{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:29:15Z","timestamp":1787700555909,"version":"build-2784847793"},"reference-count":141,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation Recherche M\u00e9dicale","award":["REP202110014234"],"award-info":[{"award-number":["REP202110014234"]}]},{"name":"Fondation Recherche M\u00e9dicale","award":["65-2022"],"award-info":[{"award-number":["65-2022"]}]},{"name":"Fondation Gueules Cass\u00e9es","award":["REP202110014234"],"award-info":[{"award-number":["REP202110014234"]}]},{"name":"Fondation Gueules Cass\u00e9es","award":["65-2022"],"award-info":[{"award-number":["65-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by an impaired transmission of sound from the cochlea to the brain. This defect can be due to a lesion or defect in the inner hair cell (IHC), IHC ribbon synapse (e.g., pre-synaptic release of glutamate), postsynaptic terminals of the spiral ganglion neurons, or demyelination and axonal loss within the auditory nerve. To date, the only clinical treatment options for ANSD are hearing aids and cochlear implantation. However, despite the advances in hearing-aid and cochlear-implant technologies, the quality of perceived sound still cannot match that of the normal ear. Recent advanced genetic diagnostics and clinical audiology made it possible to identify the precise site of a lesion and to characterize the specific disease mechanisms of ANSD, thus bringing renewed hope to the treatment or prevention of auditory neurodegeneration. Moreover, genetic routes involving the replacement or corrective editing of mutant sequences or defected genes to repair damaged cells for the future restoration of hearing in deaf people are showing promise. In this review, we provide an update on recent discoveries in the molecular pathophysiology of genetic lesions, auditory synaptopathy and neuropathy, and gene-therapy research towards hearing restoration in rodent models and in clinical trials.<\/jats:p>","DOI":"10.3390\/jcm12030738","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T04:28:47Z","timestamp":1673929727000},"page":"738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6038-0795","authenticated-orcid":false,"given":"Anissa Rym","family":"Saidia","sequence":"first","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Ruel","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, 34295 Montpellier, France"},{"name":"Cognitive Neuroscience Laboratory, Aix-Marseille University, CNRS, UMR 7291, 13331 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7042-4616","authenticated-orcid":false,"given":"Amel","family":"Bahloul","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5934-9774","authenticated-orcid":false,"given":"Benjamin","family":"Chaix","sequence":"additional","affiliation":[{"name":"Department of ENT and Head and Neck Surgery, University Hospital of Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Venail","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, 34295 Montpellier, France"},{"name":"Department of ENT and Head and Neck Surgery, University Hospital of Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-719X","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, 34295 Montpellier, France"},{"name":"Department of ENT and Head and Neck Surgery, University Hospital of Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/brain\/119.3.741","article-title":"Auditory Neuropathy","volume":"119","author":"Starr","year":"1996","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1093\/brain\/awg156","article-title":"Pathology and Physiology of Auditory Neuropathy with a Novel Mutation in the MPZ Gene (Tyr145->Ser)","volume":"126","author":"Starr","year":"2003","journal-title":"Brain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1001\/archotol.127.6.629","article-title":"Selective Inner Hair Cell Loss in Premature Infants and Cochlea Pathological Patterns from Neonatal Intensive Care Unit Autopsies","volume":"127","author":"Amatuzzi","year":"2001","journal-title":"Arch. Otolaryngol.-Head Neck Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3109\/01050398309076244","article-title":"Hereditary Dysfunction of the Brain Stem Auditory Pathways as the Major Cause of Speech Retardation","volume":"12","author":"Blegvad","year":"1983","journal-title":"Scand. Audiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/nrneurol.2016.10","article-title":"Auditory Neuropathy\u2014Neural and Synaptic Mechanisms","volume":"12","author":"Moser","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3389\/fneur.2017.00622","article-title":"A European Perspective on Auditory Processing Disorder-Current Knowledge and Future Research Focus","volume":"8","author":"Iliadou","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1093\/brain\/114.3.1157","article-title":"Absence of Both Auditory Evoked Potentials and Auditory Percepts Dependent on Timing Cues","volume":"114","author":"Starr","year":"1991","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/00003446-200104000-00002","article-title":"Cochlear Receptor (Microphonic and Summating Potentials, Otoacoustic Emissions) and Auditory Pathway (Auditory Brain Stem Potentials) Activity in Auditory Neuropathy","volume":"22","author":"Starr","year":"2001","journal-title":"Ear Hear."