Adeno-Associated Virus Gene Therapy for Diabetes and Obesity

This invention is directed to adeno-associated virus (AAV) vector delivery of exendin-4 (Ex-4) to salivary glands as treatment for diabetes and obesity. Ex-4 is a potent and long-acting agonist of the receptor for glucagon-like peptide 1 (GLP-1). Scientists at NIDCR have shown that AAV-mediated delivery of Ex-4 resulted in improved glucose homeostasis and weight profile in two rat models of obesity and type 2 diabetes. Further, AAV-mediated delivery of Ex-4 to rat salivary glands resulted in localized and sustained expression of Ex-4 that was biologically active and well tolerated.

AAV-mediated delivery of Ex-4 is superior to administering GLP-1 analogs in that AAV-Ex-4 expression is more stable and longer acting. Like GLP-1 analogs, Ex-4 expression also potentially provides beneficial effects like reduced hypoglycemia, appetite suppression, and potential weight loss.