Year 3

Recessive Dystrophic Epidermolysis Bullosa (RDEB) patients suffer from severe depletion or exhaustion of epidermal stem cells from chronic wounding that prevent the scalability needed to meet the long term needs of patients.  We have now developed a scalable alternative strategy using COL7A1-corrected keratinocyte grafts derived from autologous induced pluripotent stem cells (iPSCs) called RDEB Cell Therapy or DEBCT.Our group’s initial DEBCT manufacturing effort funded by CIRM DR1-01454, DEBCT2014, demonstrated our ability to generate autologous COL7A1-corrected iPS-derived graftable human keratinocytes. This proof-of-concept pre-clinical study showed our ability to correct mutations at different sites within the COL7A1 locus to make COL7A1-corrected iPSCs, and the ability to generate graftable keratinocytes from different iPS lines, revealing the robustness and clinical readiness of the therapy.  However, DEBCT2014 suffered from complex manufacturing issues including integrating vectors for reprogramming or correction, the requirement for multiple clonal steps to generate corrected iPSCs, and the use of murine feeders.Through the funding of this CIRM Tools award and the work of the multi-center EB iPS Consortium, we have manufactured DEBCT using DEBCT2017 that we are moving into clinical development.