{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:21:37Z","timestamp":1778754097909,"version":"3.51.4"},"reference-count":112,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"am","delay-in-days":332,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100008569","name":"Oklahoma Center for the Advancement of Science and Technology","doi-asserted-by":"publisher","award":["AR15-05"],"award-info":[{"award-number":["AR15-05"]}],"id":[{"id":"10.13039\/100008569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC-014456"],"award-info":[{"award-number":["DC-014456"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC-014832"],"award-info":[{"award-number":["DC-014832"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-18-1-0017"],"award-info":[{"award-number":["W81XWH-18-1-0017"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Hearing Research"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.heares.2020.107981","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T11:48:47Z","timestamp":1588679327000},"page":"107981","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":35,"special_numbering":"C","title":["Gene therapy for hair cell regeneration: Review and new data"],"prefix":"10.1016","volume":"394","author":[{"given":"Seiji B.","family":"Shibata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew B.","family":"West","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichiro","family":"Iwasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yehoash","family":"Raphael","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard D.","family":"Kopke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.heares.2020.107981_bib1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0304-3940(96)12367-3","article-title":"New hair cells arise from supporting cell conversion in the acoustically damaged chick inner ear [published erratum appears in Neurosci Lett 1996 May 24;210(1):73]","volume":"205","author":"Adler","year":"1996","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.heares.2020.107981_bib2","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1001\/archinternmed.2009.66","article-title":"Disorders of balance and vestibular function in US adults: data from the national health and nutrition examination survey, 2001-2004","volume":"169","author":"Agrawal","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"10.1016\/j.heares.2020.107981_bib3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12551-017-0392-1","article-title":"Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer","volume":"10","author":"Ahmadzada","year":"2018","journal-title":"Biophys Rev"},{"key":"10.1016\/j.heares.2020.107981_bib4","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.devcel.2011.12.006","article-title":"Eya1-Six1 interaction is sufficient to induce hair cell fate in the cochlea by activating Atoh1 expression in cooperation with Sox2","volume":"22","author":"Ahmed","year":"2012","journal-title":"Dev. Cell"},{"key":"10.1016\/j.heares.2020.107981_bib5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0102077","article-title":"Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult Guinea pigs","volume":"9","author":"Atkinson","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.heares.2020.107981_bib6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1749-6632.1996.tb15693.x","article-title":"Mitotic and nonmitotic hair cell regeneration in the bullfrog vestibular otolith organs","volume":"781","author":"Baird","year":"1996","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.heares.2020.107981_bib7","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1749-6632.2001.tb03747.x","article-title":"Age-related changes in vestibular function: a longitudinal study","volume":"942","author":"Baloh","year":"2001","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.heares.2020.107981_bib8","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1093\/hmg\/5.9.1207","article-title":"Evolutionary conservation of sequence and expression of the bHLH protein Atonal suggests a conserved role in neurogenesis","volume":"5","author":"Ben-Arie","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.heares.2020.107981_bib9","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1242\/dev.127.5.1039","article-title":"Functional conservation of atonal and Math1 in the CNS and PNS","volume":"127","author":"Ben-Arie","year":"2000","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib10","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1126\/science.284.5421.1837","article-title":"Math1: an essential gene for the generation of inner ear hair cells","volume":"284","author":"Bermingham","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.heares.2020.107981_bib11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2009.02.028","article-title":"Feathers and fins: non-mammalian models for hair cell regeneration","volume":"1277","author":"Brignull","year":"2009","journal-title":"Brain Res."