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Gene Therapy (2015) 22, 18 2015 Macmillan Publishers Limited All rights reserved 0969-7128/15
http://www.nature.com/gt
Web End =www.nature.com/gt
REVIEW
The use of -cell transcription factors in engineering articial cells from non-pancreatic tissue
D Gerace1,3, R Martiniello-Wilks1,2,3, BA OBrien1 and AM Simpson1
Type 1 diabetes results from the autoimmune destruction of the insulin-producing pancreatic beta () cells. Patients with type 1 diabetes control their blood glucose levels using several daily injections of exogenous insulin; however, this does not eliminate the long-term complications of hyperglycaemia. Currently, the only clinically viable treatments for type 1 diabetes are whole pancreas and islet transplantation. As a result, there is an urgent need to develop alternative therapies. Recently, cell and gene therapy have shown promise as a potential cure for type 1 diabetes through the genetic engineering of articial cells to regulate blood glucose levels without adverse side effects and the need for immunosuppression. This review compares putative target cells and the use of pancreatic transcription factors for gene modication, with the ultimate goal of engineering a glucose-responsive
articial cell that mimics the function of pancreatic cells, while avoiding autoimmune destruction.
Gene Therapy (2015) 22, 18; doi:http://dx.doi.org/10.1038/gt.2014.93
Web End =10.1038/gt.2014.93 ; published online 23 October 2014
INTRODUCTIONType 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing pancreatic beta () cells, resulting in hyperglycaemia.1 Currently, patients with T1D control their blood glucose levels using several daily injections of exogenous insulin;2 however, this does not mimic the exquisite metabolic responsiveness of the cell. Insulin therapy delays, but does not eliminate hyperglycaemic episodes and chronic complications associated with extended periods of hyperglycaemia.3,4 Of equal,
if not more, concern to the patient are the life-threatening hypoglycaemic episodes that are exacerbated because of hypoglycaemia unawareness, a phenomenon that worsens with both disease duration and maintenance of blood glucose levels close to normal values.4
Currently, whole pancreas or islet transplantation are the only clinically viable treatments for T1D. However, they are limited by a shortage of pancreas donors and the requirement for lifelong immunosuppression, which carries adverse side effects and can compromise the survival of transplanted tissue.5 Developing cell and gene therapy strategies show immense promise as alternate therapies, potentially avoiding both the requirement for immuno-suppression and recurrent autoimmunity.
Over the past decade, there have been...