Gene Therapy Progress and Prospects: Gene therapy for diabetes mellitus

Abstract

Diabetes mellitus has long been targeted, as yet unsuccessfully, as being curable with gene therapy. The main hurdles have not only been vector-related toxicity but also the lack of physiological regulation of the expressed insulin. Recent advances in understanding the developmental biology of b-cells and the transcriptional cascade that drives it have enabled both in vivo and ex vivo gene therapy combined with cell therapy to be used in animal models of diabetes with success. The associated developments in the stem cell biology and immunology have opened up further opportunities for gene therapy to be applied to target autoimmune diabetes.

Widespread and Stable Pancreatic Gene Transfer by Adeno-Associated Virus Vectors via Different Routes

“…Diabetes 55: [875][876][877][878][879][880][881][882][883][884]2006 N ovel therapeutics, including gene therapy, are vigorously being sought to treat diabetes. Previous gene therapy studies on diabetes were mainly focused on the ex vivo approaches to modify the islets for transplantation (1)(2)(3)(4)(5)(6)(7). The in vivo approaches were mostly targeted toward the nonpancreatic tissues such as the liver and muscle for ectopic ␤-cell neogenesis (8,9), insulin production (10,11), and modulation of immune responses (12,13).…”

The status of gene vectors for the treatment of diabetes

“…The rationale for genetic approaches to DT1 include four basic approaches: suppression of autoimmunity, replacement of a physiologic insulin response, replacement of islets per se, and correction of the vascular and nerve damage associated with the disease [2]. Genetic approaches have been proposed aimed at curtailment of the immune activation and islet cell destruction [3][4][5][6].…”

Rationally Designed Synthetic Vectors for Gene Delivery

“…Originally it was targeted towards treatment of inheritable single-gene disorders caused due to an absent or defective gene. However, applications of gene therapy have expanded to include treatment of acquired and infectious diseases and exogenously administered genes now are used in a wide variety of applications including immunomodulation, genetic vaccination and genetic pharmacology [1][2][3][4][5][6].…”