},{"key":"10.1016\/j.heares.2020.107981_bib12","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.arr.2015.12.007","article-title":"Molecular aging of the mammalian vestibular system","volume":"26","author":"Brosel","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.heares.2020.107981_bib13","doi-asserted-by":"crossref","DOI":"10.3390\/biom10030370","article-title":"Hear, hear for notch: control of cell fates in the inner ear by notch signaling","volume":"10","author":"Brown","year":"2020","journal-title":"Biomolecules"},{"key":"10.1016\/j.heares.2020.107981_bib14","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.18128","article-title":"Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice","volume":"6","author":"Bucks","year":"2017","journal-title":"eLife"},{"key":"10.1016\/j.heares.2020.107981_bib15","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s10162-012-0337-0","article-title":"Over half the hair cells in the mouse utricle first appear after birth, with significant numbers originating from early postnatal mitotic production in peripheral and striolar growth zones","volume":"13","author":"Burns","year":"2012","journal-title":"J\u00a0Assoc Res Otolaryngol"},{"key":"10.1016\/j.heares.2020.107981_bib16","doi-asserted-by":"crossref","first-page":"10110","DOI":"10.1523\/JNEUROSCI.5606-12.2013","article-title":"Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti","volume":"33","author":"Cai","year":"2013","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib17","doi-asserted-by":"crossref","first-page":"19484","DOI":"10.1038\/srep19484","article-title":"Canonical Notch signaling plays an instructive role in auditory supporting cell development","volume":"6","author":"Campbell","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.heares.2020.107981_bib18","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1242\/dev.126.8.1581","article-title":"p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti","volume":"126","author":"Chen","year":"1999","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib19","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1242\/dev.129.10.2495","article-title":"The role of Math1 in inner ear development: uncoupling the establishment of the sensory primordium from hair cell fate determination","volume":"129","author":"Chen","year":"2002","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib20","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ydbio.2013.06.022","article-title":"Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear","volume":"381","author":"Chonko","year":"2013","journal-title":"Dev. Biol."},{"key":"10.1016\/j.heares.2020.107981_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0023861","article-title":"Variations in shape-sensitive restriction points mirror differences in the regeneration capacities of avian and mammalian ears","volume":"6","author":"Collado","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.heares.2020.107981_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2018.03.002","article-title":"Epigenetic control of gene regulation during development and disease: a view from the retina","volume":"65","author":"Corso-Diaz","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.heares.2020.107981_bib23","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1242\/dev.119149","article-title":"Generation of sensory hair cells by genetic programming with a combination of transcription factors","volume":"142","author":"Costa","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib24","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1242\/dev.103036","article-title":"Spontaneous hair cell regeneration in the neonatal mouse cochlea in\u00a0vivo","volume":"141","author":"Cox","year":"2014","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib25","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1111\/j.1460-9568.2007.05355.x","article-title":"Developmental changes in cell-extracellular matrix interactions limit proliferation in the mammalian inner ear","volume":"25","author":"Davies","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.semcdb.2016.11.002","article-title":"Insights into inner ear-specific gene regulation: epigenetics and non-coding RNAs in inner ear development and regeneration","volume":"65","author":"Doetzlhofer","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1016\/j.heares.2020.107981_bib27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.heares.2013.06.011","article-title":"Regeneration of mammalian cochlear and vestibular hair cells through Hes1\/Hes5 modulation with siRNA","volume":"304","author":"Du","year":"2013","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib28","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.ymthe.2018.03.004","article-title":"Regeneration of cochlear hair cells and hearing recovery through Hes1 modulation with siRNA nanoparticles in adult Guinea pigs","volume":"26","author":"Du","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.heares.2020.107981_bib29","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev.med.56.082103.104606","article-title":"The silent revolution: RNA interference as basic biology, research tool, and therapeutic","volume":"56","author":"Dykxhoorn","year":"2005","journal-title":"Annu. Rev. Med."},{"key":"10.1016\/j.heares.2020.107981_bib30","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/381603a0","article-title":"Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development","volume":"381","author":"Erkman","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.heares.2020.107981_bib31","doi-asserted-by":"crossref","first-page":"7811","DOI":"10.1523\/JNEUROSCI.18-19-07811.1998","article-title":"Hair cells and supporting cells share a common progenitor in the avian inner ear","volume":"18","author":"Fekete","year":"1998","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib32","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1126\/science.8456284","article-title":"Ultrastructural evidence for hair cell regeneration in the mammalian inner ear","volume":"259","author":"Forge","year":"1993","journal-title":"Science"},{"key":"10.1016\/j.heares.2020.107981_bib33","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/stem.2554","article-title":"Concise review: regeneration in mammalian cochlea hair cells: help from supporting cells transdifferentiation","volume":"35","author":"Franco","year":"2017","journal-title":"Stem Cell."