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1093\/brain\/awt056","article-title":"Loudness Adaptation Accompanying Ribbon Synapse and Auditory Nerve Disorders","volume":"136","author":"Wynne","year":"2013","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1126\/science.8160013","article-title":"Loudness-Coding Mechanisms Inferred from Electric Stimulation of the Human Auditory System","volume":"264","author":"Zeng","year":"1994","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.heares.2012.05.009","article-title":"An Active Loudness Model Suggesting Tinnitus as Increased Central Noise and Hyperacusis as Increased Nonlinear Gain","volume":"295","author":"Zeng","year":"2013","journal-title":"Hear. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"De Siati, R.D., Rosenzweig, F., Gersdorff, G., Gregoire, A., Rombaux, P., and Deggouj, N. (2020). Auditory Neuropathy Spectrum Disorders: From Diagnosis to Treatment: Literature Review and Case Reports. JCM, 9.","DOI":"10.3390\/jcm9041074"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1177\/0194599813478575","article-title":"Cochlear Implantation versus Hearing Amplification in Patients with Auditory Neuropathy Spectrum Disorder","volume":"148","author":"Pelosi","year":"2013","journal-title":"Otolaryngol.-Head Neck Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3766\/jaaa.15050","article-title":"Children with Auditory Neuropathy Spectrum Disorder Fitted with Hearing Aids Applying the American Academy of Audiology Pediatric Amplification Guideline: Current Practice and Outcomes","volume":"27","author":"Walker","year":"2016","journal-title":"J. Am. Acad. Audiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3109\/14992027.2013.786190","article-title":"Does Cochlear Implantation Improve Speech Recognition in Children with Auditory Neuropathy Spectrum Disorder? A Systematic Review","volume":"52","author":"Humphriss","year":"2013","journal-title":"Int. J. Audiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.3109\/14992027.2013.796532","article-title":"Impact of the Presence of Auditory Neuropathy Spectrum Disorder (ANSD) on Outcomes of Children at Three Years of Age","volume":"52","author":"Ching","year":"2013","journal-title":"Int. J. Audiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1093\/brain\/awu378","article-title":"OPA1-Related Auditory Neuropathy: Site of Lesion and Outcome of Cochlear Implantation","volume":"138","author":"Santarelli","year":"2015","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1044\/1059-0889(2011\/10-0032)","article-title":"Audiologic Management of Auditory Neuropathy Spectrum Disorder in Children: A Systematic Review of the Literature","volume":"20","author":"Roush","year":"2011","journal-title":"Am. J. Audiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1083\/jcb.201002089","article-title":"Otoferlin Is a Calcium Sensor That Directly Regulates SNARE-Mediated Membrane Fusion","volume":"191","author":"Johnson","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e31013","DOI":"10.7554\/eLife.31013","article-title":"Otoferlin Acts as a Ca2+ Sensor for Vesicle Fusion and Vesicle Pool Replenishment at Auditory Hair Cell Ribbon Synapses","volume":"6","author":"Michalski","year":"2017","journal-title":"Elife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.tins.2012.08.002","article-title":"Otoferlin: A Multi-C2 Domain Protein Essential for Hearing","volume":"35","author":"Reisinger","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/7693","article-title":"A Mutation in OTOF, Encoding Otoferlin, a FER-1-like Protein, Causes DFNB9, a Nonsyndromic Form of Deafness","volume":"21","author":"Yasunaga","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107906","DOI":"10.1016\/j.heares.2020.107906","article-title":"Small Fish, Big Prospects: Using Zebrafish to Unravel the Mechanisms of Hereditary Hearing Loss","volume":"397","author":"Vona","year":"2020","journal-title":"Hear. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.heares.2015.07.007","article-title":"Audibility, Speech Perception and Processing of Temporal Cues in Ribbon Synaptic Disorders Due to OTOF Mutations","volume":"330","author":"Santarelli","year":"2015","journal-title":"Hear. