Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing Loss
This study aimed to investigate the transduction efficiency of triple adeno-associated virus (AAV) vectors in the cochleae of adult mice, focusing on large-gene-associated hearing loss (HL). Additionally, we sought to evaluate the feasibility of cochlear gene therapy in a mouse model of human <i&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/12/590 |
| _version_ | 1797381581183123456 |
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| author | Hidekane Yoshimura Shu Yokota Yutaka Takumi |
| author_facet | Hidekane Yoshimura Shu Yokota Yutaka Takumi |
| author_sort | Hidekane Yoshimura |
| collection | DOAJ |
| description | This study aimed to investigate the transduction efficiency of triple adeno-associated virus (AAV) vectors in the cochleae of adult mice, focusing on large-gene-associated hearing loss (HL). Additionally, we sought to evaluate the feasibility of cochlear gene therapy in a mouse model of human <i>CDH23</i>-mediated HL using the triple AAV approach. To create a reporter protein, we fused EGFP to mCherry, which was then divided into three parts, each packaged in a separate AAV2/2 vector. Four weeks after co-injecting the triple AAV vectors into 4–5-week-old mice, we assessed transduction efficiency. We found that up to 5.9% of inner hair cells were positive for both EGFP and mCherry. Subsequently, we developed triple <i>Cdh23</i> AAV vectors for therapeutic purposes. After administering these vectors to 4- to 5-week-old C57/BL6 mice, we conducted auditory tests and immunohistochemistry studies over a period of 60 weeks. Co-injecting triple <i>Cdh23</i>-AAVs did not alter auditory function or lead to hair cell degeneration. In conclusion, this study confirms the feasibility of the triple-AAV approach for cochlear gene delivery. While this strategy did not produce any treatment effects, our findings suggest that large deafness genes could be potential future targets for cochlear gene therapy. |
| first_indexed | 2024-03-08T20:53:28Z |
| format | Article |
| id | doaj.art-29cf7c29268d475ab23ea5801e185d32 |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-08T20:53:28Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-29cf7c29268d475ab23ea5801e185d322023-12-22T14:00:36ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-11-0145129413942110.3390/cimb45120590Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing LossHidekane Yoshimura0Shu Yokota1Yutaka Takumi2Department of Otorhinolaryngology—Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, JapanDepartment of Otorhinolaryngology—Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, JapanDepartment of Otorhinolaryngology—Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, JapanThis study aimed to investigate the transduction efficiency of triple adeno-associated virus (AAV) vectors in the cochleae of adult mice, focusing on large-gene-associated hearing loss (HL). Additionally, we sought to evaluate the feasibility of cochlear gene therapy in a mouse model of human <i>CDH23</i>-mediated HL using the triple AAV approach. To create a reporter protein, we fused EGFP to mCherry, which was then divided into three parts, each packaged in a separate AAV2/2 vector. Four weeks after co-injecting the triple AAV vectors into 4–5-week-old mice, we assessed transduction efficiency. We found that up to 5.9% of inner hair cells were positive for both EGFP and mCherry. Subsequently, we developed triple <i>Cdh23</i> AAV vectors for therapeutic purposes. After administering these vectors to 4- to 5-week-old C57/BL6 mice, we conducted auditory tests and immunohistochemistry studies over a period of 60 weeks. Co-injecting triple <i>Cdh23</i>-AAVs did not alter auditory function or lead to hair cell degeneration. In conclusion, this study confirms the feasibility of the triple-AAV approach for cochlear gene delivery. While this strategy did not produce any treatment effects, our findings suggest that large deafness genes could be potential future targets for cochlear gene therapy.https://www.mdpi.com/1467-3045/45/12/590gene therapygenetic hearing lossadeno-associated virusprogressive hearing loss |
| spellingShingle | Hidekane Yoshimura Shu Yokota Yutaka Takumi Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing Loss Current Issues in Molecular Biology gene therapy genetic hearing loss adeno-associated virus progressive hearing loss |
| title | Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing Loss |
| title_full | Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing Loss |
| title_fullStr | Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing Loss |
| title_full_unstemmed | Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing Loss |
| title_short | Treatment following Triple-AAV Delivery in Mature Murine Model of Human <i>CDH23</i>-Associated Hearing Loss |
| title_sort | treatment following triple aav delivery in mature murine model of human i cdh23 i associated hearing loss |
| topic | gene therapy genetic hearing loss adeno-associated virus progressive hearing loss |
| url | https://www.mdpi.com/1467-3045/45/12/590 |
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