{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:08:38Z","timestamp":1790741318852,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FPA","award":["FPA IDA08"],"award-info":[{"award-number":["FPA IDA08"]}]},{"DOI":"10.13039\/501100002830","name":"Centre National d\u2019Etudes Spatiales","doi-asserted-by":"crossref","award":["DAR CNES 4500072566,programme COSMIC"],"award-info":[{"award-number":["DAR CNES 4500072566,programme COSMIC"]}],"id":[{"id":"10.13039\/501100002830","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ANR","award":["ANR-20-CE37-0016 (programme INVEST)"],"award-info":[{"award-number":["ANR-20-CE37-0016 (programme INVEST)"]}]},{"name":"ANR","award":["ANR-22-CE37-0002-01 (programme LOCOGATE)"],"award-info":[{"award-number":["ANR-22-CE37-0002-01 (programme LOCOGATE)"]}]},{"name":"ANR","award":["EARGENCURE,ANR-17-CE18-0027"],"award-info":[{"award-number":["EARGENCURE,ANR-17-CE18-0027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,8]]},"abstract":"<jats:p>\n                    Neonatal gene therapy has been shown to prevent inner ear dysfunction in mouse models of Usher syndrome type I (USH1), the most common genetic cause of combined deafness-blindness and vestibular dysfunction. However, hearing onset occurs after birth in mice and in utero in humans, making it questionable how to transpose murine gene therapy outcomes to clinical settings. Here, we sought to extend the therapeutic time window in a mouse model for USH1G to periods corresponding to human neonatal stages, more suitable for intervention in patients. Mice with deletion of\n                    <jats:italic>Ush1g<\/jats:italic>\n                    (\n                    <jats:italic>\n                      Ush1g\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) were subjected to gene therapy after the hearing onset. The rescue of inner ear hair cell structure was evaluated by confocal imaging and electron microscopy. Hearing and vestibular function were assessed by recordings of the auditory brain stem response and vestibulo-ocular reflex and by locomotor tests. Up to P21, gene therapy significantly restored both the hearing and balance deficits in\n                    <jats:italic>\n                      Ush1g\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. However, beyond this age and up to P30, vestibular function was restored but not hearing. Our data show that effective gene therapy is possible in\n                    <jats:italic>\n                      Ush1g\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice well beyond neonatal stages, implying that the therapeutic window for USH1G may be wide enough to be transposable to newborn humans.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.169504","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T07:53:21Z","timestamp":1707897201000},"source":"Crossref","is-referenced-by-count":14,"title":["Extended time frame for restoring inner ear function through gene therapy in Usher1G preclinical model"],"prefix":"10.1172","volume":"9","author":[{"given":"Ghizlene","family":"Lahlou","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."},{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris, Sorbonne University, Service d\u2019ORL et de Chirurgie Cervico-Faciale, DMU ChIR, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Calvet","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Simon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Facult\u00e9 de M\u00e9decine, Paris, France."},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR 8002, INCC \u2014 Integrative Neuroscience and Cognition Center, Paris, France."},{"name":"Department of Pediatric Otolaryngology, Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Necker-Enfants Malades, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7025-4343","authenticated-orcid":true,"given":"Vincent","family":"Michel","sequence":"additional","affiliation":[{"name":"Institut Pasteur, INSERM, Pathogenesis of Vascular Infections Unit, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5928-1511","authenticated-orcid":true,"given":"Lauranne","family":"Alciato","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Plion","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Boutet de Monvel","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Beraneck","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS UMR 8002, INCC \u2014 Integrative Neuroscience and Cognition Center, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Petit","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."},{"name":"Coll\u00e8ge de France, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saaid","family":"Safieddine","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Inserm, Institut de l\u2019Audition, Paris, France."},{"name":"CNRS, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"B1"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3233\/NRE-130873"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000525577"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708894114"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817537116"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3801"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab1996"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.11.003"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.150"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32834ef8b2"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2008.02.013"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00830"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017114108"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2016.02.004"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-62630-1.00003-2"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2014.00011"},{"key":"B17"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.120"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3781"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/srep45524"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.05.009"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21233-z"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.05.007"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.204"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107934"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9020589"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2016.12.010"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.05.019"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2014.73"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08243-1"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.750596"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi031"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.025"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp429"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09960-8"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040414"},{"issue":"144","key":"B37","doi-asserted-by":"crossref","DOI":"10.3791\/59135","article-title":"Long-term sensory conflict in freely behaving mice","author":"Fran\u00e7a de Barros","year":"2019","journal-title":"J Vis Exp"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0290-16.2017"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.11.053"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/169504\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:42:28Z","timestamp":1779140548000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/169504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2,8]]},"published-print":{"date-parts":[[2024,2,8]]}},"alternative-id":["10.1172\/jci.insight.169504"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.169504","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]},"article-number":"e169504"}}