were transduced by the adenoviruses. Furthermore, scattered acinar cells expressing β-gal were also observed. In addition to mouse, we also examined the ability of adenovirus to transduce dog panc...