{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:35:55Z","timestamp":1791959755293,"version":"4.3.4"},"reference-count":45,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.ymthe.2020.11.016","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T21:06:21Z","timestamp":1605560781000},"page":"973-988","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":76,"title":["Single and Dual Vector Gene Therapy with AAV9-PHP.B Rescues Hearing in Tmc1 Mutant Mice"],"prefix":"10.1016","volume":"29","author":[{"given":"Jason","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Solanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Nist-Lund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Spataro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Shubina-Oleinik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Marcovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard L.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-8011","authenticated-orcid":false,"given":"Jeffrey R.","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2020.11.016_bib1","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1093\/hmg\/ddz129","article-title":"Gene therapy for hearing loss","volume":"28","author":"Omichi","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2020.11.016_bib2","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0140-6736(05)71047-3","article-title":"Sensorineural hearing loss in children","volume":"365","author":"Smith","year":"2005","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2020.11.016_bib3","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/ajmg.1320460504","article-title":"Genetic epidemiological studies of early-onset deafness in the U.S. school-age population","volume":"46","author":"Marazita","year":"1993","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.ymthe.2020.11.016_bib4","doi-asserted-by":"crossref","first-page":"108010","DOI":"10.1016\/j.heares.2020.108010","article-title":"Introduction to the Hearing Research special issue on inner ear gene therapy","volume":"394","author":"Holt","year":"2020","journal-title":"Hear. Res."},{"key":"10.1016\/j.ymthe.2020.11.016_bib5","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41467-018-08264-w","article-title":"Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders","volume":"10","author":"Nist-Lund","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2020.11.016_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.omtm.2018.11.003","article-title":"Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate","volume":"13","author":"Gy\u00f6rgy","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2020.11.016_bib7","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ymthe.2016.12.010","article-title":"Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV","volume":"25","author":"Gy\u00f6rgy","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2020.11.016_bib8","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nm.3106","article-title":"Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness","volume":"19","author":"Lentz","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2020.11.016_bib9","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.ajhg.2016.03.028","article-title":"RNA Interference Prevents Autosomal-Dominant Hearing Loss","volume":"98","author":"Shibata","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ymthe.2020.11.016_bib10","doi-asserted-by":"crossref","first-page":"eaay9101","DOI":"10.1126\/scitranslmed.aay9101","article-title":"In\u00a0vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness","volume":"12","author":"Yeh","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2020.11.016_bib11","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s41591-019-0500-9","article-title":"Allele-specific gene editing prevents deafness in a model of dominant progressive hearing loss","volume":"25","author":"Gy\u00f6rgy","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2020.11.016_bib12","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.neuron.2018.07.033","article-title":"TMC1 Forms the Pore of Mechanosensory Transduction Channels in Vertebrate Inner Ear Hair Cells","volume":"99","author":"Pan","year":"2018","journal-title":"Neuron"},{"key":"10.1016\/j.ymthe.2020.11.016_bib13","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.neuron.2013.06.019","article-title":"TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear","volume":"79","author":"Pan","year":"2013","journal-title":"Neuron"},{"key":"10.1016\/j.ymthe.2020.11.016_bib14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.neuron.2019.10.017","article-title":"TMC1 and TMC2 Proteins Are Pore-Forming Subunits of Mechanosensitive Ion Channels","volume":"105","author":"Jia","year":"2020","journal-title":"Neuron"},{"key":"10.1016\/j.ymthe.2020.11.016_bib15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10048-016-0477-1","article-title":"Recessive mutations of TMC1 associated with moderate to severe hearing loss","volume":"17","author":"Imtiaz","year":"2016","journal-title":"Neurogenetics"},{"key":"10.1016\/j.ymthe.2020.11.016_bib16","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00439-016-1648-8","article-title":"Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss","volume":"135","author":"Sloan-Heggen","year":"2016","journal-title":"Hum. Genet."},{"key":"10.1016\/j.ymthe.2020.11.016_bib17","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.1172\/JCI60405","article-title":"Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes","volume":"121","author":"Kawashima","year":"2011","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ymthe.2020.11.016_bib18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nbt.3440","article-title":"Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain","volume":"34","author":"Deverman","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2020.11.016_bib19","doi-asserted-by":"crossref","first-page":"107882","DOI":"10.1016\/j.heares.2020.107882","article-title":"Efficient viral transduction in mouse inner ear hair cells with utricle injection and AAV9-PHP.B","volume":"394","author":"Lee","year":"2020","journal-title":"Hear. Res."},{"key":"10.1016\/j.ymthe.2020.11.016_bib20","doi-asserted-by":"crossref","first-page":"295ra108","DOI":"10.1126\/scitranslmed.aab1996","article-title":"Tmc gene therapy restores auditory function in deaf mice","volume":"7","author":"Askew","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2020.11.016_bib21","doi-asserted-by":"crossref","first-page":"107930","DOI":"10.1016\/j.heares.2020.107930","article-title":"Preclinical testing of AAV9-PHP.B for transgene expression in the non-human primate cochlea","volume":"394","author":"Ivanchenko","year":"2020","journal-title":"Hear. Res."