IN-VIVO NON-VIRAL GENE DELIVERY OF HUMAN VASCULAR ENDOTHELIAL GROWTH FACTOR FOLLOWING ISLET TRANSPLANTATION

摘要

An ultrasound-mediated gene transfer method named Ultrasound Targeted Microbubble Destruction (UTMD) for the delivery of human vascular endothelial growth factor (hVEGF) gene to transplanted islets and the surrounding tissue is described herein. The delivery of hVEGF promotes islet revascularization and survival. The inventors, first transplanted human islets were transplanted into diabetic nude mice liver followed by the induction of non-viral plasmid vectors encoding hVEGF or Green Fluorescent Protein (GFP) gene in the host liver by UTMD. Transplantation without gene delivery was also performed as a control. Blood glucose, serum human insulin, C-peptide levels and the revascularization in graft islets were evaluated. The findings of the method of the present invention indicated that hVEGF gene delivery to host liver using UTMD promoted islet revascularization after islet transplantation and improved the restoration of euglycemia.