{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:10:35Z","timestamp":1793405435228,"version":"4.5.0"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"11","funder":[{"name":"CureEB","award":["McGrath20LENTICOL-F"],"award-info":[{"award-number":["McGrath20LENTICOL-F"]}]},{"DOI":"10.13039\/100008081","name":"Dystrophic Epidermolysis Bullosa Research Association","doi-asserted-by":"crossref","award":["McGrath20LENTICOL-F"],"award-info":[{"award-number":["McGrath20LENTICOL-F"]}],"id":[{"id":"10.13039\/100008081","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,6]]},"abstract":"\n BACKGROUND<\/jats:title>\n \n Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of skin fragility disorder due to mutations in\n COL7A1<\/jats:italic>\n encoding basement membrane type VII collagen (C7), the main constituent of anchoring fibrils (AFs) in skin. We developed a self-inactivating lentiviral platform encoding a codon-optimized\n COL7A1<\/jats:italic>\n cDNA under the control of a human phosphoglycerate kinase promoter for phase I evaluation.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n In this single-center, open-label phase I trial, 4 adults with RDEB each received 3 intradermal injections (~1 \u00d7 10\n 6<\/jats:sup>\n cells\/cm\n 2<\/jats:sup>\n of intact skin) of\n COL7A1<\/jats:italic>\n -modified autologous fibroblasts and were followed up for 12 months. The primary outcome was safety, including autoimmune reactions against recombinant C7. Secondary outcomes included C7 expression, AF morphology, and presence of transgene in the injected skin.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Gene-modified fibroblasts were well tolerated, without serious adverse reactions or autoimmune reactions against recombinant C7. Regarding efficacy, there was a significant (\n P<\/jats:italic>\n < 0.05) 1.26-fold to 26.10-fold increase in C7 mean fluorescence intensity in the injected skin compared with noninjected skin in 3 of 4 subjects, with a sustained increase up to 12 months in 2 of 4 subjects. The presence of transgene (codon-optimized\n COL7A1<\/jats:italic>\n cDNA) was demonstrated in the injected skin at month 12 in 1 subject, but no new mature AFs were detected.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n To our knowledge, this is the first human study demonstrating safety and potential efficacy of lentiviral fibroblast gene therapy with the presence of\n COL7A1<\/jats:italic>\n transgene and subsequent C7 restoration in vivo in treated skin at 1 year after gene therapy. These data provide a rationale for phase II studies for further clinical evaluation.\n <\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION<\/jats:title>\n ClincalTrials.gov NCT02493816.<\/jats:p>\n <\/jats:sec>\n \n FUNDING<\/jats:title>\n Cure EB, Dystrophic Epidermolysis Bullosa Research Association (UK), UK NIHR Biomedical Research Centre at Guy\u2019s and St Thomas\u2019 NHS Foundation Trust and King\u2019s College London, and Fondation Ren\u00e9 Touraine Short-Exchange Award.<\/jats:p>\n <\/jats:sec>","DOI":"10.1172\/jci.insight.126243","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T11:01:16Z","timestamp":1559732476000},"source":"Crossref","is-referenced-by-count":80,"title":["Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3325-3675","authenticated-orcid":true,"given":"Su M.","family":"Lwin","sequence":"first","affiliation":[{"name":"St John\u2019s Institute of Dermatology, School of Basic and Medical Biosciences, King\u2019s College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhatullah","family":"Syed","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-1649","authenticated-orcid":true,"given":"Wei-Li","family":"Di","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tendai","family":"Kadiyirire","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, School of Basic 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