{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:14:17Z","timestamp":1791684857271,"version":"4.3.4"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271512"],"award-info":[{"award-number":["32271512"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572281"],"award-info":[{"award-number":["82572281"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Basic Research Program of Shaanxi","award":["2022JC-56"],"award-info":[{"award-number":["2022JC-56"]}]},{"name":"Natural Science Basic Research Program of Shaanxi","award":["2023-JC-ZD-43"],"award-info":[{"award-number":["2023-JC-ZD-43"]}]},{"name":"Natural Science Basic Research Program of Shaanxi","award":["2024JC-YBQN-0168"],"award-info":[{"award-number":["2024JC-YBQN-0168"]}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2023A1515110886"],"award-info":[{"award-number":["2023A1515110886"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The CRISPR\/Cas9 system is a powerful genome editing tool that has the potential to be applied to a variety of biomedical applications. Despite the considerable potential of this gene editing technology, there are numerous safety concerns including the possibility of unpredictable off-target effects. The splicing process, which involves the removal of introns from pre-mRNA and the alignment of exons to produce mature transcripts, is a critical step in gene expression in most eukaryotes. In this study, we present a spliceosome-responsive CRISPR\/Cas9 (SpC) editor that utilizes the splicing inhibitor pladienolide B (PB) to regulate pre-mRNA splicing and control the expression of the anti-CRISPR protein AcrIIA4, thereby modulating the activity of the Cas9 nuclease. This approach allows for precise regulation of the gene editing process, thereby effectively mitigating off-target effects. The reliability and robustness of the SpC editor were demonstrated through in vitro and in vivo bioluminescence imaging. Furthermore, a dual-target sgRNA was designed to target the diphtheria toxin A gene, resulting in apoptosis induction and growth inhibition of tumor cells across various types of cancer cells. Our results indicate that this SpC editor has the capacity to precisely regulate tumor cell growth, thus providing new insights and significant implications for cancer gene therapy.<\/jats:p>","DOI":"10.1093\/nar\/gkaf1328","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:11:04Z","timestamp":1762521064000},"source":"Crossref","is-referenced-by-count":3,"title":["An SpC editor targeting pre-mRNA splicing for precise CRISPR control and enhanced antitumor efficacy"],"prefix":"10.1093","volume":"53","author":[{"given":"Xiaorui","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, The Second Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi 710004 ,","place":["China"]},{"name":"Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University , Xi\u2019an 710071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Hu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University , Xi\u2019an 710071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Second Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi 710004 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Lei","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Molecular and Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University , Xi\u2019an 710071 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