833 Ex vivo gene therapy of recessive dystrophic epidermolysis bullosa skin cells leads to dermo-epidermal adhesion strength restoration in autologous bilayered self-assembled skin substitutes

Although gene therapy shows great promises for the treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB), a rare genodermatosis (3/million births) in which minor mechanical stress to skin results blisters and scarring leading severe pain, permanent restoration normal type VII collagen (C7) by genetically modified cells remains challenge. Here, we investigate potential combined with autologous bilayered substitutes. Viral transduction efficiency C7 RDEB fibroblasts gamma-retrovirus was improved 2.6 folds (p<.05) when using EF-c peptide compared polybrene did not affect proliferation keratinocytes stem cell content whereas led decrease both (-20% -33%, respectively (p<.01)). Overall, restored production 55% 65% keratinocytes. Skin substitutes produced various combinations untreated corrected showed that before grafting allows higher deposition Quantitative adhesion strength dermo-epidermal junction (DEJ) comparable properties healthy (2.9mN/mm) those (3.9mN/mm), but (1.5mN/mm). After on athymic mice, at DEJ were maintained least 11 months. grafting, surface area increased 4 In conclusion, self-assembly approach as long-term wounds.