},{"key":"10.1016\/j.heares.2020.107981_bib34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.heares.2012.11.017","article-title":"Gene therapy for the inner ear","volume":"297","author":"Fukui","year":"2013","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib35","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s12035-015-9119-0","article-title":"Spatial and age-dependent hair cell generation in the postnatal mammalian utricle","volume":"53","author":"Gao","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.heares.2020.107981_bib36","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.otohns.2007.04.013","article-title":"Distribution of PLGA nanoparticles in chinchilla cochleae","volume":"137","author":"Ge","year":"2007","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"10.1016\/j.heares.2020.107981_bib37","doi-asserted-by":"crossref","first-page":"15093","DOI":"10.1523\/JNEUROSCI.1709-12.2012","article-title":"Hair cell replacement in adult mouse utricles after targeted ablation of hair cells with diphtheria toxin","volume":"32","author":"Golub","year":"2012","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib38","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature07265","article-title":"Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer","volume":"455","author":"Gubbels","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.heares.2020.107981_bib39","series-title":"A\u00a0Critical E-Box in Barhl1 3\u2019 Enhancer Is Essential for Auditory Hair Cell Differentiation. Cells 8","author":"Hou","year":"2019"},{"key":"10.1016\/j.heares.2020.107981_bib40","doi-asserted-by":"crossref","DOI":"10.1002\/jgm.3097","article-title":"Clinical advances of siRNA therapeutics","volume":"21","author":"Hu","year":"2019","journal-title":"J.\u00a0Gene Med."},{"key":"10.1016\/j.heares.2020.107981_bib41","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1055\/s-0029-1241039","article-title":"Imbalance and vertigo: the aging human vestibular periphery","volume":"29","author":"Ishiyama","year":"2009","journal-title":"Semin. Neurol."},{"key":"10.1016\/j.heares.2020.107981_bib42","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.heares.2008.02.007","article-title":"Response of the flat cochlear epithelium to forced expression of Atoh1","volume":"240","author":"Izumikawa","year":"2008","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib43","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nm1193","article-title":"Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals","volume":"11","author":"Izumikawa","year":"2005","journal-title":"Nat. Med."},{"key":"10.1016\/j.heares.2020.107981_bib44","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fncel.2015.00026","article-title":"Opportunities and limits of the one gene approach: the ability of Atoh1 to differentiate and maintain hair cells depends on the molecular context","volume":"9","author":"Jahan","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v28.i1.10","article-title":"Engineered PLGA nanoparticles: an emerging delivery tool in cancer therapeutics","volume":"28","author":"Jain","year":"2011","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"10.1016\/j.heares.2020.107981_bib46","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.44328","article-title":"Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1","volume":"8","author":"Jen","year":"2019","journal-title":"eLife"},{"key":"10.1016\/j.heares.2020.107981_bib47","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1021\/mp900093r","article-title":"Biological barriers to therapy with antisense and siRNA oligonucleotides","volume":"6","author":"Juliano","year":"2009","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.heares.2020.107981_bib48","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/mt.2013.18","article-title":"siRNA targeting Hes5 augments hair cell regeneration in aminoglycoside-damaged mouse utricle","volume":"21","author":"Jung","year":"2013","journal-title":"Mol. Ther."},{"key":"10.1016\/j.heares.2020.107981_bib49","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1523\/JNEUROSCI.23-11-04395.2003","article-title":"Math1 gene transfer generates new cochlear hair cells in mature Guinea pigs in\u00a0vivo","volume":"23","author":"Kawamoto","year":"2003","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib50","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.heares.2008.08.010","article-title":"Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity","volume":"247","author":"Kawamoto","year":"2009","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib51","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nrn1987","article-title":"Regulation of cell fate in the sensory epithelia of the inner ear","volume":"7","author":"Kelley","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib52","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1523\/JNEUROSCI.5420-11.2012","article-title":"Atoh1 directs the formation of sensory mosaics and induces cell proliferation in the postnatal mammalian cochlea in\u00a0vivo","volume":"32","author":"Kelly","year":"2012","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib53","doi-asserted-by":"crossref","first-page":"612","DOI":"10.4161\/cc.6.5.3929","article-title":"Cell division and maintenance of epithelial integrity in the deafened auditory epithelium","volume":"6","author":"Kim","year":"2007","journal-title":"Cell Cycle"},{"key":"10.1016\/j.heares.2020.107981_bib54","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1159\/000090685","article-title":"Magnetic nanoparticles: inner ear targeted molecule delivery and middle ear implant","volume":"11","author":"Kopke","year":"2006","journal-title":"Audiol. Neuro. Otol."