Development of platforms for sorting, production, editing of beta cells

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PROJECT SUMMARY Patients suffering from type 1 diabetes must undergo burdensome, often lifelong, exogenous insulin dependence. Up to now, the only available replacement therapy is to transplant islets from cadaveric donors. However, such procedures present hurdles such as the scarcity of available donors and the rejection of transplanted cells by the patient’s immune system. Also, over time, the transplanted islets tend to die. Several types of stem cells, including embryonic stem cell and induced pluripotent stem cell, have been extensively studied to generate glucose-responsive insulin-secreting cells and represents a more tenable source of islets. However, a significant concern for transplantation therapy is the need for immunosuppressive drugs, which exhibit long term side effects and hinders the feasibility of this approach to the large population of T1D patients. Furthermore, cost-effective and large-scale production of these stem cell-derived beta cells is still a major challenge. We propose to apply chemical biology and genome engineering approaches to develop platforms for efficient sorting, production, and editing of these beta cells. PHS 398/2590 (Rev. 06/09) 1 Continuation Format Page