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1399-0004.2008.01128.x","article-title":"Identities and Frequencies of Mutations of the Otoferlin Gene (OTOF) Causing DFNB9 Deafness in Pakistan","volume":"75","author":"Choi","year":"2009","journal-title":"Clin. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/humu.20708","article-title":"A Multicenter Study on the Prevalence and Spectrum of Mutations in the Otoferlin Gene (OTOF) in Subjects with Nonsyndromic Hearing Impairment and Auditory Neuropathy","volume":"29","author":"Reynoso","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1136\/jmg.2005.038612","article-title":"OTOF Mutations Revealed by Genetic Analysis of Hearing Loss Families Including a Potential Temperature Sensitive Auditory Neuropathy Allele","volume":"43","author":"Varga","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"639","DOI":"10.3390\/audiolres11040059","article-title":"Electrocochleography in Auditory Neuropathy Related to Mutations in the OTOF or OPA1 Gene","volume":"11","author":"Santarelli","year":"2021","journal-title":"Audiol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/nn.2578","article-title":"Hearing Requires Otoferlin-Dependent Efficient Replenishment of Synaptic Vesicles in Hair Cells","volume":"13","author":"Pangrsic","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.cell.2006.08.040","article-title":"Otoferlin, Defective in a Human Deafness Form, Is Essential for Exocytosis at the Auditory Ribbon Synapse","volume":"127","author":"Roux","year":"2006","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrn2969","article-title":"From Glutamate Co-Release to Vesicular Synergy: Vesicular Glutamate Transporters","volume":"12","author":"Fortin","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2010.12.040","article-title":"The Vesicular Glutamate Transporter-1 Upstream Promoter and First Intron Each Support Glutamatergic-Specific Expression in Rat Postrhinal Cortex","volume":"1377","author":"Zhang","year":"2011","journal-title":"Brain Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ajhg.2008.07.008","article-title":"Impairment of SLC17A8 Encoding Vesicular Glutamate Transporter-3, VGLUT3, Underlies Nonsyndromic Deafness DFNA25 and Inner Hair Cell Dysfunction in Null Mice","volume":"83","author":"Ruel","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.neuron.2007.11.032","article-title":"Sensorineural Deafness and Seizures in Mice Lacking Vesicular Glutamate Transporter 3","volume":"57","author":"Seal","year":"2008","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1523\/JNEUROSCI.0619-20.2021","article-title":"Outer Hair Cell Glutamate Signaling through Type II Spiral Ganglion Afferents Activates Neurons in the Cochlear Nucleus in Response to Nondamaging Sounds","volume":"41","author":"Weisz","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.neuron.2012.05.019","article-title":"Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy","volume":"75","author":"Akil","year":"2012","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1523\/JNEUROSCI.2228-18.2019","article-title":"Vesicular Glutamatergic Transmission in Noise-Induced Loss and Repair of Cochlear Ribbon Synapses","volume":"39","author":"Kim","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/ajmg.a.10155","article-title":"Molecular Characterization of a 12q22-Q24 Deletion Associated with Congenital Deafness: Confirmation and Refinement of the DFNA25 Locus","volume":"117","author":"Petek","year":"2003","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ryu, N., Sagong, B., Park, H.-J., Kim, M.-A., Lee, K.-Y., Choi, J.Y., and Kim, U.-K. (2016). Screening of the SLC17A8 Gene as a Causative Factor for Autosomal Dominant Non-Syndromic Hearing Loss in Koreans. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0269-3"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1113\/JP282181","article-title":"VGLUT3-p.A211V Variant Fuses Stereocilia Bundles and Elongates Synaptic Ribbons","volume":"599","author":"Joshi","year":"2021","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10832","DOI":"10.1523\/JNEUROSCI.23-34-10832.2003","article-title":"CaV1.3 Channels Are Essential for Development and Presynaptic Activity of Cochlear Inner Hair Cells","volume":"23","author":"Brandt","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nn.2694","article-title":"Loss of Ca(v)1.3 (CACNA1D) Function in a Human Channelopathy with Bradycardia and Congenital Deafness","volume":"14","author":"Baig","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0092-8674(00)00013-1","article-title":"Congenital Deafness and Sinoatrial Node Dysfunction in Mice