},{"key":"10.1016\/j.ymthe.2020.11.016_bib22","doi-asserted-by":"crossref","first-page":"4496","DOI":"10.1073\/pnas.1817537116","article-title":"Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model","volume":"116","author":"Akil","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2020.11.016_bib23","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.ajpath.2011.12.034","article-title":"Identification of three novel hearing loss mouse strains with mutations in the Tmc1 gene","volume":"180","author":"Manji","year":"2012","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.ymthe.2020.11.016_bib24","doi-asserted-by":"crossref","first-page":"e9995","DOI":"10.15252\/emmm.201809995","article-title":"Split otoferlins reunited","volume":"11","author":"Holt","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ymthe.2020.11.016_bib25","doi-asserted-by":"crossref","first-page":"107912","DOI":"10.1016\/j.heares.2020.107912","article-title":"Dual and triple AAV delivery of large therapeutic gene sequences into the inner ear","volume":"394","author":"Akil","year":"2020","journal-title":"Hear. Res."},{"key":"10.1016\/j.ymthe.2020.11.016_bib26","doi-asserted-by":"crossref","first-page":"107857","DOI":"10.1016\/j.heares.2019.107857","article-title":"Dual-AAV delivery of large gene sequences to the inner ear","volume":"394","author":"Reisinger","year":"2020","journal-title":"Hear. Res."},{"key":"10.1016\/j.ymthe.2020.11.016_bib27","doi-asserted-by":"crossref","first-page":"eaan8081","DOI":"10.1126\/scitranslmed.aan8081","article-title":"Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy","volume":"9","author":"Amoasii","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2020.11.016_bib28","doi-asserted-by":"crossref","first-page":"e9396","DOI":"10.15252\/emmm.201809396","article-title":"A dual-AAV approach restores fast exocytosis and partially rescues auditory function in deaf otoferlin knock-out mice","volume":"11","author":"Al-Moyed","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ymthe.2020.11.016_bib29","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.omtm.2020.05.007","article-title":"Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae","volume":"17","author":"Omichi","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2020.11.016_bib30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature25164","article-title":"Treatment of autosomal dominant hearing loss by in\u00a0vivo delivery of genome editing agents","volume":"553","author":"Gao","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2020.11.016_bib31","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1093\/nar\/gky164","article-title":"Easy quantification of template-directed CRISPR\/Cas9 editing","volume":"46","author":"Brinkman","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2020.11.016_bib32","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1093\/nar\/gku936","article-title":"Easy quantitative assessment of genome editing by sequence trace decomposition","volume":"42","author":"Brinkman","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2020.11.016_bib33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/ng848","article-title":"Beethoven, a mouse model for dominant, progressive hearing loss DFNA36","volume":"30","author":"Vreugde","year":"2002","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2020.11.016_bib34","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1016\/j.ymthe.2017.08.004","article-title":"AAV-PHP.B-Mediated Global-Scale Expression in the Mouse Nervous System Enables GBA1 Gene Therapy for Wide Protection from Synucleinopathy","volume":"25","author":"Morabito","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2020.11.016_bib35","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/hmg\/ddx438","article-title":"Cas9\/sgRNA selective targeting of the P23H Rhodopsin mutant allele for treating retinitis pigmentosa by intravitreal AAV9.PHP.B-based delivery","volume":"27","author":"Giannelli","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2020.11.016_bib36","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1089\/hum.2014.057","article-title":"Manufacturing and characterization of a recombinant adeno-associated virus type 8 reference standard material","volume":"25","author":"Ayuso","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2020.11.016_bib37","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nbt.3781","article-title":"A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear","volume":"35","author":"Landegger","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2020.11.016_bib38","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41467-018-08243-1","article-title":"AAV2.7m8 is a powerful viral vector for inner ear gene therapy","volume":"10","author":"Isgrig","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2020.11.016_bib39","doi-asserted-by":"crossref","first-page":"e0225206","DOI":"10.1371\/journal.pone.0225206","article-title":"Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids","volume":"14","author":"Huang","year":"2019","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2020.11.016_bib40","doi-asserted-by":"crossref","first-page":"e97064","DOI":"10.1371\/journal.pone.0097064","article-title":"A novel DFNA36 mutation in TMC1 orthologous to the Beethoven (Bth) mouse associated with autosomal dominant hearing loss in a Chinese family","volume":"9","author":"Zhao","year":"2014","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2020.11.016_bib41","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1113\/jphysiol.2005.095661","article-title":"Tmc1 is necessary for normal functional maturation and survival of inner and outer hair cells in the mouse cochlea","volume":"574","author":"Marcotti","year":"2006","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.ymthe.2020.11.016_bib42","doi-asserted-by":"crossref","first-page":"16019","DOI":"10.1038\/mtm.2016.19","article-title":"Practical utilization of recombinant AAV vector reference standards: focus on vector genomes titration by free ITR qPCR","volume":"5","author":"D\u2019Costa","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2020.11.016_bib43","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/biot.201400529","article-title":"CRISPR genome engineering and viral gene delivery: a case of mutual attraction","volume":"10","author":"Schmidt","year":"2015","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymthe.2020.11.016_bib44","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/j.cell.2013.12.001","article-title":"Dynamic imaging of genomic loci in living human cells by an optimized CRISPR\/Cas system","volume":"155","author":"Chen","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2020.11.016_bib45","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/excr.1999.4656","article-title":"Isolation and characterization of a near-haploid human cell line","volume":"252","author":"Kotecki","year":"1999","journal-title":"Exp. Cell Res."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001620306146?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001620306146?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:03:01Z","timestamp":1761501781000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001620306146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["S1525001620306146"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2020.11.016","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Single and Dual Vector Gene Therapy with AAV9-PHP.B Rescues Hearing in Tmc1 Mutant Mice","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2020.11.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Author(s).","name":"copyright","label":"Copyright"}]}}