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.

Potential Commercial Applications: Competitive Advantages:
  • Therapy for diabetes or obesity.
  • Potential for potent glucose homeostasis therapy with longer duration than current drugs.
  • More convenient than daily or weekly injections.

Development Stage:
  • Early-stage
  • In vitro data available
  • In vivo data available (animal)


John Chiorini (NIDCR)  ➽ more inventions...

Giovanni Di Pasquale (NIDCR)  ➽ more inventions...

Edward Mannucci

Intellectual Property:
US Pat: 10,300,095 issued 2019-05-28
US Pat: 9,511,103 issued 2016-12-06
PCT Application No. PCT/US12/34268 filed on 2012-04-19
US Application No. 14/112,790 filed on 2014-03-20
US Application No. 16/396,262 filed on 2019-04-26

Di Pasquale G, et al. PMID 22808093

Collaboration Opportunity:

The NIDCR is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize treatment of diabetes by expression NGF-extendin 4 protein. For collaboration opportunities, please contact David Bradley, Ph.D. at 301-402-9242 or

Licensing Contact:
Vladimir Knezevic, M.D.
Phone: 301.443.5560

OTT Reference No: E-142-2011-0
Updated: Nov 2, 2016