{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:27:58Z","timestamp":1790015278933,"version":"4.0.1"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":40,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-DC016932"],"award-info":[{"award-number":["R01-DC016932"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["PCEFP3_202756,310030_192665"],"award-info":[{"award-number":["PCEFP3_202756,310030_192665"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["T32-GM007748"],"award-info":[{"award-number":["T32-GM007748"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-DC020190"],"award-info":[{"award-number":["R01-DC020190"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,2]]},"abstract":"<jats:p>\n                    Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (\n                    <jats:italic>PCDH15<\/jats:italic>\n                    ) gene, is characterized by congenital lack of hearing and balance, and progressive blindness in the form of retinitis pigmentosa. In this study, we explore an approach for\n                    <jats:italic>USH1F<\/jats:italic>\n                    gene therapy, exceeding the single AAV packaging limit by employing a dual\u2013adeno-associated virus (dual-AAV) strategy to deliver the full-length\n                    <jats:italic>PCDH15<\/jats:italic>\n                    coding sequence. We demonstrate the efficacy of this strategy in mouse USH1F models, effectively restoring hearing and balance in these mice. Importantly, our approach also proves successful in expressing PCDH15 protein in clinically relevant retinal models, including human retinal organoids and nonhuman primate retina, showing efficient targeting of photoreceptors and proper protein expression in the calyceal processes. This research represents a major step toward advancing gene therapy for USH1F and the multiple challenges of hearing, balance, and vision impairment.\n                  <\/jats:p>","DOI":"10.1172\/jci177700","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T13:18:43Z","timestamp":1729689523000},"source":"Crossref","is-referenced-by-count":26,"title":["PCDH15 dual-AAV gene therapy for deafness and blindness in Usher syndrome type 1F models"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0754-1427","authenticated-orcid":true,"given":"Maryna V.","family":"Ivanchenko","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Hathaway","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Mulhall","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin T.A.","family":"Booth","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mantian","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland."},{"name":"Department of Ophthalmology, University of Basel, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole W.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex J.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Gy\u00f6rgy","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland."},{"name":"Department of Ophthalmology, University of Basel, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Corey","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107932"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00183"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0000000000002054"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.11.020"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1086\/321277"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg358"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.16.1709"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1163-06.2006"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature06091"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature11590"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90343-X"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67361"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69740-7"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15020685"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn140"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/83837"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1242\/dev.060061"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22456"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019183"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38770"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13458"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920444117"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201202012"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02998-y"},{"key":"B25","unstructured":"US Food and Drug Administration. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-novel-gene-therapy-treat-patients-rare-form-inherited-vision-loss Updated December 18, 2017. Accessed October 9, 2024"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041278"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38038-y"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.06.007"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0456"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6716"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809396"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201302948"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300322"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817537116"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03023-5"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02874-X"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2023.08.012"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2019.132"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2013.212"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201403976"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1089\/10430340360464697"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107912"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.11.003"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107930"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107882"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017114108"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.08.006"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103837"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00597-7"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12031046"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.02.001"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107927"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2019"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.29533"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2023.126"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1097\/IIO.0000000000000378"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107931"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6274-11.2012"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.09.002"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3239"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01747-2"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.013"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-27681-1_80"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/164_2023_691"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.03.008"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.11.029"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11712-w"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.744248"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/177700\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:59:07Z","timestamp":1779231547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/177700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,23]]},"references-count":68,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12,2]]},"published-print":{"date-parts":[[2024,12,2]]}},"alternative-id":["10.1172\/JCI177700"],"URL":"https:\/\/doi.org\/10.1172\/jci177700","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,23]]},"article-number":"e177700"}}