},{"key":"10.1016\/j.heares.2020.107981_bib55","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1002\/lary.22171","article-title":"Atoh1 induces auditory hair cell recovery in mice after ototoxic injury","volume":"123","author":"Kraft","year":"2013","journal-title":"Laryngoscope"},{"key":"10.1016\/j.heares.2020.107981_bib56","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ydbio.2009.10.027","article-title":"Cell cycle regulation in the inner ear sensory epithelia: role of cyclin D1 and cyclin-dependent kinase inhibitors","volume":"337","author":"Laine","year":"2010","journal-title":"Dev. Biol."},{"key":"10.1016\/j.heares.2020.107981_bib57","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1523\/JNEUROSCI.4956-06.2007","article-title":"p19(Ink4d) and p21(Cip1) collaborate to maintain the postmitotic state of auditory hair cells, their codeletion leading to DNA damage and p53-mediated apoptosis","volume":"27","author":"Laine","year":"2007","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib58","doi-asserted-by":"crossref","first-page":"496","DOI":"10.18632\/aging.100668","article-title":"DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells","volume":"6","author":"Laos","year":"2014","journal-title":"Aging"},{"key":"10.1016\/j.heares.2020.107981_bib59","first-page":"446","article-title":"Epigenetic regulation in the inner ear and its potential roles in development, protection, and regeneration","volume":"8","author":"Layman","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib60","doi-asserted-by":"crossref","first-page":"107934","DOI":"10.1016\/j.heares.2020.107934","article-title":"Practical aspects of inner ear gene delivery for research and clinical applications","author":"Lee","year":"2020","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib61","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1242\/dev.129.14.3523","article-title":"Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1 homeobox gene","volume":"129","author":"Li","year":"2002","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib62","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1001\/archneurol.2010.362","article-title":"Hearing loss and incident dementia","volume":"68","author":"Lin","year":"2011","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.heares.2020.107981_bib63","doi-asserted-by":"crossref","first-page":"6600","DOI":"10.1523\/JNEUROSCI.0818-12.2012","article-title":"Age-dependent in\u00a0vivo conversion of mouse cochlear pillar and Deiters\u2019 cells to immature hair cells by Atoh1 ectopic expression","volume":"32","author":"Liu","year":"2012","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib64","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","article-title":"Dementia prevention, intervention, and care","volume":"390","author":"Livingston","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.heares.2020.107981_bib65","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0027360","article-title":"Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression","volume":"6","author":"Loponen","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.heares.2020.107981_bib66","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1073\/pnas.96.7.4084","article-title":"Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti","volume":"96","author":"Lowenheim","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.heares.2020.107981_bib67","doi-asserted-by":"crossref","first-page":"107927","DOI":"10.1016\/j.heares.2020.107927","article-title":"Viral vectors for gene delivery to the inner ear","author":"Maguire","year":"2020","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib68","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1242\/dev.01834","article-title":"The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear","volume":"132","author":"Mantela","year":"2005","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib69","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/0378-5955(94)90124-4","article-title":"Scar formation in the vestibular sensory epithelium after aminoglycoside toxicity","volume":"79","author":"Meiteles","year":"1994","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib70","doi-asserted-by":"crossref","first-page":"16919","DOI":"10.1073\/pnas.1408064111","article-title":"Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse","volume":"111","author":"Mellado Lagarde","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.heares.2020.107981_bib71","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.heares.2007.06.005","article-title":"Manipulating cell cycle regulation in the mature cochlea","volume":"232","author":"Minoda","year":"2007","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib72","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.neuron.2012.10.032","article-title":"Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma","volume":"77","author":"Mizutari","year":"2013","journal-title":"Neuron"},{"key":"10.1016\/j.heares.2020.107981_bib73","first-page":"561","article-title":"Nanoparticles - a review","volume":"5","author":"Mohanraj","year":"2006","journal-title":"Trop. J. Pharmaceut. Res."},{"key":"10.1016\/j.heares.2020.107981_bib74","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1001\/archinte.168.19.2118","article-title":"Burden of dizziness and vertigo in the community","volume":"168","author":"Neuhauser","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"10.1016\/j.heares.2020.107981_bib75","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/bs.pmbts.2018.04.002","article-title":"An introduction to epigenetic mechanisms","volume":"158","author":"Radford","year":"2018","journal-title":"Prog Mol Biol Transl Sci"},{"key":"10.1016\/j.heares.2020.107981_bib76","first-page":"28","article-title":"Cell division in the gerbil cochlea after acoustic trauma","volume":"15","author":"Roberson","year":"1994","journal-title":"Am. J. Otol."