{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:54:44Z","timestamp":1792418084576,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"58","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"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":["NSFC 32201059"],"award-info":[{"award-number":["NSFC 32201059"]}],"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"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    DNA\u2010binding proteins such as AP endonucleases are powerful scaffolds for biotechnology, but there is no general way to rewire their DNA\u2010contact surfaces. Here we report ARGENT (AI\u2010guided Arginine scanning Engine for Nucleic\u2010acid Tuning), an interpretable framework that uses protein\u2013DNA structures and homologous sequences to propose beneficial Arg substitutions and multi\u2010residue charge patches. Applied to the APE1\u2013DNA complex, ARGENT combines structural and evolutionary features into a residue\u2010wise hotspot score, compressing 276 candidate positions into 9 sites for testing. Six single mutants increase AP\u2010site cleavage, and the top\u2010ranked triple mutant, APE1\u2010Evo, connects three DNA\u2010contact patches, boosts the single\u2010turnover rate constant \u223c4\u2010fold relative to wild\u2010type APE1, and preserves mismatch discrimination at the AP\u2010opposite position. We embed APE1\u2010Evo into an upgraded NAPTUNE\u2010V2.0 architecture that couples AP\u2010site cleavage to a multilayer\n                    <jats:italic>Pf<\/jats:italic>\n                    Ago cascade, enabling multiplex detection of dengue virus pseudotypes and direct typing of influenza A and B viruses in clinical RNA with high concordance to qPCR. ARGENT also transfers to other DNA\u2010binding proteins, including\n                    <jats:italic>MG34\u20101<\/jats:italic>\n                    Cas9d, highlighting its broader relevance to genome\u2010editing enzymes. These results establish AI\u2010guided Arg scanning as a practical route to engineer hyperactive, high\u2010fidelity AP endonucleases and to tune DNA\u2010binding interfaces for next\u2010generation nucleic\u2010acid technologies and viral RNA sensing.\n                  <\/jats:p>","DOI":"10.1002\/advs.76769","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:19:03Z","timestamp":1784895543000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computation and Structure\u2010Guided Arginine Scanning Engineers a Hyperactive AP Endonuclease for Multiplex Viral RNA Sensing"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4849-1958","authenticated-orcid":false,"given":"Junlan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health Children's Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8292-7406","authenticated-orcid":false,"given":"Feizuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5514-7339","authenticated-orcid":false,"given":"Boyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for TCM\u2010X MOE Key Laboratory of Bioinformatics Bioinformatics Division BNRist Department of Automation Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6201-0920","authenticated-orcid":false,"given":"Xin Yu","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3978-4212","authenticated-orcid":false,"given":"Senfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-6171","authenticated-orcid":false,"given":"Shengsheng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0901-6354","authenticated-orcid":false,"given":"Yao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"},{"name":"International Joint Agriculture Research Center for Animal Bio\u2010Breeding of Ministry of Agriculture and Rural Affairs College of Animal Science and Technology Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9300-9040","authenticated-orcid":false,"given":"Fangyao","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-4762","authenticated-orcid":false,"given":"Zhifeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8276-4196","authenticated-orcid":false,"given":"Siyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0053-6967","authenticated-orcid":false,"given":"Kunming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8003-6698","authenticated-orcid":false,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health Children's Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1071-0239","authenticated-orcid":false,"given":"Yunxiang","family":"Zang","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1620-1344","authenticated-orcid":false,"given":"Xiaolong","family":"Wang","sequence":"additional","affiliation":[{"name":"International Joint Agriculture Research Center for Animal Bio\u2010Breeding of Ministry of Agriculture and Rural Affairs College of Animal Science and Technology Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-1247","authenticated-orcid":false,"given":"Xingxu","family":"Huang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8709-9167","authenticated-orcid":false,"given":"Shao","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for TCM\u2010X MOE Key Laboratory of Bioinformatics Bioinformatics Division BNRist Department of Automation Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanquan","family":"Ji","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-6515","authenticated-orcid":false,"given":"Tao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"},{"name":"National Clinical Research Center for Child Health Children's Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4509-4840","authenticated-orcid":false,"given":"Chunyi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Faculty of Science National University of Singapore  Singapore Singapore"},{"name":"Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Precision Medicine Translational Research Programme (TRP) Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1112"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0959\u2010437X(95)80006\u20109"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959\u2010440X(98)80009\u20102"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.12.002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add8643"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202410086"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2018.10.010"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2025.117968"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/D6SC00827E"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/138620706776843192"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.4c00887"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab673"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427\u2010023\u20102566\u20108"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114973"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01898-9"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.07.007"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202502593"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551\u2010023\u201001137\u20107"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959\u2010440X(96)80075\u20103"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10146"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq399"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad481"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh165"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201002175\u2010y"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3105"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.01.004"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202416631"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201056653\u20109"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-99-0113-5_1"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(14)60572\u20109"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13101967"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.8.2.14992"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2024.05.053"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010018\u20100115\u20101"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14171"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/v11080736"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/v15102032"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biophys\u2010062215\u2010010822"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060815-014607"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247997"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202401303"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3791\/1485"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjm\u20102020\u20100572"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2025.108196"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.849004"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0271"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.37201\/req\/159.2021"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57455-9"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55573-4"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035257\u20107"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62128-8"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594\u2010026\u201001761\u20103"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76769","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76769","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:14:13Z","timestamp":1792415653000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":52,"journal-issue":{"issue":"58","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/advs.76769"],"URL":"https:\/\/doi.org\/10.1002\/advs.76769","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"assertion":[{"value":"2026-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76769"}}