{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:43:48Z","timestamp":1788936228417,"version":"build-2803163510"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19am0401022"],"award-info":[{"award-number":["JP19am0401022"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23bm1223009"],"award-info":[{"award-number":["JP23bm1223009"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109785"],"award-info":[{"award-number":["JP25ek0109785"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23bm1223011"],"award-info":[{"award-number":["JP23bm1223011"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The CRISPR\u2013Cas9 system has been widely adopted as a genome editing tool due to its high efficiency and versatility, contributing to the development of various therapeutic strategies. However, its clinical application remains limited by safety concerns, including off-target effects and large-scale chromosomal rearrangements such as translocations and inversions. Recently, the CRISPR\u2013Cas3 system, a Class 1 CRISPR effector complex with unidirectional DNA degradation activity, has gained attention as a potential alternative, offering reduced off-target activity. In this study, we applied the CRISPR\u2013Cas3 system to human T cells and successfully disrupted two clinically relevant genes, T cell receptor alpha constant (TRAC) and beta-2 microglobulin (B2M). These gene deletions were associated with a reduction in both graft-versus-host disease risk and host immune rejection. Importantly, no off-target mutations were detected in CRISPR\u2013Cas3-edited cells, in contrast to the off-target effects observed with CRISPR\u2013Cas9. Furthermore, CAR-T cells generated by deleting TRAC or B2M using CRISPR\u2013Cas3 maintained their antigen-specific cytotoxicity against tumor cells, while exhibiting reduced alloreactivity. These results suggest that CRISPR\u2013Cas3 provides a safer and promising platform for genome editing in T cell engineering, with potential applications in the development of next-generation allogeneic T cell therapies.<\/jats:p>","DOI":"10.1093\/narcan\/zcag009","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:49:56Z","timestamp":1774529396000},"source":"Crossref","is-referenced-by-count":1,"title":["Efficient gene disruption with CRISPR\u2013Cas3 in human T cells"],"prefix":"10.1093","volume":"8","author":[{"given":"Tomoaki","family":"Fujii","sequence":"first","affiliation":[{"name":"Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo , 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukimi","family":"Sakoda","sequence":"additional","affiliation":[{"name":"Department of Immunology, Yamaguchi University Graduate School of Medicine , 1-1-1 Minami-Kogushi, Ube 755-8505 ,","place":["Japan"]},{"name":"Research Institute for Cell Design Medical Science , 1-1-1 Minami-Kogushi, Ube 755-8505 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Yoshimi","sequence":"additional","affiliation":[{"name":"Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo , 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]},{"name":"Division of Genome Engineering, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo , 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Advanced Photon Technology Division, RIKEN SPring-8 Center , 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 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Animal Research Center, Institute of Medical Science, The University of Tokyo , 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]},{"name":"Division of Genome Engineering, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo , 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"2026050406164940100_B1","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1126\/science.1138140","article-title":"CRISPR provides acquired resistance against viruses in prokaryotes","volume":"315","author":"Barrangou","year":"2007","journal-title":"Science"},{"key":"2026050406164940100_B2","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial 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