{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:14:44Z","timestamp":1779138884303,"version":"3.51.4"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01-EY025295"],"award-info":[{"award-number":["R01-EY025295"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01-EY032159"],"award-info":[{"award-number":["R01-EY032159"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,20]]},"abstract":"<jats:p>\n                    Retinitis pigmentosa (RP) is a complex group of inherited retinal diseases characterized by progressive death of photoreceptor cells and eventual blindness.\n                    <jats:italic>Pde6a<\/jats:italic>\n                    , which encodes a cGMP-specific phosphodiesterase, is a crucial pathogenic gene for autosomal recessive RP (RP43); there is no effective therapy for this form of RP. The compact CRISPR\/\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    Cas9 (CRISPR\/SaCas9) system, which can be packaged into a single adeno-associated virus (AAV), holds promise for simplifying effective gene therapy. Here, we demonstrated that all-in-one AAV-SaCas9\u2013mediated\n                    <jats:italic>Nrl<\/jats:italic>\n                    gene inactivation can efficiently prevent retinal degeneration in a RP mouse model with\n                    <jats:italic>Pde6a<\/jats:italic>\n                    <jats:sup>nmf363\/nmf363<\/jats:sup>\n                    mutation. We screened single-guide RNAs capable of efficiently editing the mouse\n                    <jats:italic>Nrl<\/jats:italic>\n                    gene in N2a cells and then achieved effective gene editing by using a single AAV to codeliver SaCas9 and an optimal\n                    <jats:italic>Nrl<\/jats:italic>\n                    -sg2 into the mouse retina. Excitingly, in vivo inactivation of\n                    <jats:italic>Nrl<\/jats:italic>\n                    improved photoreceptor cell survival and rescued retinal function in treated\n                    <jats:italic>Pde6a-<\/jats:italic>\n                    deficient mice. Thus, we showed that a practical, gene-independent method, AAV-SaCas9\u2013mediated\n                    <jats:italic>Nrl<\/jats:italic>\n                    inactivation, holds promise for future therapeutic applications in patients with RP.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.178159","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T16:19:32Z","timestamp":1730823572000},"source":"Crossref","is-referenced-by-count":2,"title":["All-in-one AAV-mediated Nrl gene inactivation rescues retinal degeneration in Pde6a mice"],"prefix":"10.1172","volume":"9","author":[{"given":"Zhiquan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Hui","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8735-4765","authenticated-orcid":true,"given":"Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."},{"name":"Palo Alto Veterans Administration, Palo Alto, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-95046-4_25"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0039-6257(88)90085-9"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15020685"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S365486"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv275"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-468"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.22.10177"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-27378-1_17"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2020.4206"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.5.9"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072224"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/genes14071325"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214387110"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5011"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-021-2057-0"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.add8643"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14716"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.57"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.04.017"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nature14299"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.06.013"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14500"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1089\/crispr.2021.0143"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0327-9"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aar3952"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.04.049"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5177"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn327"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013392"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2022.109"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05391-2"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0817-8"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2022.12.003"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1089\/crispr.2021.0141"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210104119"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2023.108317"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI120429"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2316118121"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202308095"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01009-z"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-021-00868-6"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.031"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01857-x"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj6856"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01898-9"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv537"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku936"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu048"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0032-3"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34682-y"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.05.031"}],"container-title":["JCI 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