To support applications to use state-of-the-art gene modification techniques to develop and test improved beta/islet cell preparations, with a pathway toward therapeutic use in beta cell replacement for T1D patients. At a minimum, the cell preparations must demonstrate safety and functional competence. These should be established through in vitro and in vivo assays that can assess the lack of uncontrolled growth, appropriate insulin production/secretion, and diabetes correction. Off-target editing errors should also be characterized, identified, and minimized. The improved properties of the cell preparations must then be tested in appropriate models to ascertain whether the cells can provide a functional cure in diabetes models with minimal or no chronic immune suppression.