Precision Genome Editing for Monogenic Diabetes

Precision Genome Editing for Monogenic Diabetes: Therapeutic Correction of Genetic Defects in Beta Cells and Establishment of a Comprehensive Safety Framework

Certain types of diabetes result from a single defective gene that causes the insulin-producing cells of the pancreas to function incorrectly. Existing medications can regulate sugar in the blood but do nothing to address the condition. In this particular project, we will use an accurate gene editing tool named base editing to fix Diabetes-causing gene mutations. We will do this on lab-engineered human stem cell-derived pancreatic islet cells that have been transplanted into diabetic mice, and on diabetic mice models.

We will investigate how well this corrects the genetic problem and whether it leads to a return of insulin production and health of cells that produce insulin. Equally important is that we assess safety, how these tools of gene editing are distributed within the body, whether they trigger any secondary changes within the genes, and how they are accepted by the body’s immune system. The study helps lay the groundwork for the development of safer and more long-lasting therapies that tackle the immediate cause of inherited diabetes.