Lacking Class D L-Type Ca2+ Channels","volume":"102","author":"Platzer","year":"2000","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6490","DOI":"10.18632\/aging.102203","article-title":"Down-Regulation of Cav1.3 in Auditory Pathway Promotes Age-Related Hearing Loss by Enhancing Calcium-Mediated Oxidative Stress in Male Mice","volume":"11","author":"Qi","year":"2019","journal-title":"Aging"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3389\/fncel.2019.00225","article-title":"Cochlea-Specific Deletion of Cav1.3 Calcium Channels Arrests Inner Hair Cell Differentiation and Unravels Pitfalls of Conditional Mouse Models","volume":"13","author":"Eckrich","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1006\/bbrc.2001.6228","article-title":"Calcium-Binding Proteins: Intracellular Sensors from the Calmodulin Superfamily","volume":"290","author":"Haeseleer","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.bbagen.2011.12.012","article-title":"Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels","volume":"1820","author":"Christel","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/j.1399-0004.2010.01593.x","article-title":"DFNB93, a Novel Locus for Autosomal Recessive Moderate-to-Severe Hearing Impairment","volume":"79","author":"Tabatabaiefar","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ajhg.2012.08.018","article-title":"A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-Recessive Hearing Impairment","volume":"91","author":"Schrauwen","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/gim.2015.89","article-title":"Comprehensive Analysis via Exome Sequencing Uncovers Genetic Etiology in Autosomal Recessive Nonsyndromic Deafness in a Large Multiethnic Cohort","volume":"18","author":"Bademci","year":"2016","journal-title":"Genet. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"689415","DOI":"10.3389\/fnmol.2021.689415","article-title":"Cabp2-Gene Therapy Restores Inner Hair Cell Calcium Currents and Improves Hearing in a DFNB93 Mouse Model","volume":"14","author":"Oestreicher","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E1717","DOI":"10.1073\/pnas.1617533114","article-title":"Ca2+-Binding Protein 2 Inhibits Ca2+-Channel Inactivation in Mouse Inner Hair Cells","volume":"114","author":"Picher","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.heares.2018.04.001","article-title":"Functions of CaBP1 and CaBP2 in the Peripheral Auditory System","volume":"364","author":"Yang","year":"2018","journal-title":"Hear. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Schoen, C.J., Burmeister, M., and Lesperance, M.M. (2013). Diaphanous Homolog 3 (Diap3) Overexpression Causes Progressive Hearing Loss and Inner Hair Cell Defects in a Transgenic Mouse Model of Human Deafness. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056520"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1093\/brain\/awv270","article-title":"Pathophysiological Mechanisms and Functional Hearing Consequences of Auditory Neuropathy","volume":"138","author":"Rance","year":"2015","journal-title":"Brain"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Surel, C., Guillet, M., Lenoir, M., Bourien, J., Sendin, G., Joly, W., Delprat, B., Lesperance, M.M., Puel, J.-L., and Nouvian, R. (2016). Remodeling of the Inner Hair Cell Microtubule Meshwork in a Mouse Model of Auditory Neuropathy AUNA1. eNeuro, 3.","DOI":"10.1523\/ENEURO.0295-16.2016"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ijporl.2010.11.023","article-title":"The Genetic Basis of Auditory Neuropathy Spectrum Disorder (ANSD)","volume":"75","author":"Manchaiah","year":"2011","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/ajmg.a.33970","article-title":"Identification of p.A684V Missense Mutation in the WFS1 Gene as a Frequent Cause of Autosomal Dominant Optic Atrophy and Hearing Impairment","volume":"155","author":"Rendtorff","year":"2011","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1007\/s00415-018-8884-x","article-title":"Auditory Function in Pelizaeus-Merzbacher Disease","volume":"265","author":"Morlet","year":"2018","journal-title":"J. