{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:31:15Z","timestamp":1790875875328,"version":"4.1.0"},"reference-count":52,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"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":["The CRISPR Journal"],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:p>\n                    Safety considerations for gene therapies of inherited preleukemia syndromes, including severe congenital neutropenia (CN), are paramount. We compared several strategies for CRISPR\/Cas9 gene editing of autosomal-dominant\n                    <jats:italic toggle=\"yes\">ELANE<\/jats:italic>\n                    mutations in CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells from two CN patients head-to-head. We tested universal and allele-specific\n                    <jats:italic toggle=\"yes\">ELANE<\/jats:italic>\n                    knockout,\n                    <jats:italic toggle=\"yes\">ELANE<\/jats:italic>\n                    mutation correction by homology-directed repair (HDR) with AAV6, and allele-specific HDR with ssODN. All strategies were not toxic, had at least 30% editing, and rescued granulopoiesis\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . In contrast to published data, allele-specific indels in the last exon of\n                    <jats:italic toggle=\"yes\">ELANE<\/jats:italic>\n                    also restored granulopoiesis. Moreover, by implementing patient-derived induced pluripotent stem cells for GUIDE-Seq off-target analysis, we established a clinically relevant \u201cpersonalized\u201d assessment of off-target activity of gene editing on the background of the patient\u2019s genome. We found that allele-specific approaches had the most favorable off-target profiles. Taken together, a well-defined head-to-head comparison pipeline for selecting the appropriate gene therapy is essential for diseases with several gene editing strategies available.\n                  <\/jats:p>","DOI":"10.1089\/crispr.2024.0006","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T10:00:21Z","timestamp":1729591221000},"page":"258-271","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Comparison of Gene-Editing Approaches for Severe Congenital Neutropenia-Causing Mutations in the\n                    <i>ELANE<\/i>\n                    Gene"],"prefix":"10.1177","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-7564","authenticated-orcid":false,"given":"Malte Ulrich","family":"Ritter","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Nasri","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Dannenmann","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perihan","family":"Mir","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Secker","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Amend","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maksim","family":"Klimiankou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Welte","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4399-2324","authenticated-orcid":false,"given":"Julia","family":"Skokowa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."},{"name":"Gene and RNA Therapy Center, T\u00fcbingen University, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01915-4"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-538025"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.32"},{"issue":"16","key":"e_1_3_6_5_2","first-page":"1885","article-title":"Stem cell transplantation in severe congenital neutropenia: An analysis from the European Society for Blood and Marrow Transplantation","volume":"126","author":"Fioredda F","year":"2015","unstructured":"Fioredda F, , Iacobelli S, , Van Biezen A, et al. Severe Aplastic Anemia the Inborn Error, and the Pediatric Disease Working Parties of the European Society for Blood and Bone Marrow Transplantation (EBMT) and Stem Cell Transplant for Immunodeficiencies in Europe (SCETIDE). Stem cell transplantation in severe congenital neutropenia: An analysis from the European Society for Blood and Marrow Transplantation. 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