Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model
Abstract GJB2 encodes connexin 26 (Cx26), the most commonly mutated gene causing hereditary non‐syndromic hearing loss. Cx26 is mainly expressed in supporting cells (SCs) and fibrocytes in the mammalian cochlea. Gene therapy is currently considered the most promising strategy for eradicating genetic...
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406510 |
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| author | Xiaohui Wang Li Zhang Sen Chen Le Xie Yue Qiu Chenyang Kong Ge Yin Weijia Kong Yu Sun |
| author_facet | Xiaohui Wang Li Zhang Sen Chen Le Xie Yue Qiu Chenyang Kong Ge Yin Weijia Kong Yu Sun |
| author_sort | Xiaohui Wang |
| collection | DOAJ |
| description | Abstract GJB2 encodes connexin 26 (Cx26), the most commonly mutated gene causing hereditary non‐syndromic hearing loss. Cx26 is mainly expressed in supporting cells (SCs) and fibrocytes in the mammalian cochlea. Gene therapy is currently considered the most promising strategy for eradicating genetic diseases. However, there have been no significant effects of gene therapy for GJB2 gene mutation‐associated deafness because deficiency of Cx26 leads to expanded sensory epithelial damage. In this study, the AAV2.7m8 serotype combined with the gfaABC1D promoter targeted infection of SCs is identified. It is found that Gjb2 gene replacement therapy in wild‐type mice results in sensory hair cells (HCs) deficits, excessive inflammatory responses, and hearing loss. This may be one of the key factors contributing to the hardship of GJB2 gene replacement therapy. Dexamethasone (DEX) shows promising results in inhibiting macrophage recruitment, with a protective effect against HC damage. Further, the combination of AAV2.7m8‐Gjb2 with DEX shows a synergistic effect and enhances the gene therapy effect in a conditional Cx26 null mice model. These results indicate that the combination of gene therapy and medication will provide a new strategy for the treatment of hereditary deafness associated with GJB2 defects. |
| format | Article |
| id | doaj-art-d5d91afde76f4607bd40cd0a5859ac3f |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d5d91afde76f4607bd40cd0a5859ac3f2025-08-20T02:57:53ZengWileyAdvanced Science2198-38442025-08-011229n/an/a10.1002/advs.202406510Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice ModelXiaohui Wang0Li Zhang1Sen Chen2Le Xie3Yue Qiu4Chenyang Kong5Ge Yin6Weijia Kong7Yu Sun8Department of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaAbstract GJB2 encodes connexin 26 (Cx26), the most commonly mutated gene causing hereditary non‐syndromic hearing loss. Cx26 is mainly expressed in supporting cells (SCs) and fibrocytes in the mammalian cochlea. Gene therapy is currently considered the most promising strategy for eradicating genetic diseases. However, there have been no significant effects of gene therapy for GJB2 gene mutation‐associated deafness because deficiency of Cx26 leads to expanded sensory epithelial damage. In this study, the AAV2.7m8 serotype combined with the gfaABC1D promoter targeted infection of SCs is identified. It is found that Gjb2 gene replacement therapy in wild‐type mice results in sensory hair cells (HCs) deficits, excessive inflammatory responses, and hearing loss. This may be one of the key factors contributing to the hardship of GJB2 gene replacement therapy. Dexamethasone (DEX) shows promising results in inhibiting macrophage recruitment, with a protective effect against HC damage. Further, the combination of AAV2.7m8‐Gjb2 with DEX shows a synergistic effect and enhances the gene therapy effect in a conditional Cx26 null mice model. These results indicate that the combination of gene therapy and medication will provide a new strategy for the treatment of hereditary deafness associated with GJB2 defects.https://doi.org/10.1002/advs.202406510AAV2.7m8dexamethasonegene therapyGJB2hearing loss |
| spellingShingle | Xiaohui Wang Li Zhang Sen Chen Le Xie Yue Qiu Chenyang Kong Ge Yin Weijia Kong Yu Sun Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model Advanced Science AAV2.7m8 dexamethasone gene therapy GJB2 hearing loss |
| title | Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model |
| title_full | Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model |
| title_fullStr | Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model |
| title_full_unstemmed | Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model |
| title_short | Viral‐Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model |
| title_sort | viral mediated connexin 26 expression combined with dexamethasone rescues hearing in a conditional gjb2 null mice model |
| topic | AAV2.7m8 dexamethasone gene therapy GJB2 hearing loss |
| url | https://doi.org/10.1002/advs.202406510 |
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