Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss
Abstract Hearing loss is a common disability affecting the world’s population today. While several studies have shown that inner ear gene therapy can be successfully applied to mouse models of hereditary hearing loss to improve hearing, most of these studies rely on inner ear gene delivery in the ne...
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| Format: | Article |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-98412-y |
| _version_ | 1819198457486770176 |
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| author | Jianliang Zhu Jin Woong Choi Yasuko Ishibashi Kevin Isgrig Mhamed Grati Jean Bennett Wade Chien |
| author_facet | Jianliang Zhu Jin Woong Choi Yasuko Ishibashi Kevin Isgrig Mhamed Grati Jean Bennett Wade Chien |
| author_sort | Jianliang Zhu |
| collection | DOAJ |
| description | Abstract Hearing loss is a common disability affecting the world’s population today. While several studies have shown that inner ear gene therapy can be successfully applied to mouse models of hereditary hearing loss to improve hearing, most of these studies rely on inner ear gene delivery in the neonatal age, when mouse inner ear has not fully developed. However, the human inner ear is fully developed at birth. Therefore, in order for inner ear gene therapy to be successfully applied in patients with hearing loss, one must demonstrate that gene delivery can be safely and reliably performed in the mature mammalian inner ear. In this study, we examine the steps involved in posterior semicircular canal gene delivery in the adult mouse inner ear. We find that the duration of perilymphatic leakage and injection rate have a significant effect on the post-surgical hearing outcome. Our results show that although AAV2.7m8 has a lower hair cell transduction rate in adult mice compared to neonatal mice at equivalent viral load, AAV2.7m8 is capable of transducing the adult mouse inner and outer hair cells with high efficiency in a dose-dependent manner. |
| first_indexed | 2024-12-23T03:00:45Z |
| format | Article |
| id | doaj.art-2565d988c0004b17a47e54b96a9b72b4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T03:00:45Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2565d988c0004b17a47e54b96a9b72b42022-12-21T18:02:26ZengNature PortfolioScientific Reports2045-23222021-09-0111111010.1038/s41598-021-98412-yRefining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing lossJianliang Zhu0Jin Woong Choi1Yasuko Ishibashi2Kevin Isgrig3Mhamed Grati4Jean Bennett5Wade Chien6Inner Ear Gene Therapy Program, National Institute On Deafness and Other Communication Disorders (NIDCD), National Institutes of HealthInner Ear Gene Therapy Program, National Institute On Deafness and Other Communication Disorders (NIDCD), National Institutes of HealthInner Ear Gene Therapy Program, National Institute On Deafness and Other Communication Disorders (NIDCD), National Institutes of HealthInner Ear Gene Therapy Program, National Institute On Deafness and Other Communication Disorders (NIDCD), National Institutes of HealthInner Ear Gene Therapy Program, National Institute On Deafness and Other Communication Disorders (NIDCD), National Institutes of HealthCenter for Advanced Retinal and Ocular Therapeutics, University of Pennsylvania Perelman School of MedicineInner Ear Gene Therapy Program, National Institute On Deafness and Other Communication Disorders (NIDCD), National Institutes of HealthAbstract Hearing loss is a common disability affecting the world’s population today. While several studies have shown that inner ear gene therapy can be successfully applied to mouse models of hereditary hearing loss to improve hearing, most of these studies rely on inner ear gene delivery in the neonatal age, when mouse inner ear has not fully developed. However, the human inner ear is fully developed at birth. Therefore, in order for inner ear gene therapy to be successfully applied in patients with hearing loss, one must demonstrate that gene delivery can be safely and reliably performed in the mature mammalian inner ear. In this study, we examine the steps involved in posterior semicircular canal gene delivery in the adult mouse inner ear. We find that the duration of perilymphatic leakage and injection rate have a significant effect on the post-surgical hearing outcome. Our results show that although AAV2.7m8 has a lower hair cell transduction rate in adult mice compared to neonatal mice at equivalent viral load, AAV2.7m8 is capable of transducing the adult mouse inner and outer hair cells with high efficiency in a dose-dependent manner.https://doi.org/10.1038/s41598-021-98412-y |
| spellingShingle | Jianliang Zhu Jin Woong Choi Yasuko Ishibashi Kevin Isgrig Mhamed Grati Jean Bennett Wade Chien Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss Scientific Reports |
| title | Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss |
| title_full | Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss |
| title_fullStr | Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss |
| title_full_unstemmed | Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss |
| title_short | Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss |
| title_sort | refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss |
| url | https://doi.org/10.1038/s41598-021-98412-y |
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