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Using adenosine deaminase acting on RNA (ADAR) effectors, A-I base conversions can be targeted using guide RNAs (gRNAs). We compare the Cas13 effectors PspCas13b and Cas13bt3 for the repair of the gene\n                    <jats:italic>USH2A<\/jats:italic>\n                    , a common cause of inherited retinal disease and Usher syndrome. In cultured cells, we demonstrate up to 80% efficiency for the repair of the common c.11864\u2009G\u2009&gt;\u2009A and its murine equivalent c.11840\u2009G\u2009&gt;\u2009A, across different gRNAs and promoters. We develop and characterize a mouse model of Usher syndrome carrying the c.11840\u2009G\u2009&gt;\u2009A mutation designed for the evaluation of base editors for inherited retinal disease. Finally, we compare Cas13 effectors delivered via AAV for the repair of\n                    <jats:italic>Ush2a<\/jats:italic>\n                    in photoreceptors. Mean RNA editing rates in photoreceptors across different constructs ranged from 0.32% to 2.04%, with greater efficiency in those injected with PspCas13b compared to Cas13bt3 constructs. In mice injected with PspCas13b constructs, usherin protein was successfully restored and correctly localized to the connecting cilium following RNA editing. These results support the development of transcriptome targeting gene editing therapies for retinal disease.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-07557-3","type":"journal-article","created":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T06:04:46Z","timestamp":1738994686000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comparison of CRISPR-Cas13b RNA base editing approaches for USH2A-associated inherited retinal degeneration"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0821-3954","authenticated-orcid":false,"given":"Lewis E.","family":"Fry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Major","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4300-2033","authenticated-orcid":false,"given":"Ahmed","family":"Salman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy A.","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4799-0465","authenticated-orcid":false,"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-7179","authenticated-orcid":false,"given":"Andrew J.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2941-4464","authenticated-orcid":false,"given":"Michelle E.","family":"McClements","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-4682","authenticated-orcid":false,"given":"Robert E.","family":"MacLaren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"7557_CR1","doi-asserted-by":"publisher","unstructured":"Kumar, S. et al. 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