},{"key":"10.1016\/j.heares.2020.107981_bib77","doi-asserted-by":"crossref","first-page":"7345","DOI":"10.1073\/pnas.0510631103","article-title":"Essential role of retinoblastoma protein in mammalian hair cell development and hearing","volume":"103","author":"Sage","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.heares.2020.107981_bib78","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1126\/science.1106642","article-title":"Proliferation of functional hair cells in\u00a0vivo in the absence of the retinoblastoma protein","volume":"307","author":"Sage","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.heares.2020.107981_bib79","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.ymthe.2019.03.017","article-title":"Therapeutic potential of wnt and notch signaling and epigenetic regulation in mammalian sensory hair cell regeneration","volume":"27","author":"Samarajeewa","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.heares.2020.107981_bib80","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.celrep.2019.06.028","article-title":"Atoh1 directs regeneration and functional recovery of the mature mouse vestibular system","volume":"28","author":"Sayyid","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.heares.2020.107981_bib81","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/gt.2011.33","article-title":"Selective atonal gene delivery improves balance function in a mouse model of vestibular disease","volume":"18","author":"Schlecker","year":"2011","journal-title":"Gene Ther."},{"key":"10.1016\/j.heares.2020.107981_bib82","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1044-7431(03)00066-6","article-title":"Robust generation of new hair cells in the mature mammalian inner ear by adenoviral expression of Hath1","volume":"23","author":"Shou","year":"2003","journal-title":"Mol. Cell. Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib83","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s10162-013-0414-z","article-title":"Hair cell generation by notch inhibition in the adult mammalian cristae","volume":"14","author":"Slowik","year":"2013","journal-title":"J\u00a0Assoc Res Otolaryngol"},{"key":"10.1016\/j.heares.2020.107981_bib84","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3109\/00016489609137836","article-title":"Post-traumatic survival and recovery of the auditory sensory cells in culture","volume":"116","author":"Sobkowicz","year":"1996","journal-title":"Acta Otolaryngol."},{"key":"10.1016\/j.heares.2020.107981_bib85","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0736-5748(96)00104-9","article-title":"Cellular interactions as a response to injury in the organ of Corti in culture","volume":"15","author":"Sobkowicz","year":"1997","journal-title":"Int. J. Dev. Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib86","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/MAO.0b013e31802b3225","article-title":"Vestibular hair cell regeneration and restoration of balance function induced by math1 gene transfer","volume":"28","author":"Staecker","year":"2007","journal-title":"Otol. Neurotol."},{"issue":"Suppl.\u00a05","key":"10.1016\/j.heares.2020.107981_bib87","first-page":"S1","article-title":"Optimizing atoh1-induced vestibular hair cell regeneration","volume":"124","author":"Staecker","year":"2014","journal-title":"Laryngoscope"},{"key":"10.1016\/j.heares.2020.107981_bib88","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1242\/dev.126763","article-title":"Epigenetic regulation of Atoh1 guides hair cell development in the mammalian cochlea","volume":"142","author":"Stojanova","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib89","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.actbio.2018.04.006","article-title":"Customizing poly(lactic-co-glycolic acid) particles for biomedical applications","volume":"73","author":"Swider","year":"2018","journal-title":"Acta Biomater."},{"key":"10.1016\/j.heares.2020.107981_bib90","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1097\/01.mlg.0000180174.81036.5a","article-title":"Drug delivery to the cochlea using PLGA nanoparticles","volume":"115","author":"Tamura","year":"2005","journal-title":"Laryngoscope"},{"key":"10.1016\/j.heares.2020.107981_bib91","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1038\/s41467-019-11687-8","article-title":"AAV-ie enables safe and efficient gene transfer to inner ear cells","volume":"10","author":"Tan","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.heares.2020.107981_bib92","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.34817","article-title":"Regenerating hair cells in vestibular sensory epithelia from humans","volume":"7","author":"Taylor","year":"2018","journal-title":"eLife"},{"key":"10.1016\/j.heares.2020.107981_bib93","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1016\/j.neurobiolaging.2015.02.013","article-title":"Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing","volume":"36","author":"Taylor","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.heares.2020.107981_bib94","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1242\/dev.00190","article-title":"The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival","volume":"130","author":"Wallis","year":"2003","journal-title":"Development"},{"key":"10.1016\/j.heares.2020.107981_bib95","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.heares.2012.11.009","article-title":"Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration","volume":"297","author":"Walters","year":"2013","journal-title":"Hear. Res."