{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:47:03Z","timestamp":1792036023338,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371521"],"award-info":[{"award-number":["32371521"]}],"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":["62231025"],"award-info":[{"award-number":["62231025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Detection of gene mutations related to acute myeloid leukemia (AML) is crucial for its early diagnosis, personalized treatment, and recurrence monitoring. However, accurate detection of diverse mutations occurring at the same locus remains technically challenging. The CRISPR\/Cas system, with its unique programmable nucleic acid recognition capabilities, provides a promising solution. Here, we elucidated that CRISPR\/LwaCas13a is tolerant to consecutive substitutions but highly sensitive to insertions or deletions (indels) at specific positions of the spacer sequence, enabling rational CRISPR RNA (crRNA) design for multiplex detection of same\u2010site indels. Guided by these principles, we achieved effective detection of ultra\u2010multiplex\u00a0\n                    <jats:italic>nucleophosmin 1<\/jats:italic>\n                    (\n                    <jats:italic>NPM1<\/jats:italic>\n                    ) c.863_864 4\u2010bp insertions with a single crRNA, while maintaining specificity against the wild\u2010type transcripts. We further established a one\u2010pot CRISPR system, CRISPR\u2010Scan, by integrating recombinase polymerase amplification with LwaCas13a cleavage. CRISPR\u2010Scan enabled detection of mutations in backgrounds as low as 0.01%. In clinical validation, it identified\n                    <jats:italic>NPM1<\/jats:italic>\n                    mutations in 43 of 120 AML patients, consistent with next\u2010generation sequencing (NGS). Continuous monitoring of four AML patients indicated early recurrence with higher sensitivity than first\u2010generation sequencing (FGS) and full concordance with NGS. A microfluidic chip and portable device further facilitate accurate AML mutation detection. This platform offers an efficient and convenient approach for early AML diagnosis and measurable residual disease (MRD) monitoring.\n                  <\/jats:p>","DOI":"10.1002\/advs.78229","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:14:22Z","timestamp":1792034062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CRISPR\u2010Scan: Cas13a Mismatch Tolerance Enabled Ultra\u2010Multiplexed Detection of Same\u2010Site Indels in Acute Myeloid Leukemia"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8497-4753","authenticated-orcid":false,"given":"Linlin","family":"Bai","sequence":"first","affiliation":[{"name":"Center for Medical Research and Innovation Department of Laboratory Medicine Shanghai Pudong Hospital Human Phenome Institute State Key Laboratory of Genetics and Development of Complex Phenotypes School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery School of Medicine Advanced Institute for Life and Health Zhongda Hospital Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingmin","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Medical Research and Innovation Department of Laboratory Medicine Shanghai Pudong Hospital Human Phenome Institute State Key Laboratory of Genetics and Development of Complex Phenotypes School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Medical Research and Innovation Department of Laboratory Medicine Shanghai Pudong Hospital Human Phenome Institute State Key Laboratory of Genetics and Development of Complex Phenotypes School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Ji","sequence":"additional","affiliation":[{"name":"Center for Medical Research and Innovation Department of Laboratory Medicine Shanghai Pudong Hospital Human Phenome Institute State Key Laboratory of Genetics and Development of Complex Phenotypes School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology Peking University Shenzhen Hospital Shenzhen Peking University\u2010The Hong Kong University of Science and Technology Medical Center  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3237-1522","authenticated-orcid":false,"given":"Ziwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai Institute of Pancreatic Diseases National Key Laboratory of Immunity and Inflammation Changhai Hospital Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7408-016X","authenticated-orcid":false,"given":"Kaiming","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Medical Research and Innovation Department of Laboratory Medicine Shanghai Pudong Hospital Human Phenome Institute State Key Laboratory of Genetics and Development of Complex Phenotypes School of Life Sciences Fudan University Shanghai 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biological Science and Engineering Fuzhou University  Fuzhou China"},{"name":"Research Institute for Microbiology and Department of Food Science and Nutrition The Hong Kong Polytechnic University  Kowloon Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8269-5296","authenticated-orcid":false,"given":"Yongming","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Medical Research and Innovation Department of Laboratory Medicine Shanghai Pudong Hospital Human Phenome Institute State Key Laboratory of Genetics and Development of Complex Phenotypes School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongju","family":"Mao","sequence":"additional","affiliation":[{"name":"Center for Medical 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