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Here, we describe a strategy to enhance or induce SCR in a transcript-selective manner using a CRISPR-dCas13 system. Using specific guide RNAs, we target dCas13 to the region downstream of canonical stop codons of mammalian\n                    <jats:italic>AGO1<\/jats:italic>\n                    and\n                    <jats:italic>VEGFA<\/jats:italic>\n                    mRNAs, known to exhibit natural SCR. Readthrough assays reveal enhanced SCR of these mRNAs (both exogenous and endogenous) caused by the dCas13-gRNA complexes. This effect is associated with ribosomal pausing, which has been reported for several SCR events. Our data show that CRISPR-dCas13 can also induce SCR across premature termination codons (PTCs) in the mRNAs of green fluorescent protein and TP53. We demonstrate the utility of this strategy in the induction of readthrough across the thalassemia-causing PTC in\n                    <jats:italic>HBB<\/jats:italic>\n                    mRNA and hereditary spherocytosis-causing PTC in\n                    <jats:italic>SPTA1<\/jats:italic>\n                    mRNA. Thus, CRISPR-dCas13 can be programmed to enhance or induce SCR in a transcript-selective and stop codon-specific manner.\n                  <\/jats:p>","DOI":"10.1038\/s44319-024-00115-8","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T12:02:17Z","timestamp":1710763337000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transcript-specific induction of stop codon readthrough using a CRISPR-dCas13 system"],"prefix":"10.1038","volume":"25","author":[{"given":"Lekha E","family":"Manjunath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3735-561X","authenticated-orcid":false,"given":"Anumeha","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Devi Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirtana","family":"Vasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debaleena","family":"Kar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthi","family":"Sellamuthu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7903-5198","authenticated-orcid":false,"given":"Sandeep M","family":"Eswarappa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"115_CR1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/nature24049","volume":"550","author":"OO Abudayyeh","year":"2017","unstructured":"Abudayyeh OO, Gootenberg JS, Essletzbichler P, Han S, Joung J, Belanto JJ, Verdine V, Cox DBT, Kellner MJ, Regev A et al (2017) RNA targeting with CRISPR-Cas13. 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The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}],"article-number":"26"}}