},{"key":"10.1016\/j.heares.2020.107981_bib96","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.celrep.2017.03.044","article-title":"In\u00a0vivo interplay between p27(kip1), GATA3, ATOH1, and POU4F3 converts non-sensory cells to hair cells in adult mice","volume":"19","author":"Walters","year":"2017","journal-title":"Cell Rep."},{"key":"10.1016\/j.heares.2020.107981_bib97","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.semcdb.2013.03.009","article-title":"Inner ear supporting cells: rethinking the silent majority","volume":"24","author":"Wan","year":"2013","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1016\/j.heares.2020.107981_bib98","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1126\/science.8456285","article-title":"Regenerative proliferation in inner ear sensory epithelia from adult Guinea pigs and humans","volume":"259","author":"Warchol","year":"1993","journal-title":"Science"},{"key":"10.1016\/j.heares.2020.107981_bib99","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/nature04849","article-title":"Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells","volume":"441","author":"White","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.heares.2020.107981_bib100","series-title":"Global Costs of Unaddressed Hearing Loss and Cost-Effectiveness of Interventions","author":"WHO","year":"2017"},{"key":"10.1016\/j.heares.2020.107981_bib101","author":"WHO"},{"key":"10.1016\/j.heares.2020.107981_bib102","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/nn1349","article-title":"Math1 regulates development of the sensory epithelium in the mammalian cochlea","volume":"7","author":"Woods","year":"2004","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.heares.2020.107981_bib103","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1166\/jbn.2013.1684","article-title":"In\u00a0vivo delivery of Atoh1 gene to rat cochlea using a dendrimer-based nanocarrier","volume":"9","author":"Wu","year":"2013","journal-title":"J.\u00a0Biomed. Nanotechnol."},{"key":"10.1016\/j.heares.2020.107981_bib104","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1101\/SQB.1997.062.01.039","article-title":"Role of the Brn-3 family of POU-domain genes in the development of the auditory\/vestibular, somatosensory, and visual systems","volume":"62","author":"Xiang","year":"1997","journal-title":"Cold Spring Harbor Symp. Quant. Biol."},{"key":"10.1016\/j.heares.2020.107981_bib105","first-page":"819","article-title":"Type I hair cell regeneration induced by Math1 gene transfer following neomycin ototoxicity in rat vestibular sensory epithelium","volume":"132","author":"Xu","year":"2012","journal-title":"Acta Otolaryngol."},{"key":"10.1016\/j.heares.2020.107981_bib106","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007552","article-title":"High-resolution transcriptional dissection of in\u00a0vivo Atoh1-mediated hair cell conversion in mature cochleae identifies Isl1 as a co-reprogramming factor","volume":"14","author":"Yamashita","year":"2018","journal-title":"PLoS Genet."},{"key":"10.1016\/j.heares.2020.107981_bib107","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.jconrel.2014.06.038","article-title":"Insight into nanoparticle cellular uptake and intracellular targeting","volume":"190","author":"Yameen","year":"2014","journal-title":"J.\u00a0Contr. Release"},{"key":"10.1016\/j.heares.2020.107981_bib108","article-title":"Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea","volume":"7","author":"Yang","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.heares.2020.107981_bib109","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1016\/j.xphs.2016.04.012","article-title":"Label-free ferrocene-loaded nanocarrier engineering for in\u00a0vivo cochlear drug delivery and imaging","volume":"105","author":"Youm","year":"2016","journal-title":"J.\u00a0Pharmaceut. Sci."},{"key":"10.1016\/j.heares.2020.107981_bib110","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.ijpharm.2017.06.035","article-title":"siRNA-loaded biodegradable nanocarriers for therapeutic MAPK1 silencing against cisplatin-induced ototoxicity","volume":"528","author":"Youm","year":"2017","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.heares.2020.107981_bib111","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2147\/IJN.S154968","article-title":"Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine","volume":"13","author":"Zhang","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.heares.2020.107981_bib112","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/75753","article-title":"Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears","volume":"3","author":"Zheng","year":"2000","journal-title":"Nat. Neurosci."}],"container-title":["Hearing Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378595519304964?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378595519304964?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:36:54Z","timestamp":1778751414000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378595519304964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":112,"alternative-id":["S0378595519304964"],"URL":"https:\/\/doi.org\/10.1016\/j.heares.2020.107981","relation":{},"ISSN":["0378-5955"],"issn-type":[{"value":"0378-5955","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gene therapy for hair cell regeneration: Review and new data","name":"articletitle","label":"Article Title"},{"value":"Hearing Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.heares.2020.107981","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"107981"}}