Replacement of lost pancreatic islets with cadaver-derived islets has proven to be a successful functional cure for some type 1 diabetes (T1D) patients, allowing them to become independent of exogenous insulin. However, the limited supply of human islet donors, along with the challenges associated with life-long immunosuppression, have restricted widespread use of islet transplantation. Human pluripotent stem cells (hPSCs) represent a renewable and expandable cell source with a demonstrated capacity to differentiate into insulin-producing cells for treating insulin-dependent diabetes. In recent years, cell therapies for T1D using hPSCs have moved from the lab into the clinic, and their potential to produce insulin in patients has been demonstrated. The combination of hPSCs with gene editing technologies such as CRISPR/Cas9 have allowed for cellular manipulation that is hypothesized to allow the cells to become invisible from the immune system and to potentially improve their cell fitness. In partnership with ViaCyte, we have initiated clinical evaluation of gene-edited pancreatic progenitor cells that have been designed to avoid host immune system recognition and to have improved cell fitness and survival post-transplant. Thus, the goal of functionally curing T1D without immunosuppression may become a reality.