{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:17:34Z","timestamp":1790047054230,"version":"4.0.1"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN184073\u201018"],"award-info":[{"award-number":["RGPIN184073\u201018"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102020\u201006401"],"award-info":[{"award-number":["RGPIN\u20102020\u201006401"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["VR2\u2010172718"],"award-info":[{"award-number":["VR2\u2010172718"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ribonucleases are powerful degradative enzymes that rapidly cleave RNA and have long been regarded as obstacles to RNA diagnostics. Detecting large, structured RNA molecules in biological samples is further complicated by extensive secondary structures and abundant background RNA. Here we transform this destructive activity into a diagnostic advantage through a RNase I\u2013assisted rolling circle amplification (RI\u2010RCA) strategy that integrates enzymatic RNA digestion with circular DNA templates (CDTs) to achieve direct, reverse\u2010transcription\u2010free RNA detection. In this system,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    RNase I\u2014a widely available endoribonuclease\u2014selectively digests structured RNA to expose complementary CDT\u2010binding sites, which are immediately protected through duplex formation and converted into primers for RCA. The resulting reaction proceeds isothermally at room temperature in linear, quasi\u2010exponential, and exponential modes, achieving quantitative signal generation across concentrations from 50 aM to 50 fM and maintaining performance in 50% pooled human saliva. Applied to clinical saliva samples from SARS\u2010CoV\u20102\u2013positive and \u2013negative individuals, RI\u2010RCA achieved near\u2010perfect sensitivity and 98\u2013100% diagnostic accuracy. By coupling enzymatic RNA digestion with sequence\u2010specific protection via CDT hybridization, this strategy converts RNA instability from a liability into an analytical advantage, providing a simple, robust, and clinically translatable platform for accurate detection of structured RNA targets.\n                  <\/jats:p>","DOI":"10.1002\/anie.202525591","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:33:33Z","timestamp":1768808013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transforming RNA Degradation into Accurate RNA Detection: RNase I\u2013Assisted Rolling Circle Amplification for Clinical Samples"],"prefix":"10.1002","volume":"65","author":[{"given":"Amal","family":"Mathai","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"},{"name":"Biointerfaces Institute McMaster University  1280 Main Street West Hamilton Ontario L8S 4M1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"},{"name":"Biointerfaces Institute McMaster University  1280 Main Street West Hamilton Ontario L8S 4M1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3461-9824","authenticated-orcid":false,"given":"John D.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Biointerfaces Institute McMaster University  1280 Main Street West Hamilton Ontario L8S 4M1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"},{"name":"Biointerfaces Institute McMaster University  1280 Main Street West Hamilton Ontario L8S 4M1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0250169"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1840"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2619"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.04.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041588"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt284"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2020.103194"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2011.01.007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2021.1924059"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.23374"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2020.112356"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202014506"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c03822"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2021.113309"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002311"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.10"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2018.12.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.7.6.775"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.12.e63"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.57"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275\u2010015\u20104656\u20109"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3MB70304E"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2lc40100b"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00428"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/20.7.1691"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770701845204"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040204"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/b921140c"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2015.245829"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam9321"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b13960"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2021.113177"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.613304"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202300075"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010017\u20100632\u2010z"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr300362f"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2019.05.004"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00613H"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200705982"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3cs60439j"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph11020035"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2021.02.007"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2020.12.062"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201700054"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.10.019"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2018.03.065"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13206\u2010016\u20100402\u20106"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010137"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae778"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202507973"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378\u20101119(92)90072\u2010W"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170906"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2608.201246"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn5007418"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201006594\u20101"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CC00093J"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn1014"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201006642\u20105"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202525591","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202525591","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202525591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:39:38Z","timestamp":1774276778000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202525591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,18]]},"references-count":58,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,2,23]]}},"alternative-id":["10.1002\/anie.202525591"],"URL":"https:\/\/doi.org\/10.1002\/anie.202525591","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,18]]},"assertion":[{"value":"2025-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e25591"}}