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Here, we propose an autocatalytic rolling circle amplification (A\u2010RCA) system for the precise identification of RV genomic markers through sequence\u2010specific target recognition and synergistic catalytic signal amplification. The system, which we incorporated into lateral\u2010flow strip tests, exploits the cross\u2010stimulation between deoxyribonuclease (DNAzyme) self\u2010cleavage reaction and rolling circle amplification (RCA) to exponentially amplify the recognition of virus RNA sequences for the visually perceptible signal transduction. With superior amplification efficiency, this innovative autocatalysis\u2010driven artificial reaction system facilitates the rapid and robust detection of various viral RNAs, including those of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS\u2010CoV\u20102), influenza A, and influenza B, with single\u2010nucleotide resolution, offering a portable diagnostic platform for unsupervised self\u2010examination of different RVs and their mutants. This modular A\u2010RCA system is adaptable for multiplexed viral RNA profiling in clinical nasopharyngeal swabs and implemented on lateral\u2010flow strip assays for point\u2010of\u2010care (POC) diagnostics. The accessibility and programmability of the A\u2010RCA system make it a promising candidate for epidemiological surveillance in resource\u2010limited settings, facilitating the prompt response to emerging RVs and the prevention of viral pandemics.<\/jats:p>","DOI":"10.1002\/anie.202518925","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T10:38:05Z","timestamp":1763635085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Point\u2010of\u2010Care Diagnosis of Respiratory Viruses at Single\u2010Nucleotide Resolution with an Autocatalytic Rolling Circle Amplification System"],"prefix":"10.1002","volume":"64","author":[{"given":"Jinhua","family":"Shang","sequence":"first","affiliation":[{"name":"College of Chemistry and Molecular Sciences Department of Clinical Laboratory Center for Gene Diagnosis and Program of Clinical Laboratory Zhongnan Hospital of Wuhan University Wuhan University  Wuhan 430072 P. 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