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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Mutations in SLC26A4, which encodes the anion transporter pendrin, represent one of the most common genetic causes of hereditary hearing loss, including Pendred syndrome and DFNB4. Pendrin plays a critical role in maintaining ion homeostasis within the inner ear, particularly in the endolymphatic sac (ES), making it an important therapeutic target for gene replacement strategies. However, efficient delivery of therapeutic genes to relevant inner ear structures remains a major challenge for clinical translation. In this study, we evaluated the inner ear transduction profile of AAV8BP2, an engineered AAV8-derived capsid, in comparison with AAV2.7m8 and AAV8 in mice. Neonatal mice received posterior semicircular canal (PSCC) injections at postnatal day 0 (P0), and viral transduction in the cochlea and ES was assessed at P7. To examine age-dependent differences in viral transduction, additional experiments were performed in adult mice injected at P21 and analyzed at P28. We also compared three surgical delivery routes for inner ear gene transfer: PSCC injection, round window membrane (RWM) injection, and RWM injection combined with PSCC fenestration. AAV8BP2 effectively transduced the ES in both neonatal and adult mice and showed greater GFP expression in the spiral prominence than AAV8 following neonatal administration. Among the three delivery routes evaluated in adult mice, PSCC injection achieved the highest ES transduction while maintaining cochlear hair cell transduction comparable to that achieved with RWM-based approaches. Together, these findings define the relative transduction profiles of the tested AAV capsids and delivery routes and provide a basis for selecting vector-delivery route combinations for SLC26A4-targeted inner ear gene therapy.<\/jats:p>","DOI":"10.3390\/ijms27177884","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:13:25Z","timestamp":1788455605000},"page":"7884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficient Endolymphatic Sac-Directed Gene Delivery Using AAV8BP2 and Posterior Semicircular Canal Injection"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-5812","authenticated-orcid":false,"given":"Minjin","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Won-Sang Lee Institute for Hearing Loss, Yonsei University, Seoul 03722, Republic of Korea"},{"name":"Bio-Centennial Convergence Institute, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-7671","authenticated-orcid":false,"given":"Michelle J.","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Jeju National University Hospital, Jeju 63241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-6177","authenticated-orcid":false,"given":"Heon Yung","family":"Gee","sequence":"additional","affiliation":[{"name":"Won-Sang Lee Institute for Hearing Loss, Yonsei University, Seoul 03722, Republic of Korea"},{"name":"Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Wade W.","family":"Chien","sequence":"additional","affiliation":[{"name":"Section on Inner Ear Therapeutics, Neurotology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-6969","authenticated-orcid":false,"given":"Jinsei","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Won-Sang Lee Institute for Hearing Loss, Yonsei University, Seoul 03722, Republic of Korea"},{"name":"Bio-Centennial Convergence Institute, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/S0140-6736(21)00516-X","article-title":"Hearing loss prevalence and years lived with disability, 1990\u20132019: Findings from the Global Burden of Disease Study 2019","volume":"397","author":"Haile","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1016\/S2214-109X(23)00514-4","article-title":"Priorities for hearing loss prevention and estimates of global cause-specific burdens of hearing loss: A systematic rapid review","volume":"12","author":"Prasad","year":"2024","journal-title":"Lancet Glob. Health"},{"key":"ref_3","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). Genetic Hearing Loss Overview. GeneReviews((R)), University of Washington."},{"key":"ref_4","unstructured":"Walls, W.D., and Smith, A.H. (2026, August 20). Hereditary Hearing Loss Homepage. Available online: https:\/\/hereditaryhearingloss.org."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lee, N.K., Uhler, K.M., Yoon, P.J., and Santos-Cortez, R.L.P. (2024). Clinical Genetic Testing for Hearing Loss: Implications for Genetic Counseling and Gene-Based Therapies. