{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:34Z","timestamp":1787029234314,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordination for the Imauto-comprovement of Higher Education Personnel\u2014Brazil (CAPES)","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Oswaldo Cruz Institute","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"National Council for Scientific and Technological Development (CNPq)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"The Foundation for Scientific and Technological Development in Health (FIOTEC)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Herpes simplex virus-1 (HSV-1) can invade the central nervous system (CNS). However, antiviral drugs used to treat HSV-1 have significant toxicity and resistance. An alternative approach involves the use of the CRISPR\/Cas9 complex as a viral replication inhibitor. Editing the UL39 gene with CRISPR\/Cas9 results in &gt;95% inhibition of HSV-1 replication in vitro; however, few studies have investigated alternative therapies in in vivo models. This study aimed to investigate the efficacy of CRISPR\/Cas9 targeting the UL39 region, which was administered via the ocular route, to reduce the HSV-1 viral count in the CNS of BALB\/c mice. Mice were inoculated with HSV-1 and treated using CRISPR\/Cas9. The kinetics of CNS infection were assessed, and the effects of CRISPR\/Cas9 were compared with those of topical acyclovir treatments. The brain viral load was analyzed, and histopathology and immunofluorescence of the nervous tissue were performed. The group treated with CRISPR\/Cas9 showed a reduced viral load on the seventh day post-infection, and no brain inflammation or chromatin compaction was observed in animals that received CRISPR\/Cas9 therapy. These findings suggest that CRISPR\/Cas9 anti-UL39 therapy can reduce the HSV-1 viral load in brain tissue. Therefore, investigating viral detection and evaluating antiviral treatments in the brain is essential.<\/jats:p>","DOI":"10.3390\/pathogens13121087","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T04:15:03Z","timestamp":1733804103000},"page":"1087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CRISPR\/Cas9 Eye Drop HSV-1 Treatment Reduces Brain Viral Load: A Novel Application to Prevent Neuronal Damage"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2334-0289","authenticated-orcid":false,"given":"Rafaela Moraes Pereira","family":"de Sousa","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Virologia e Parasitologia Molecular, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Silveira","family":"Garcia","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia e Parasitologia Molecular, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-8373","authenticated-orcid":false,"given":"Felipe Sim\u00f5es","family":"Lemos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040-361, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5969-9109","authenticated-orcid":false,"given":"Viviane Souza","family":"de Campos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Machado Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hepatites Virais, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3349-6183","authenticated-orcid":false,"given":"Nath\u00e1lia Alves Araujo","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia e Parasitologia Molecular, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6905-2007","authenticated-orcid":false,"given":"Tatiana","family":"Maron-Gutierrez","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040-361, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elen Mello","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia e Parasitologia Molecular, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Salete","family":"de Paula","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia e Parasitologia Molecular, Instituto Oswaldo Cruz\/FIOCRUZ, Rio de Janeiro 21040900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"001673","DOI":"10.1099\/jgv.0.001673","article-title":"ICTV Virus Taxonomy Profile: Herpesviridae 2021","volume":"102","author":"Gatherer","year":"2021","journal-title":"J. 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