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Current treatment options, such as allogeneic hematopoietic stem cell transplantation (aHSCT), are associated with significant risks, highlighting the need for alternative therapeutic strategies. In this study, we report the first a proof-of-concept CRISPR-Cas9\u2013mediated correction of a hypomorphic\n                    <jats:italic>DCLRE1C<\/jats:italic>\n                    variant (c.194\u00a0C\u2009&gt;\u2009T; p.T65I) in CD4\u2009+\u2009helper T (Th) cells using CRISPR-Cas9 gene-editing technology. CD4\u2009+\u2009Th cells were isolated, and the variant region was edited with sgRNA and donor DNA. Gene editing efficiency was confirmed by Sanger sequencing, revealing successful restoration of the target region to its wild-type sequence. Functional analyses showed a significant increase in CD25 activation and Artemis protein expression post-editing, although\n                    <jats:italic>DCLRE1C<\/jats:italic>\n                    mRNA levels remained unchanged. The approximately 6\u20138% increase in CD25 expression was statistically significant but did not reach healthy control levels. These findings suggest that CRISPR-Cas9 \u2013mediated gene editing may enable precise correction and induce measurable cellular-level functional changes, supporting biological feasibility rather than therapeutic efficacy. This study provides a foundation for future research on HSCs and underscores the potential role of CRISPR-Cas9\u2013based approaches in the treatment of inborn errors of immunity (IEIs) associated with\n                    <jats:italic>DCLRE1C<\/jats:italic>\n                    variants.\n                  <\/jats:p>","DOI":"10.1007\/s12026-026-09758-2","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T15:26:57Z","timestamp":1772292417000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CRISPR-Cas9\u2013based gene editing as a proof-of-concept approach in an inborn error of immunity caused by a DCLRE1C variant"],"prefix":"10.1007","volume":"74","author":[{"given":"Tugce","family":"Duran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Ali","family":"Karaselek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak","family":"Dagdelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkan","family":"Kuccukturk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00fckr\u00fc Nail","family":"Guner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevgi","family":"Keles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Reisli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"issue":"3","key":"9758_CR1","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/S0022-3476(97)70199-9","volume":"130","author":"RH Buckley","year":"1997","unstructured":"Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, Roberts JL, Puck JM. 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Zool Res. 2025;46(1):249\u201360.","journal-title":"Zool Res"}],"container-title":["Immunologic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-026-09758-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12026-026-09758-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-026-09758-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:06:21Z","timestamp":1781636781000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12026-026-09758-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9758"],"URL":"https:\/\/doi.org\/10.1007\/s12026-026-09758-2","relation":{},"ISSN":["1559-0755"],"issn-type":[{"value":"1559-0755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,28]]},"assertion":[{"value":"20 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The studies reported herein were approved by Necmettin Erbakan University Scientific Research Ethics Committee (Approval date and number: 05.07.2024, 2024\/5066). Informed consent was obtained from all patients in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20"}}