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071427"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s41576-023-00597-7","article-title":"Deafness: From genetic architecture to gene therapy","volume":"24","author":"Petit","year":"2023","journal-title":"Nat. Rev. Genet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/ng1297-411","article-title":"Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS)","volume":"17","author":"Everett","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00439-021-02311-1","article-title":"Genetic architecture and phenotypic landscape of SLC26A4-related hearing loss","volume":"141","author":"Honda","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tawalbeh, M., Aburizeg, D., Abu Alragheb, B.O., Alaqrabawi, W.S., Dardas, Z., Srour, L., Altarayra, B.H., Zayed, A.A., El Omari, Z., and Azab, B. (2022). SLC26A4 Phenotypic Variability Influences Intra- and Inter-Familial Diagnosis and Management. Genes, 13.","DOI":"10.3390\/genes13122192"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1159\/000335113","article-title":"The role of pendrin in the development of the murine inner ear","volume":"28","author":"Wangemann","year":"2011","journal-title":"Cell Physiol. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wangemann, P., Itza, E.M., Albrecht, B., Wu, T., Jabba, S.V., Maganti, R.J., Lee, J.H., Everett, L.A., Wall, S.M., and Royaux, I.E. (2004). Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model. BMC Med., 2.","DOI":"10.1186\/1741-7015-2-30"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s10162-002-3052-4","article-title":"Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome","volume":"4","author":"Royaux","year":"2003","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3390\/audiolres11030040","article-title":"Genetic Determinants of Non-Syndromic Enlarged Vestibular Aqueduct: A Review","volume":"11","author":"Roesch","year":"2021","journal-title":"Audiol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.celrep.2016.12.020","article-title":"Cochlear Cell Modeling Using Disease-Specific iPSCs Unveils a Degenerative Phenotype and Suggests Treatments for Congenital Progressive Hearing Loss","volume":"18","author":"Hosoya","year":"2017","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41467-023-44612-1","article-title":"Mechanism of anion exchange and small-molecule inhibition of pendrin","volume":"15","author":"Wang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00439-021-02336-6","article-title":"Exploring the missing heritability in subjects with hearing loss, enlarged vestibular aqueducts, and a single or no pathogenic SLC26A4 variant","volume":"141","author":"Smits","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"115445","DOI":"10.1016\/j.biopha.2023.115445","article-title":"Novel small molecule-mediated restoration of the surface expression and anion exchange activity of mutated pendrin causing Pendred syndrome and DFNB4","volume":"167","author":"Jung","year":"2023","journal-title":"BioMed Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7184","DOI":"10.7150\/thno.38032","article-title":"Gene therapy for hereditary hearing loss by SLC26A4 mutations in mice reveals distinct functional roles of pendrin in normal hearing","volume":"9","author":"Kim","year":"2019","journal-title":"Theranostics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e193812","DOI":"10.1172\/JCI193812","article-title":"Postnatal Slc26a4 gene therapy improves hearing and structural integrity in a hereditary hearing loss model","volume":"136","author":"Tsai","year":"2026","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.ymthe.2023.02.001","article-title":"Advances in gene therapy hold promise for treating hereditary hearing loss","volume":"31","author":"Jiang","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109151","DOI":"10.1016\/j.heares.2024.109151","article-title":"Gene therapy for hereditary hearing loss","volume":"455","author":"Fu","year":"2025","journal-title":"Hear Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40259-017-0234-5","article-title":"Adeno-Associated Virus (AAV) as a Vector for Gene Therapy","volume":"31","author":"Naso","year":"2017","journal-title":"BioDrugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1016\/j.ymthe.2022.09.015","article-title":"AAV vectors: The Rubik\u2019s cube of human gene therapy","volume":"30","author":"Pupo","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112265","DOI":"10.1016\/j.isci.2025.112265","article-title":"The clinical safety landscape for ocular AAV gene therapies: A systematic review and meta-analysis","volume":"28","author":"Liu","year":"2025","journal-title":"iScience"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/d41573-021-00017-7","article-title":"The clinical landscape for AAV gene therapies","volume":"20","author":"Kuzmin","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno-associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"189ra176","DOI":"10.1126\/scitranslmed.3005708","article-title":"In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous","volume":"5","author":"Dalkara","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107947","DOI":"10.1016\/j.heares.2020.107947","article-title":"Adeno-associated virus gene replacement for recessive inner ear dysfunction: Progress and challenges","volume":"394","author":"Askew","year":"2020","journal-title":"Hear Res."