{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:40:32Z","timestamp":1792406432010,"version":"4.4.0"},"reference-count":161,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      CRISPR\u2010Cas9 gene editing has transformed molecular biology and has great potential as a therapeutic tool for cancer and many other human diseases. This perspective review elaborates on the recent advances in CRISPR\u2010Cas9 technology and its application as an innovative cancer treatment. Additionally, this perspective outlines the current barriers to clinical translation, including\n                      <jats:italic>in vivo<\/jats:italic>\n                      delivery and off\u2010target effects, as well as potential mitigation strategies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>CRISPR\u2010Cas9 has enabled the development of innovative methods to enhance immunotherapy, overcome drug resistance, and identify new therapeutic targets. Importantly, CRISPR\u2010Cas9\u2010induced DNA double\u2010strand breaks can activate p53\u2010mediated selection and cause unintended on\u2010target genomic alterations, including large deletions, chromosomal rearrangements, and chromosome loss. While progress has been made toward addressing these significant obstacles, optimizing delivery systems, minimizing off\u2010target effects, and addressing immunogenicity are critical for the successful clinical application of CRISPR\u2010Cas9. Emerging strategies, including high\u2010fidelity Cas9 variants, optimized guide RNAs, and advanced non\u2010viral delivery systems such as lipid nanoparticles (LNPs) and exosomes, may improve the precision, safety, and delivery of CRISPR\u2010Cas9\u2010based therapies. Continued innovation in base editing and prime editing may enable the development of more refined approaches for precise genome modification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>From a translational perspective, we argue that improvements in editing efficiency alone will be insufficient; clinical success will require the simultaneous achievement of tumor\u2010selective delivery, genomic integrity, and acceptable long\u2010term safety. Therefore, the continued development of novel approaches should be promoted to realize the full potential of CRISPR\u2010Cas9 technology in oncology and other therapeutic applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.73308","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:35:02Z","timestamp":1790321702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CRISPR\u2010Cas9 in Cancer Therapy: Overcoming Delivery Barriers and Off\u2010Target Effects for Clinical Translation"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7313-8655","authenticated-orcid":false,"given":"Md","family":"Mohiuddin","sequence":"first","affiliation":[{"name":"Department of Pharmacy Southeast University Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0955-6934","authenticated-orcid":false,"given":"Md Al Mamun","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Department of Public Health Daffodil International University Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1258096"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091014-104441"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1159689"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138140"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-3695"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040806"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.7b00057"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2015.069"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/v11010028"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.112724"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-024-00561-1"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crbiot.2026.100382"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba7365"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21405"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02444-y"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6031769"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-24-592"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.54097\/hset.v45i.7397"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0005-8"},{"issue":"9","key":"e_1_2_16_22_1","first-page":"3986","article-title":"Targeting 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