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Here we show that the clustered regularly interspaced short palindromic repeats (CRISPR)-Csm complex, a multiprotein effector from type III CRISPR immune systems in prokaryotes, provides surgical RNA ablation of both nuclear and cytoplasmic transcripts. As part of the most widely occurring CRISPR adaptive immune pathway, CRISPR-Csm uses a programmable RNA-guided mechanism to find and degrade target RNA molecules without inducing indiscriminate\n                    <jats:italic>trans<\/jats:italic>\n                    -cleavage of cellular RNAs, giving it an important advantage over the CRISPR-Cas13 family of enzymes. Using single-vector delivery of the\n                    <jats:italic>Streptococcus thermophilus<\/jats:italic>\n                    Csm complex, we observe high-efficiency RNA knockdown (90\u201399%) and minimal off-target effects in human cells, outperforming existing technologies including short hairpin RNA- and Cas13-mediated knockdown. We also find that catalytically inactivated Csm achieves specific and durable RNA binding, a property we harness for live-cell RNA imaging. These results establish the feasibility and efficacy of multiprotein CRISPR-Cas effector complexes as RNA-targeting tools in eukaryotes.\n                  <\/jats:p>","DOI":"10.1038\/s41587-022-01649-9","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T12:02:44Z","timestamp":1674475364000},"page":"1256-1264","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Precise transcript targeting by CRISPR-Csm complexes"],"prefix":"10.1038","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6995-7079","authenticated-orcid":false,"given":"David","family":"Colognori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marena","family":"Trinidad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9161-999X","authenticated-orcid":false,"given":"Jennifer A.","family":"Doudna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"1649_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1146\/annurev-biophys-083012-130404","volume":"42","author":"RC Wilson","year":"2013","unstructured":"Wilson, R. 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J.A.D. is a cofounder of Caribou Biosciences, Editas Medicine, Intellia Therapeutics and Mammoth Biosciences, and a director of Johnson & Johnson, Altos Labs and Tempus. J.A.D. is a scientific advisor to Caribou Biosciences, Intellia Therapeutics, Mammoth Biosciences, Scribe Therapeutics, Algen, Felix and Inari; J.A.D. serves on the scientific advisory boards of Sixth Street and The Column Group. J.A.D. has research projects sponsored by Roche and Apple Tree Partners. The other author declares no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}