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16504","DOI":"10.1038\/s41598-017-16676-9","article-title":"ATP1A3 Mutations Can Cause Progressive Auditory Neuropathy: A New Gene of Auditory Synaptopathy","volume":"7","author":"Han","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0092-8674(91)90613-4","article-title":"DNA Duplication Associated with Charcot-Marie-Tooth Disease Type 1A","volume":"66","author":"Lupski","year":"1991","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1093\/brain\/aws085","article-title":"Auditory Function in Children with Charcot-Marie-Tooth Disease","volume":"135","author":"Rance","year":"2012","journal-title":"Brain"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3109\/00016488709134697","article-title":"Auditory Function in Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)","volume":"103","author":"Raglan","year":"1987","journal-title":"Acta Oto-Laryngol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/ajmg.10223","article-title":"Anticipation in a Unique Family with Charcot-Marie-Tooth Syndrome and Deafness: Delineation of the Clinical Features and Review of the Literature","volume":"108","author":"Kovach","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10335","DOI":"10.1038\/s41598-018-28501-y","article-title":"Hidden Hearing Loss in Patients with Charcot-Marie-Tooth Disease Type 1A","volume":"8","author":"Choi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/0002-9394(79)90565-8","article-title":"A Clinicopathologic Study of Autosomal Dominant Optic Atrophy","volume":"88","author":"Johnston","year":"1979","journal-title":"Am. J. Ophthalmol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/79944","article-title":"OPA1, Encoding a Dynamin-Related GTPase, Is Mutated in Autosomal Dominant Optic Atrophy Linked to Chromosome 3q28","volume":"26","author":"Alexander","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/79936","article-title":"Nuclear Gene OPA1, Encoding a Mitochondrial Dynamin-Related Protein, Is Mutated in Dominant Optic Atrophy","volume":"26","author":"Delettre","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"100935","DOI":"10.1016\/j.preteyeres.2020.100935","article-title":"Dominant Optic Atrophy: Culprit Mitochondria in the Optic Nerve","volume":"83","author":"Lenaers","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/ana.20681","article-title":"OPA1 R445H Mutation in Optic Atrophy Associated with Sensorineural Deafness","volume":"58","author":"Guichet","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ana.20278","article-title":"Deficit of in Vivo Mitochondrial ATP Production in OPA1-Related Dominant Optic Atrophy","volume":"56","author":"Lodi","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7743","DOI":"10.1074\/jbc.C200677200","article-title":"Loss of OPA1 Perturbates the Mitochondrial Inner Membrane Structure and Integrity, Leading to Cytochrome c Release and Apoptosis","volume":"278","author":"Olichon","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cell.2006.06.025","article-title":"OPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial Fusion","volume":"126","author":"Frezza","year":"2006","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/brain\/awm298","article-title":"OPA1 Mutations Induce Mitochondrial DNA Instability and Optic Atrophy \u201cplus\u201d Phenotypes","volume":"131","author":"Valentino","year":"2008","journal-title":"Brain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.bbamcr.2012.08.004","article-title":"The Dynamin GTPase OPA1: More than Mitochondria?","volume":"1833","author":"Belenguer","year":"2013","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1101\/gr.108696.110","article-title":"OPA1 Links Human Mitochondrial Genome Maintenance to MtDNA Replication and Distribution","volume":"21","author":"Elachouri","year":"2011","journal-title":"Genome Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.preteyeres.2003.10.003","article-title":"Mitochondrial Dysfunction as a Cause of Optic Neuropathies","volume":"23","author":"Carelli","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1212\/WNL.0b013e318230a15a","article-title":"Subclinical Multisystem Neurologic Disease in \u201cPure\u201d OPA1 Autosomal Dominant Optic Atrophy","volume":"77","author":"Baker","year":"2011","journal-title":"Neurology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/brain\/awq007","article-title":"Multi-System Neurological Disease Is Common in Patients with OPA1 Mutations","volume":"133","author":"Griffiths","year":"2010","journal-title":"Brain"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e236","DOI":"10.1093\/brain\/aws340","article-title":"Sensorineural Hearing Loss in OPA1-Linked Disorders","volume":"136","author":"Leruez","year":"2013","journal-title":"Brain"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e225","DOI":"10.1111\/aos.12038","article-title":"Novel OPA1 Missense Mutation in a Family with Optic Atrophy and Severe Widespread Neurological Disorder","volume":"91","author":"Liskova","year":"2013","journal-title":"Acta Ophthalmol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1750-1172-7-46","article-title":"Dominant Optic Atrophy","volume":"7","author":"Lenaers","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.brainres.2009.08.083","article-title":"Mutation of OPA1 Gene Causes