Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models
Inner ear gene therapy using adeno-associated viral vectors (AAVs) in neonatal mice can alleviate hearing loss in mouse models of deafness. However, efficient and safe transgene delivery to the adult mouse cochlea is critical for the effectiveness of AAV-mediated therapy. Here, we examined three gen...
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MDPI AG
2022-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/1/38 |
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| author | Yu Zhao Longlong Zhang Daqi Wang Bing Chen Yilai Shu |
| author_facet | Yu Zhao Longlong Zhang Daqi Wang Bing Chen Yilai Shu |
| author_sort | Yu Zhao |
| collection | DOAJ |
| description | Inner ear gene therapy using adeno-associated viral vectors (AAVs) in neonatal mice can alleviate hearing loss in mouse models of deafness. However, efficient and safe transgene delivery to the adult mouse cochlea is critical for the effectiveness of AAV-mediated therapy. Here, we examined three gene delivery approaches including posterior semicircular canal (PSCC) canalostomy, round window membrane (RWM) injection, and tubing-RWM+PSCC (t-RP) in adult mice. Transduction rates and survival rates of cochlear hair cells were analyzed, hearing function was recorded, AAV distribution in the sagittal brain sections was evaluated, and cochlear histopathologic images were appraised. We found that an injection volume of 1 μL AAV through the PSCC is safe and highly efficient and does not impair hearing function in adult mice, but local injection allows AAV vectors to spread slightly into the brain. We then tested five AAV serotypes (PHP.eB, IE, Anc80L65, AAV2, and PHP.s) in parallel and observed the most robust eGFP expression in inner hair cells, outer hair cells, and spiral ganglion neurons throughout the cochlea after AAV-Anc80L65 injection. Thus, PSCC-injected Anc80L65 provides a foundation for gene therapy in the adult cochlea and will facilitate the development of inner ear gene therapy. |
| first_indexed | 2024-03-09T13:27:36Z |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T13:27:36Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-c3f2d44a98994e7d9101f3840bd2e74b2023-11-30T21:21:52ZengMDPI AGBiomolecules2218-273X2022-12-011313810.3390/biom13010038Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse ModelsYu Zhao0Longlong Zhang1Daqi Wang2Bing Chen3Yilai Shu4ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, ChinaInner ear gene therapy using adeno-associated viral vectors (AAVs) in neonatal mice can alleviate hearing loss in mouse models of deafness. However, efficient and safe transgene delivery to the adult mouse cochlea is critical for the effectiveness of AAV-mediated therapy. Here, we examined three gene delivery approaches including posterior semicircular canal (PSCC) canalostomy, round window membrane (RWM) injection, and tubing-RWM+PSCC (t-RP) in adult mice. Transduction rates and survival rates of cochlear hair cells were analyzed, hearing function was recorded, AAV distribution in the sagittal brain sections was evaluated, and cochlear histopathologic images were appraised. We found that an injection volume of 1 μL AAV through the PSCC is safe and highly efficient and does not impair hearing function in adult mice, but local injection allows AAV vectors to spread slightly into the brain. We then tested five AAV serotypes (PHP.eB, IE, Anc80L65, AAV2, and PHP.s) in parallel and observed the most robust eGFP expression in inner hair cells, outer hair cells, and spiral ganglion neurons throughout the cochlea after AAV-Anc80L65 injection. Thus, PSCC-injected Anc80L65 provides a foundation for gene therapy in the adult cochlea and will facilitate the development of inner ear gene therapy.https://www.mdpi.com/2218-273X/13/1/38gene therapyAAVadult mousePSCCRWM |
| spellingShingle | Yu Zhao Longlong Zhang Daqi Wang Bing Chen Yilai Shu Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models Biomolecules gene therapy AAV adult mouse PSCC RWM |
| title | Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models |
| title_full | Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models |
| title_fullStr | Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models |
| title_full_unstemmed | Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models |
| title_short | Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models |
| title_sort | approaches and vectors for efficient cochlear gene transfer in adult mouse models |
| topic | gene therapy AAV adult mouse PSCC RWM |
| url | https://www.mdpi.com/2218-273X/13/1/38 |
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