{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:40:17Z","timestamp":1787946017669,"version":"build-2784847793"},"reference-count":37,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>\n                    Mutations leading to premature termination codons in\n                    <jats:italic toggle=\"yes\">COL7A1<\/jats:italic>\n                    are commonly associated with severe generalized recessive dystrophic epidermolysis bullosa (RDEB). Previous research, including our own, has indicated that removing mutated\n                    <jats:italic toggle=\"yes\">COL7A1<\/jats:italic>\n                    exons along with the consequent reframing of\n                    <jats:italic toggle=\"yes\">COL7A1<\/jats:italic>\n                    may not pose noticeable impact on protein function, offering a potential therapeutic strategy. However, investigations into the long-term\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    effects of genome editing-mediated removal of mutant exons have only focused on the small exon 80 thus far. Hence, this study focuses on exons 73 and 105 of\n                    <jats:italic toggle=\"yes\">COL7A1<\/jats:italic>\n                    to explore whether targeted exon removal, through a CRISPR\/Cas9-assisted, Non-homologous end joining (NHEJ)-mediated approach, could be extended to other larger exons. Introducing ribonucleoprotein complexes carrying Cas9 and optimized sgRNA guide pairs for each exon (73 and 105) through electroporation efficiently led to their removal, consequently restoring type VII collagen (C7) synthesis in RDEB primary patient cells carrying frameshift mutations in these exons.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    tests indicated the normal stability of the resulting C7 variants expressed at physiological levels, while\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    analyses of regenerated skin grafted onto immunodeficient mice using E73 or E105 RDEB edited cells demonstrated the proper deposition of C7 at the basement membrane zone, thereby restoring normal dermo-epidermal adherence. This study enhances the broader potential of the exon deletion approach in the treatment of RDEB.\n                  <\/jats:p>","DOI":"10.1089\/hum.2024.238","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T04:30:01Z","timestamp":1748406601000},"page":"1211-1221","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Safe and Efficacious Permanent Removal of Large COL7A1 Exons for Gene Reframing as a Reliable Therapeutic Strategy for Recessive Dystrophic Epidermolysis Bullosa"],"prefix":"10.1177","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0346-9192","authenticated-orcid":false,"given":"Sergio","family":"L\u00f3pez-Manzaneda","sequence":"first","affiliation":[{"name":"Department of Biomedical Innovation CIEMAT-CIBERER, Madrid, Spain"},{"name":"Instituto de Investigacion Sanitaria. 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Fundaci\u00f3n Jimenez D\u00edaz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3413-692X","authenticated-orcid":false,"given":"Alex","family":"Bassons-Bascu\u00f1ana","sequence":"additional","affiliation":[{"name":"Instituto de Investigacion Sanitaria. Fundaci\u00f3n Jimenez D\u00edaz, Madrid, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Raras (CIBERER), Valencia, Spain"},{"name":"Department of Bioengineering, University Carlos III Madrid (UC3M), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8598-8537","authenticated-orcid":false,"given":"Marta","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Investigacion Sanitaria. Fundaci\u00f3n Jimenez D\u00edaz, Madrid, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Raras (CIBERER), Valencia, Spain"},{"name":"Department of Bioengineering, University Carlos III Madrid (UC3M), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-2240","authenticated-orcid":false,"given":"Alexander","family":"Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Center\u2014University Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-5348","authenticated-orcid":false,"given":"Blanca","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Biomedical Innovation CIEMAT-CIBERER, Madrid, Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Raras (CIBERER), Valencia, Spain"},{"name":"Department of Bioengineering, University Carlos III Madrid (UC3M), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-1389","authenticated-orcid":false,"given":"Sara","family":"Llames","sequence":"additional","affiliation":[{"name":"Instituto de Investigacion Sanitaria. 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