Deafness by Affecting Function of Auditory Nerve Terminals","volume":"1300","author":"Huang","year":"2009","journal-title":"Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/gm212","article-title":"Information from Cochlear Potentials and Genetic Mutations Helps Localize the Lesion Site in Auditory Neuropathy","volume":"2","author":"Santarelli","year":"2010","journal-title":"Genome Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/brain\/89.1.15","article-title":"Further Clinical and Pathological Observations on Leber\u2019s Optic Atrophy","volume":"89","author":"Adams","year":"1966","journal-title":"Brain"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1136\/jnnp.2003.017673","article-title":"Progressive Auditory Neuropathy in Patients with Leber\u2019s Hereditary Optic Neuropathy","volume":"75","author":"Luxon","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_87","first-page":"650","article-title":"Nonsense Mutation in TMEM126A Causing Autosomal Recessive Optic Atrophy and Auditory Neuropathy","volume":"16","author":"Meyer","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJM199610173351601","article-title":"Clinical and Genetic Abnormalities in Patients with Friedreich\u2019s Ataxia","volume":"335","author":"Cossee","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich\u2019s Ataxia: A Clinical and Genetic Study of 90 Families with an Analysis of Early Diagnostic Criteria and Intrafamilial Clustering of Clinical Features","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1001\/archneur.59.5.743","article-title":"Friedreich Ataxia: Effects of Genetic Understanding on Clinical Evaluation and Therapy","volume":"59","author":"Lynch","year":"2002","journal-title":"Arch. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/mao.0b013e31815e92fd","article-title":"Speech Perception in Children with Auditory Neuropathy\/Dyssynchrony Managed with Either Hearing AIDS or Cochlear Implants","volume":"29","author":"Rance","year":"2008","journal-title":"Otol. Neurotol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000255341","article-title":"Auditory Perception in Individuals with Friedreich\u2019s Ataxia","volume":"15","author":"Rance","year":"2010","journal-title":"Audiol. Neurotol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1212\/WNL.33.8.1071","article-title":"Early Abnormalities of Brainstem Auditory Evoked Potentials in Friedreich\u2019s Ataxia: Evidence of Primary Brainstem Dysfunction","volume":"33","author":"Jabbari","year":"1983","journal-title":"Neurology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1159\/000375307","article-title":"Abnormal Cochlear Potentials in Friedreich\u2019s Ataxia Point to Disordered Synchrony of Auditory Nerve Fiber Activity","volume":"15","author":"Santarelli","year":"2015","journal-title":"Neurodegener. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s12311-021-01236-9","article-title":"Auditory Phenotypic Variability in Friedreich\u2019s Ataxia Patients","volume":"20","author":"Koohi","year":"2021","journal-title":"Cerebellum"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1097\/MLG.0b013e3180581944","article-title":"Otopathology in Mohr-Tranebj\u00e6rg Syndrome","volume":"117","author":"Bahmad","year":"2007","journal-title":"Laryngoscope"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1126\/science.8493530","article-title":"The Basic Science of Gene Therapy","volume":"260","author":"Mulligan","year":"1993","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/gt.2012.51","article-title":"Gene Transfer in Inner Ear Cells: A Challenging Race","volume":"20","author":"Sacheli","year":"2013","journal-title":"Gene Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1152\/physrev.00053.2017","article-title":"Toward Cochlear Therapies","volume":"98","author":"Wang","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.1523\/JNEUROSCI.5122-10.2011","article-title":"Probing the Functional Equivalence of Otoferlin and Synaptotagmin 1 in Exocytosis","volume":"31","author":"Reisinger","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"13281","DOI":"10.1523\/JNEUROSCI.2528-10.2010","article-title":"Control of Exocytosis by Synaptotagmins and Otoferlin in Auditory Hair Cells","volume":"30","author":"Beurg","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1046\/j.1460-9568.1999.00487.x","article-title":"SNARE Complex at the Ribbon Synapses of Cochlear Hair Cells: Analysis of Synaptic Vesicle- and Synaptic Membrane-Associated Proteins","volume":"11","author":"Safieddine","year":"1999","journal-title":"Eur. J. Neurosci."