Efficient Ex Vivo Transduction of Pancreatic Islet Cells With Recombinant Adeno-Associated Virus Vectors

The ability to transfer immunoregulatory, cytoprotec-tive, or antiapoptotic genes into pancreatic islet cells may allow enhanced posttransplantation survival of is-let allografts and inhibition of recurrent autoimmune destruction of these cells in type 1 diabetes. However, transient transgene expression and the tendency to induce host inflammatory responses have limited previ-ous gene delivery studies using viral transfer vectors. We demonstrate here that recombinant adeno-associat-ed virus (rAAV) serotype 2, a vector that can overcome these limitations, effectively transduces both human and murine pancreatic islet cells with reporter genes as well as potentially important immunoregulatory cyto-kine genes (interleukin-4, interleukin-10), although a very high multiplicity of infection (10,000 infectiou