},{"key":"ref_29","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":"ref_30","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.15252\/emmm.201404077","article-title":"Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter","volume":"6","author":"Cronin","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.omtm.2022.07.013","article-title":"AAV8BP2 and AAV8 transduce the mammalian cochlear lateral wall and endolymphatic sac with high efficiency","volume":"26","author":"Isgrig","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3390\/audiolres13060083","article-title":"Gene Therapy for Inherited Hearing Loss: Updates and Remaining Challenges","volume":"13","author":"Hahn","year":"2023","journal-title":"Audiol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Zhang, L., Wang, D., Chen, B., and Shu, Y. (2022). Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models. Biomolecules, 13.","DOI":"10.3390\/biom13010038"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2402166","DOI":"10.1002\/advs.202402166","article-title":"AAV-mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives","volume":"11","author":"Zhang","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Honda, K., Kajino, A., and Tsutsumi, T. (2025). Comparative genomic profiling of SLC26A4-expressing cells in the inner ear and other organs. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0318972"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neuroscience.2016.04.042","article-title":"Slc26a4 expression prevents fluctuation of hearing in a mouse model of large vestibular aqueduct syndrome","volume":"329","author":"Nishio","year":"2016","journal-title":"Neuroscience"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, X., Sanneman, J.D., Harbidge, D.G., Zhou, F., Ito, T., Nelson, R., Picard, N., Chambrey, R., Eladari, D., and Miesner, T. (2013). SLC26A4 targeted to the endolymphatic sac rescues hearing and balance in Slc26a4 mutant mice. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003641"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"45524","DOI":"10.1038\/srep45524","article-title":"Cochlear gene therapy with ancestral AAV in adult mice: Complete transduction of inner hair cells without cochlear dysfunction","volume":"7","author":"Suzuki","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1038\/s41598-018-21233-z","article-title":"Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation","volume":"8","author":"Yoshimura","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1080\/00016489.2019.1654130","article-title":"Canalostomy is an ideal surgery route for inner ear gene delivery in big animal model","volume":"139","author":"Ji","year":"2019","journal-title":"Acta Otolaryngol."},{"key":"ref_41","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":"Gyorgy","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/s41467-020-20808-7","article-title":"Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42","DOI":"10.25259\/SNI_1168_2022","article-title":"Endolymphatic sac: A surreptitious anatomy for neurosurgeons","volume":"14","author":"Mohammad","year":"2023","journal-title":"Surg. Neurol. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ymthe.2025.10.005","article-title":"Gene supplementation with precise transgene expression rescues hearing loss in a mouse model with an Mpzl2 East Asian founder variant","volume":"34","author":"Jang","year":"2026","journal-title":"Mol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6449","DOI":"10.1016\/j.ymthe.2025.08.049","article-title":"Engineered virus-like particles for in vivo gene editing ameliorate hearing loss in murine DFNA2 model","volume":"33","author":"Noh","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.7150\/thno.67781","article-title":"In vivo outer hair cell gene editing ameliorates progressive hearing loss in dominant-negative Kcnq4 murine model","volume":"12","author":"Noh","year":"2022","journal-title":"Theranostics"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bae, S.H., Ikezono, T., Park, H.R., Kim, H., Matsumura, T., Saito, S., Maeda, Y., Matsuda, H., and Jung, J. (2025). Secretion of cochlin-tomoprotein (LCCL) in the middle ear following acute tympanic injury: Implications for perilymph fistula diagnosis. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1527311"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"109352","DOI":"10.1016\/j.heares.2025.109352","article-title":"Monocyte-dependent innate immunity prevents severe complications of acute bacterial infection in the middle ear in a murine model","volume":"465","author":"Bae","year":"2025","journal-title":"Hear Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:00:58Z","timestamp":1788584458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":48,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177884"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177884","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}