},{"key":"ref_103","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":"ref_104","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1089\/hum.2010.122","article-title":"Efficient Transgene Reconstitution with Hybrid Dual AAV Vectors Carrying the Minimized Bridging Sequences","volume":"22","author":"Ghosh","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"600051","DOI":"10.3389\/fnmol.2020.600051","article-title":"Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness","volume":"13","author":"Rankovic","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1089\/hum.2022.062","article-title":"Gene Therapy Restores Auditory Functions in an Adult Vglut3 Knockout Mouse Model","volume":"33","author":"Zhao","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ng0692-166","article-title":"The Peripheral Myelin Gene PMP-22\/GAS-3 Is Duplicated in Charcot-Marie-Tooth Disease Type 1A","volume":"1","author":"Valentijn","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng0692-171","article-title":"The Peripheral Myelin Protein Gene PMP-22 Is Contained within the Charcot-Marie-Tooth Disease Type 1A Duplication","volume":"1","author":"Timmerman","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ng0692-176","article-title":"Peripheral Myelin Protein-22 Gene Maps in the Duplication in Chromosome 17p11.2 Associated with Charcot-Marie-Tooth 1A","volume":"1","author":"Matsunami","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.nbd.2017.01.006","article-title":"Pmp22 Mutant Allele-Specific SiRNA Alleviates Demyelinating Neuropathic Phenotype in Vivo","volume":"100","author":"Lee","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1038\/s41467-021-22593-3","article-title":"AAV2\/9-Mediated Silencing of PMP22 Prevents the Development of Pathological Features in a Rat Model of Charcot-Marie-Tooth Disease 1\u2009A","volume":"12","author":"Gautier","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"279","DOI":"10.5607\/en.2019.28.2.279","article-title":"MiR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22","volume":"28","author":"Lee","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s42003-021-01839-2","article-title":"Squalenoyl SiRNA PMP22 Nanoparticles Are Effective in Treating Mouse Models of Charcot-Marie-Tooth Disease Type 1 A","volume":"4","author":"Boutary","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41434-019-0098-z","article-title":"Downregulation of the Human Peripheral Myelin Protein 22 Gene by MiR-29a in Cellular Models of Charcot-Marie-Tooth Disease","volume":"26","author":"Serfecz","year":"2019","journal-title":"Gene Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1172\/JCI96499","article-title":"PMP22 Antisense Oligonucleotides Reverse Charcot-Marie-Tooth Disease Type 1A Features in Rodent Models","volume":"128","author":"Zhao","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_116","first-page":"130","article-title":"Targeted PMP22 TATA-Box Editing by CRISPR\/Cas9 Reduces Demyelinating Neuropathy of Charcot-Marie-Tooth Disease Type 1A in Mice","volume":"48","author":"Lee","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/wrna.1347","article-title":"MRNA Trans-Splicing in Gene Therapy for Genetic Diseases","volume":"7","author":"Berger","year":"2016","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"146533","DOI":"10.1016\/j.brainres.2019.146533","article-title":"Gene Therapy to Promote Regeneration in Charcot-Marie-Tooth Disease","volume":"1727","author":"Sahenk","year":"2020","journal-title":"Brain Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1212\/01.WNL.0000171978.70849.c5","article-title":"NT-3 Promotes Nerve Regeneration and Sensory Improvement in CMT1A Mouse Models and in Patients","volume":"65","author":"Sahenk","year":"2005","journal-title":"Neurology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/mt.2013.250","article-title":"AAV1.NT-3 Gene Therapy for Charcot-Marie-Tooth Neuropathy","volume":"22","author":"Sahenk","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1136\/jmg.39.8.e47","article-title":"Deletion of the OPA1 Gene in a Dominant Optic Atrophy Family: Evidence That Haploinsufficiency Is the Cause of Disease","volume":"39","author":"Marchbank","year":"2002","journal-title":"J. Med. