Advances and potential of gene therapy for type 2 diabetes mellitus

Abstract

Gene therapy of type 2 diabetes mellitus (T2DM) and its complications has attracted intensive interest in recent years. In this paper, we critically review literature reports on gene therapy of T2DM published over the last five years. By reviewing these advances, three questions were addressed. First, which genes and how do they exert anti-diabetic effects? Target genes including that regulating glucose homeostasis, improving insulin secretion or sensitivity, and ameliorating diabetic induced complications are summarized. Second, how to deliver and which route is advantageous? All main methods that have been used for delivery of target genes into diabetic subjects are outlined and discussed regarding their pros and cons. Last, what are the future directions and how do these advances promote the study of T2DM gene therapy? Testing of novel targets in a parallel way and especially, using combinational approaches may be the main directions. In conclusion, there are a large number of genes playing important roles during the incidence and development of T2DM, and many of them hold great promise as potential targets for gene therapy. Oral delivery of target genes by probiotics may be a nice route with priority to develop, due to its high efficiency and safety for future gene therapy of T2DM.