{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:06:39Z","timestamp":1788933999601,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dystrophic epidermolysis bullosa (DEB) is a rare, debilitating genodermatosis caused by loss\u2010of\u2010function variants in\n                    <jats:italic>COL7A1,<\/jats:italic>\n                    resulting in type VII collagen (C7) deficiency and defective anchoring fibrils, which are essential for dermal\u2013epidermal adhesion.\n                    <jats:italic>COL7A1<\/jats:italic>\n                    is a large gene, and C7 is synthesized by both keratinocytes and fibroblasts, and extracellularly secreted, where it forms a supramolecular network that stabilizes the dermal\u2013epidermal junction. Human genotype\u2013phenotype correlations suggest that residual C7 expression (~10% of normal levels) may confer a milder disease phenotype, whereas complete absence results in generalized skin fragility with scarring and systemic complications. Thus, restoring C7 expression remains a central therapeutic objective. Since the discovery of\n                    <jats:italic>COL7A1<\/jats:italic>\n                    , thousands of pathogenic variants have been described, including amino acid substitutions in the triple\u2010helical domain that allow partial C7 function, whereas null alleles are associated with severe phenotypes. Gene\u2010 and cell\u2010based strategies have evolved to address the large\n                    <jats:italic>COL7A1<\/jats:italic>\n                    size and delivery challenges. Ex\u00a0vivo gene\/cell therapies (keratinocytes or fibroblasts engineered to express\n                    <jats:italic>COL7A1<\/jats:italic>\n                    ) have demonstrated partial, wound\u2010specific C7 restoration but with durability limitations, as grafted cells may be outcompeted or lose transgene expression over time; select patients show sustained anchoring fibril formation and improved wound healing; however, long\u2010term outcomes remain variable. In\u00a0vivo topical gene therapy has achieved clinically meaningful wound closure in DEB, illustrating a paradigm shift toward accessible and patient\u2010friendly therapeutic approaches, albeit with real\u2010world considerations on durability and wound recurrence. A multidisciplinary framework integrating EB expert centers, drug\u2010delivery pharmacy services, wound management, and patient\u2010support programs can further enhance treatment access and adherence. General factors such as nutritional status, infection and comorbidities also influence both wound healing and the response to gene therapy. Revertant mosaicism offers a natural gene\u2010therapy substrate: cultured epidermal autografts derived from revertant patches have yielded substantial, yet heterogeneous, epithelization, with outcomes contingent on revertant cell proportion and culture fidelity. Collectively, these advances highlight the emerging potential of gene\u2010 and cell\u2010based therapies to achieve durable disease modification in DEB.\n                  <\/jats:p>","DOI":"10.1111\/exd.70339","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T03:22:21Z","timestamp":1786159341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene Therapy for Dystrophic Epidermolysis Bullosa"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-507X","authenticated-orcid":false,"given":"Cristina","family":"Has","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine and Medical Center University Hospital Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1067-8582","authenticated-orcid":false,"given":"Meropi","family":"Karakioulaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine and Medical Center University Hospital Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100625.1996.tb00086.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.07.009"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1239"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1238"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18921"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2022.04.007"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0945\u2010053x(98)00007\u20109"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2025.02.001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.02.002"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.11.003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.144"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13945"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689719857657"},{"key":"e_1_2_10_15_1","first-page":"86","article-title":"Gene Therapy for a Lethal Genetic Blistering Disease: A Status Report","volume":"110","author":"Bauer E. 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