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It is caused by mutations in\n                    <jats:italic>CYP4V2<\/jats:italic>\n                    gene, and about 80% of BCD patients carry mutations in exon 7 to 11. Here, we apply CRISPR\/Cas9 mediated homology-independent targeted integration (HITI)-based gene editing therapy in HEK293T cells, BCD patient derived iPSCs, and humanized\n                    <jats:italic>Cyp4v3<\/jats:italic>\n                    mouse model (\n                    <jats:italic>h-Cyp4v3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>mut\/mut<\/jats:italic>\n                    <\/jats:sup>\n                    ) using two rAAV2\/8 vectors via sub-retinal administration. We find that sgRNA-guided Cas9 generates double-strand cleavage on intron 6 of the\n                    <jats:italic>CYP4V2<\/jats:italic>\n                    gene, and the HITI donor inserts the carried sequence, part of intron 6, exon 7-11, and a stop codon into the DNA break, achieving precise integration, effective transcription and translation both in vitro and in vivo. HITI-based editing restores the viability of iPSC-RPE cells from BCD patient, improves the morphology, number and metabolism of RPE and photoreceptors in\n                    <jats:italic>h-Cyp4v3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>mut\/mut<\/jats:italic>\n                    <\/jats:sup>\n                    mice. These results suggest that HITI-based editing could be a promising therapeutic strategy for those BCD patients carrying mutations in exon 7 to 11, and one injection will achieve lifelong effectiveness.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-48092-9","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T03:02:54Z","timestamp":1714964574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["In vivo genome editing via CRISPR\/Cas9-mediated homology-independent targeted integration for Bietti crystalline corneoretinal dystrophy treatment"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-3254","authenticated-orcid":false,"given":"Xiang","family":"Meng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixuan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shicheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boling","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-228X","authenticated-orcid":false,"given":"Liping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"48092_CR1","first-page":"737","volume":"99","author":"G Bietti","year":"1937","unstructured":"Bietti, G. 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