Type 1 diabetes mellitus (T1DM) is a disease characterized by chronically elevated blood glucose levels that results from the autoimmune destruction of the insulin-producing β cells of the pancreas. While treatment options exist, they all possess serious limitations. Insulin gene therapy provides a promising alternative aimed at replacing insulin production in native non-β cells. For insulin gene therapy applications to be successful in treating T1DM, a glucose-sensitive organ must be targeted for insulin expression, insulin production must be responsive to ever-changing blood glucose levels, and insulin expression must persist long term. In addition, the amount of insulin production is critical, as too little insulin would lead to poor glucose regulation and too much insulin would induce hypoglycemia, a potentially life-threatening state. Together, insulin gene therapy provides challenges that are absent with other gene therapy applications. In this chapter, we examine the challenges of insulin gene therapy and discuss how the two key components of insulin gene therapy—the insulin expression cassette and the delivery vehicle—can be tailored for the successful treatment of T1DM.
Part of the book: Modern Tools for Genetic Engineering