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Generating Improved Beta/Islet Cell Sources through Genetic Modifications

Deadlines are 5:00 PM (Eastern). No extensions will be granted.

Milestone Date Status
Letter of Intent Required Apr 28, 2016 Passed
Application Jul 14, 2016 Passed
Award Notification Oct 31, 2016 Passed
Earliest Start Nov 30, 2016 Passed

Background & Purpose

One of JDRF’s therapeutic goals is to restore beta cell function in type 1 diabetes (T1D) by replacement/transplantation of beta cells/islets. Pancreatic islet transplantation has been efficacious in selected patients in improving metabolic control and quality of life, and in preventing severe hypoglycemia in patients with medically unstable T1D. Despite improvements in cadaveric pancreas procurement, islet isolation, and islet purification, major scientific and technical challenges remain that must be addressed before beta cell replacement could be widely incorporated into the clinical management of established T1D; examples include serious side effects from chronic immunosuppression and the insufficient human islet supply from cadaveric pancreata. JDRF’s role is to enable the scientific community to address these challenges with the ultimate goal of developing safe and effective beta cell replacement approaches available to large numbers of individuals with T1D.

Two alternatives to human cadaveric islets have shown the most promise as clinically applicable commercial beta cell replacement products. Porcine islets represent a readily available, scalable and better quality-controlled cell source. At the same time, many researchers and commercial entities have begun to position human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC) derived pancreatic progenitors or beta/islet cell preparations as potential cellular therapeutics for T1D. It is therefore expected that more than one clinically applicable, manufactured, replenishable beta/islet cell preparation will become a reality in the near future.

Despite great progress made in generating replenishable beta cell sources, the exogenously generated cells will encounter robust allo-, xeno-, and/or auto-immune responses upon transplantation into a T1D patient. Furthermore, the inflammatory transplant environment, metabolic demand, and the lack of immediate vascular access all contribute toward increased stress on implanted insulin-producing cells. An improved beta/islet cell preparation might benefit from genetic engineering to acquire immune privilege and resistance to cell stress. Meanwhile, recent improvements on gene editing techniques, such as the CRISPR-Cas system, offer an unprecedented efficiency and precision in the quest to modify the properties of therapeutic cell products. This RFA wishes to take advantage of these technical advances toward developing improved beta/islet cell products for beta cell replacement therapies for T1D patients.