GENE TRANSFER TO PANCREATIC B CELLS FOR PREVENTION OF ISLET DYSFUNCTION

摘要

The present invention relates to methods and compositions for inhibiting pancreatic beta cell dysfunction and Fas-mediated apoptosis. The invention relates to recombinant vectors, including viral vectors, comprising nucleic acids molecules encoding inhibitors of interleukin-1beta (IL-1beta) and Fas-mediated apoptosis and the use of such vectors for transfer of said nucleic acid molecules into beta cells. The invention encompasses genetically engineered beta cells comprising nucleic acid molecules encoding inhibitors of IL-1beta signal transduction. The invention further relates to methods for transplanting such genetically engineered beta cells into a host recipient with a pancreatic disorder. The methods and compositions of the invention may be used to reduce Il-1beta mediated beta cell dysfunction and apoptosis, thereby reducing the insulitis associated with pancreatic disorders such as insulin dependent diabetes mellitus (IDDM).