Type I Diabetes Mellitus Gene Therapy

Type I diabetes mellitus (T1DM) affects more than 17 million people worldwide, and current treatments for T1DM, known as insulin therapy, require continued insulin injection, diet control, and constant monitoring of blood sugar. While gene therapy methods that restore insulin production in non-pancreatic cells might provide a one-shot cure for T1DB. We propose a gene therapy for T1DM using an adeno-associated viral (AAV) vector that transfects somatic cells with an insulin gene controlled by a glucose-sensitive promoter, thus potentially able to restore glucose-regulated insulin production in diabetic patients. Preliminary testing will be conducted on cell lines to assess the efficiency of the therapy.
With the aim of restoring insulin production in T1DM patients, we propose to genetically modify non-beta cells to produce insulin at high glucose concentration. An engineered AAV vector will deliver the insulin production system into 293 cell lines to be tested. The insulin gene has been cloned and modified to allow for efficient proteolytic cleavage in non-beta cells (furin). In initial tests mCherry will be used instead of insulin as a reporter, and the effect will be assessed using FACS and microscopy.

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