{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T23:31:53Z","timestamp":1769383913837,"version":"3.49.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Mucopolysaccharidosis type I (MPS I) is caused by alpha-L-iduronidase deficiency encoded by the<jats:italic>IDUA<\/jats:italic>gene. Therapy with CRISPR\/Cas9 is being developed for treatment, however a detailed investigation of off-target effects must be performed. This study aims to evaluate possible off-targets for a sgRNA aiming to correct the most common variant found in MPS I patients (p.Trp402*). A total of 272 potential off-target sequences was obtained and 84 polymorphic sites were identified in these sequences with a frequency equal to or greater than 1% in at least one of the populations. In the majority of cases, polymorphic sites decrease the chance of off-target cleavage and a new PAM was created, which indicates the importance of such analysis. This study highlights the importance of screening off-targets in a population-specific context using Mucopolysaccharidosis type I as an example of a problem that concerns all therapeutic treatments. Our results can have broader applications for other targets already clinically in use, as they could affect CRISPR\/Cas9 safety and efficiency.<\/jats:p>","DOI":"10.1371\/journal.pone.0262299","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T18:33:21Z","timestamp":1643049201000},"page":"e0262299","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["In silico analysis of potential off-target sites to gene editing for Mucopolysaccharidosis type I using the CRISPR\/Cas9 system: Implications for population-specific treatments"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8401-3332","authenticated-orcid":true,"given":"Paola","family":"Carneiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4178-6604","authenticated-orcid":true,"given":"Martiela Vaz","family":"de Freitas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ursula","family":"Matte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"pone.0262299.ref001","first-page":"3421","article-title":"Muenzer J The mucopolysaccharidosis","author":"E.F. 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