{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:25:23Z","timestamp":1786976723142,"version":"build-2736575974"},"reference-count":97,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"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":["32070832"],"award-info":[{"award-number":["32070832"]}],"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":["32150610476"],"award-info":[{"award-number":["32150610476"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042022dx0003"],"award-info":[{"award-number":["2042022dx0003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    CRISPR\u2010Cas systems revolutionize gene regulation across diverse organisms, including zebrafish. However, most zebrafish studies still rely on transient delivery of CRISPR components, with limited use of transgenic models, primarily restricted to Cas9\u2010mediated knockouts. This limitation arises from challenges in achieving sustained, tissue\u2010specific, and efficient expression of transgenic CRISPR effectors. To address these challenges, we introduce CRISPR\u2010Q, a transgenic system that combines the QFvpr\/QUAS binary expression platform with CRISPR\u2010Cas technologies. CRISPR\u2010Q overcomes the drawbacks of transient mRNA or protein delivery and circumvents the toxicity and transgene silencing issues associated with other binary systems, such as Gal4\/UAS. The system enables robust and spatiotemporal expression of CasRx or dCas9vpr, allowing precise transcript knockdown (CRISPR\u2010Q\n                    <jats:sub>KD<\/jats:sub>\n                    ) or gene activation (CRISPR\u2010Qa). Using CRISPR\u2010Q\n                    <jats:sub>KD<\/jats:sub>\n                    , we achieve effective knockdown of\n                    <jats:italic>smn1<\/jats:italic>\n                    and simultaneous knockdown of\n                    <jats:italic>tardbp<\/jats:italic>\n                    and\n                    <jats:italic>tardbpl<\/jats:italic>\n                    , modeling spinal muscular atrophy and amyotrophic lateral sclerosis, respectively. CRISPR\u2010Qa activates endogenous\n                    <jats:italic>lin28a<\/jats:italic>\n                    and\n                    <jats:italic>sox9b<\/jats:italic>\n                    , demonstrating its functional versatility. We further validate CRISPR\u2010Q's tissue\u2010specific applicability in heart\u2010specific transgenic zebrafish. Together, CRISPR\u2010Q represents a robust and versatile platform for studying gene function and modeling human diseases in zebrafish, with broad potential for adaptation in other model organisms.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511485","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:18:34Z","timestamp":1770837514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Versatile CRISPR\u2010Cas Tools for Gene Regulation in Zebrafish via an Enhanced Q Binary System"],"prefix":"10.1002","volume":"13","author":[{"given":"Miaoyuan","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqi","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocatalysis and Enzyme Engineeringhubei Hongshan Laboratory, School of Life Sciences Hubei University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocatalysis and Enzyme Engineeringhubei Hongshan Laboratory, School of Life Sciences Hubei University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-0166","authenticated-orcid":false,"given":"Yanxun V.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2632-3237","authenticated-orcid":false,"given":"Youngnam N.","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2501"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.161638.113"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1308335110"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3360"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.06.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi8870"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-018-0050-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.029"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.122"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.022"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.35"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.777094"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24049"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaq0180"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.033"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/v10120732"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky433"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.07.013"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.115.176917"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.01.032"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2016.10.005"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg4243"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.01.002"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-018-09591-0"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.100057"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903060106"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3250"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.025"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1929"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2013.06.012"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460\u20102075.1992.tb05603.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3871"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/crispr.2021.0013"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac582"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010017\u20100060\u20106"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2020.07.007"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010021\u201002923\u20103"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.12.023"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010021\u201001124\u20104"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14580"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101064\u2010z"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101057\u2010y"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201057792\u20109"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02860-w"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.06.005"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115551"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13100\u2010016\u20100062\u2010z"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(95)90460\u20103"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(80)90847\u20108"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1637\u201006.2006"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt110"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/170494b0"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2009.04.066"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.094"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2089"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011936\u2010w"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301489"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.166587"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr901076y"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.02.028"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00117"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010023\u201000846\u20107"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.00026"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010010\u20100659\u20100"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218311110"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00331-z"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2022.102284"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.02.050"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010022\u201000742\u20102"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00039.2017"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.04.008"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.03.004"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.050351"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-111523-101949"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.902941"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.320396"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn073"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00838"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201067201\u20108"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu186"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/jdb7030015"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088086"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010022\u201001419\u20107"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.08.001"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010020\u20100456\u20109"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201015526\u20107"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.95"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166020"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201031476\u20105"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201046412\u20107"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2022.03.006"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010018\u20100098\u20100"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv035"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224243"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010020\u20100376\u20107"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.165753"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100709"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511485","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202511485","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511485","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:26:13Z","timestamp":1776939973000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202511485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":97,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/advs.202511485"],"URL":"https:\/\/doi.org\/10.1002\/advs.202511485","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"assertion":[{"value":"2025-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e11485"}}