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1038\/s41598-018-20838-8","article-title":"OPA1 Gene Therapy Prevents Retinal Ganglion Cell Loss in a Dominant Optic Atrophy Mouse Model","volume":"8","author":"Sarzi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.omtn.2021.10.019","article-title":"Autosomal Dominant Optic Atrophy: A Novel Treatment for OPA1 Splice Defects Using U1 SnRNA Adaption","volume":"26","author":"Klopstock","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.omtn.2021.08.015","article-title":"CRISPR-Cas9 Correction of OPA1 c.1334G>A: P.R445H Restores Mitochondrial Homeostasis in Dominant Optic Atrophy Patient-Derived IPSCs","volume":"26","author":"Sladen","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/IIO.0000000000000364","article-title":"Gene Therapies for the Treatment of Leber Hereditary Optic Neuropathy","volume":"61","author":"Sahel","year":"2021","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"651639","DOI":"10.3389\/fneur.2021.651639","article-title":"Leber Hereditary Optic Neuropathy: Review of Treatment and Management","volume":"12","author":"Hage","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ajhg.2008.08.013","article-title":"Optimized Allotopic Expression of the Human Mitochondrial ND4 Prevents Blindness in a Rat Model of Mitochondrial Dysfunction","volume":"83","author":"Ellouze","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Marella, M., Seo, B.B., Thomas, B.B., Matsuno-Yagi, A., and Yagi, T. (2010). Successful Amelioration of Mitochondrial Optic Neuropathy Using the Yeast NDI1 Gene in a Rat Animal Model. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011472"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1111\/j.1442-9071.2012.02815.x","article-title":"Adeno-Associated Virus-Mediated Gene Delivery of the Human ND4 Complex I Subunit in Rabbit Eyes","volume":"40","author":"Shi","year":"2012","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"E1238","DOI":"10.1073\/pnas.1119577109","article-title":"Gene Delivery to Mitochondria by Targeting Modified Adenoassociated Virus Suppresses Leber\u2019s Hereditary Optic Neuropathy in a Mouse Model","volume":"109","author":"Yu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ejhg.2012.112","article-title":"Intravitreal Delivery of AAV-NDI1 Provides Functional Benefit in a Murine Model of Leber Hereditary Optic Neuropathy","volume":"21","author":"Chadderton","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1001\/jamaophthalmol.2013.7630","article-title":"Safety and Effects of the Vector for the Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial","volume":"132","author":"Koilkonda","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7739","DOI":"10.1167\/iovs.14-15388","article-title":"LHON Gene Therapy Vector Prevents Visual Loss and Optic Neuropathy Induced by G11778A Mutant Mitochondrial DNA: Biodistribution and Toxicology Profile","volume":"55","author":"Koilkonda","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","article-title":"Development and Applications of CRISPR-Cas9 for Genome Engineering","volume":"157","author":"Hsu","year":"2014","journal-title":"Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature25164","article-title":"Treatment of Autosomal Dominant Hearing Loss by in Vivo Delivery of Genome Editing Agents","volume":"553","author":"Gao","year":"2018","journal-title":"Nature"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1089\/hum.2008.107","article-title":"Treatment of Leber Congenital Amaurosis Due to RPE65 Mutations by Ocular Subretinal Injection of Adeno-Associated Virus Gene Vector: Short-Term Results of a Phase I Trial","volume":"19","author":"Hauswirth","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1056\/NEJMoa0802268","article-title":"Effect of Gene Therapy on Visual Function in Leber\u2019s Congenital Amaurosis","volume":"358","author":"Bainbridge","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"15112","DOI":"10.1073\/pnas.0807027105","article-title":"Human Gene Therapy for RPE65 Isomerase Deficiency Activates the Retinoid Cycle of Vision but with Slow Rod Kinetics","volume":"105","author":"Cideciyan","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-Associated Virus Vector as a Platform for Gene Therapy Delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_140","unstructured":"HHTM (2022, November 30). Decibel Therapeutics Announces Submission of Clinical Trial Applications for Lead Gene Therapy Candidate DB-OTO\u2013HHTM. Available online: https:\/\/hearinghealthmatters.org\/hearingnewswatch\/2022\/decibel-therapeutics-clinical-trial-submission\/."},{"key":"ref_141","unstructured":"(2022, November 30). Sensorion Receives US FDA Rare Pediatric Disease Designation for Gene Therapy. Available online: https:\/\/www.biopharma-reporter.com\/Article\/2022\/11\/07\/sensorion-receives-us-fda-rare-pediatric-disease-designation-for-gene-therapy."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/3\/738\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:08:05Z","timestamp":1760119685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/3\/738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":141,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12030738"],"URL":"https:\/\/doi.org\/10.3390\/jcm12030738","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]}}}