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To overcome these limitations, we propose a high\u2010efficiency in\u2010vesicle analysis strategy that integrates targeting probe delivery and regulation by protein signal amplification. By applying aptamer\u2010mediated membrane fusion and \u201clocked\u2010activated\u201d CRISPR\u2010Cas12a\u2010AcrVA1 (LACA) for protein signal regulation, we fabricated a yly12\u2010aptamer\u2010functionalized self\u2010assembled nanovesicle which encapsulate LACA\u2010system\u00a0(yly12\u2010lipo@Cas12a nanovesicle) as an in\u2010vesicle bioanalytical platform. Leveraging the high specificity of the aptamer and the regulatory function of AcrVA1 in selectively modulating Cas12a activity, the platform enables highly specifiec and sensitive detection, offering advantages of simple operation and versatility across platforms within only 2.5 h. Clinical analysis demonstrated effective differentiation between patients and healthy controls, yielding high diagnostic performance with an AUC of 0.965. The proposed platform shows great potential for EV\u2010carrying protein biomarker analysis and has broad prospects for the disease's diagnosis in clinical settings.<\/jats:p>","DOI":"10.1002\/anie.6795217","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:02:29Z","timestamp":1778166149000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti\u2010CRISPR Protein Regulates CRISPR\/Cas12a Fusogenic\u2010Nanovesicle\u2010Based Platform for Extracellular Vesicle\u2010Encapsulated Non\u2010Nucleic Acid Target In\u2010Vesicle Detection"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3310-192X","authenticated-orcid":false,"given":"Qiaoxuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine\/State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou 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