Table 1.

Gene-replacement therapies for epidermolysis bullosa in clinical trials

Gene therapy trial	EB type/protein	Approach	Participants (N)	Results	References
Phase I	JEB/laminin β3 chain	Ex vivo genetically corrected (retroviral) autologous epidermal grafts	2	One 7-year-old child treated in wounds covering 80% of the total body surface resulted in regeneration of entire epidermis by transgenic stem cells stable over several years. One 49-year-old woman was successfully treated on an 80 cm2 chronic wound	[35, 36]
Phase I/II; NCT03490331 (HOLOGENE17)	JEB/C17	Ex vivo grafting of gene‐corrected epidermal sheets with a gamma‐retroviral vector carrying COL17A1 cDNA	12	Ongoing	[91] https://clinicaltrials.gov/ct2/show/NCT03490331
Phase I/II; NCT02984085 (HOLOGENE7)	RDEB/C7	Ex vivo grafting of gene‐corrected epidermal sheets with a gamma‐retroviral vector carrying COL7A1 cDNA	12	Ongoing	[91] https://clinicaltrials.gov/ct2/show/NCT02984085
Phase I; safety and wound outcomes; single center	RDEB/C7	Ex vivo genetically corrected (retroviral) autologous epidermal grafts of 35 cm2	4	Variable response of wound healing and C7; generally declined over 1 year	[30]
Phase I/IIa; single center	RDEB/C7	Ex vivo genetically corrected (retroviral) autologous epidermal grafts of 35 cm2	7	C7 expression persisted up to 2 years after treatment in two participants. Treated wounds with ≥ 50% healing demonstrated improvement in patient-reported pain, itch, and wound durability	[29]
Phase I; single center	RDEB/C7	Three intradermal injections (~ 1 × 106 cells/cm2 of intact skin) of COL7A1-modified (lentiviral) autologous fibroblasts	4	C7 restoration in vivo in treated skin at 1 year after gene therapy	[92]
Phase I/II, phase III; NCT04213261 (Castle Creek Biosciences, Inc.)	RDEB/C7	COL7A1-corrected autologous fibroblasts injected in the wounds	20	Ongoing	https://clinicaltrials.gov/ct2/show/NCT04213261
Phase III; NCT04227106 (Abeona Therapeutics Inc.)	RDEB/C7	Transplantation of ex vivo COL7A1-corrected autologous keratinocyte sheets	15	Ongoing	https://clinicaltrials.gov/ct2/show/NCT04227106
Phase I/II; European (GENEGRAFT)	RDEB/C7	Skin-equivalent grafts ex vivo genetically corrected with a COL7A1-encoding SIN retroviral vector	4	Ongoing	[33]
Phase I/II; NCT03536143 (Krystall Biotech, Inc.)	RDEB/C7	Topically administered, replication-deficient HSV-1 vector containing two functional COL7A1 genes applied directly to wounds	6	Ongoing	www.krystalbio.com/focus/about-dystrophic-eb/
Phase I (Amryt Pharma, PLC)	RDEB/C7	Topically administered synthetic polymer polyplexes containing COL7A1, applied directly to wounds	NA	NA	https://www.amrytpharma.com/patients-and-carers/gene-therapy/

cDNA complementary DNA, C7 type VII collagen, C17 type XVII collagen, EB epidermolysis bullosa, HSV-1 herpes simplex virus type 1, JEB junctional EB, NA not available, RDEB recessive dystrophic EB, SIN self-inactivating