{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:17:29Z","timestamp":1788157049620,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Schmidt Science Fellowship"},{"name":"Rhodes Trust"},{"name":"Burroughs Wellcome Career Award"},{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI-1548297"],"award-info":[{"award-number":["DBI-1548297"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wagner Foundation"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["4R33AI140465-04"],"award-info":[{"award-number":["4R33AI140465-04"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010296","name":"James B. Pendleton Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010296","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000936","name":"Gordon and Betty Moore Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000936","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CRISPR diagnostics enable sensitive detection of infectious diseases, with the RNA endonuclease Cas13a providing specific, amplification-free RNA detection through collateral trans-cleavage of fluorescent reporters. However, background cleavage from unbound enzyme, contaminating nucleases, and unsynchronized initiation of reactions limits assay sensitivity and interpretability. A strategy to precisely control the onset of Cas13a catalytic activity, essentially a molecular \u201cstarting gun,\u201d would address these challenges. Here, we introduce Light-Uncaged Cas13a (LUCas), a light-controllable system that directly blocks Cas13a trans-cleavage activity using a photocleavable interfering guide RNA, even in the presence of target RNA. Brief UV illumination releases this suppression, restoring full activity. Quantitative kinetic analysis reveals an ~100-fold suppression of trans-cleavage activity prior to photo-uncaging, including suppression of target-independent background activity. Using measured kinetic parameters, we predict and experimentally validate the limit of detection of the LUCas system for direct detection. We further demonstrate a multiplexed detection strategy termed \u201ctemporal barcoding,\u201d enabling quantitative detection of viral co-infections in a single bulk reaction. Finally, LUCas is shown to be compatible with one-pot isothermal amplification for enhanced sensitivity and direct detection of target RNA spiked into blood plasma. Together, these results establish LUCas as a general framework for mechanistically informed, light-based control of Cas13a activity.<\/jats:p>","DOI":"10.1093\/nar\/gkag848","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:15:09Z","timestamp":1786965309000},"source":"Crossref","is-referenced-by-count":0,"title":["LUCas: Light-Uncaged Cas13a using photocleavable interfering guide RNAs"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-6482","authenticated-orcid":false,"given":"Carlos F","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of California , Berkeley, CA 94720 ,","place":["United States"]},{"name":"UC Berkeley-UC San Francisco Graduate Program in Bioengineering, University of California , Berkeley, CA 94720 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4504-1530","authenticated-orcid":false,"given":"Deepak","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California , Berkeley, CA 94720 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8292-2816","authenticated-orcid":false,"given":"Andres","family":"Dextre","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California , Berkeley, CA 94720 ,","place":["United States"]},{"name":"UC Berkeley-UC San Francisco Graduate Program in Bioengineering, University of California , Berkeley, CA 94720 ,","place":["United 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