https://scholars.lib.ntu.edu.tw/handle/123456789/637080
標題: | Gene therapy with a synthetic adeno-associated viral vector improves audiovestibular phenotypes in Pjvk-mutant mice | 作者: | Lu, Ying-Chang Tsai, Yi-Hsiu Chan, Yen-Huei Hu, Chin-Ju Huang, Chun-Ying Xiao, Ru Hsu, Chuan-Jen Vandenberghe, Luk H CHEN-CHI WU Cheng, Yen-Fu |
關鍵字: | Gene therapy; Genetic diseases; Neurodegeneration; Neuroscience; Therapeutics | 公開日期: | 24-十月-2022 | 卷: | 7 | 期: | 20 | 來源出版物: | JCI insight | 摘要: | Recessive PJVK mutations that cause a deficiency of pejvakin, a protein expressed in both sensory hair cells and first-order neurons of the inner ear, are an important cause of hereditary hearing impairment. Patients with PJVK mutations garner limited benefits from cochlear implantation; thus, alternative biological therapies may be required to address this clinical difficulty. The synthetic adeno-associated viral vector Anc80L65, with its wide tropism and high transduction efficiency in various inner ear cells, may provide a solution. We delivered the PJVK transgene to the inner ear of Pjvk mutant mice using the synthetic Anc80L65 vector. We observed robust exogenous pejvakin expression in the hair cells and neurons of the cochlea and vestibular organs. Subsequent morphologic and audiologic studies demonstrated significant restoration of spiral ganglion neuron density and hair cells in the cochlea, along with partial recovery of sensorineural hearing impairment. In addition, we observed a recovery of vestibular ganglion neurons and balance function to WT levels. Our study demonstrates the utility of Anc80L65-mediated gene delivery in Pjvk mutant mice and provides insights into the potential of gene therapy for PJVK-related inner ear deficits. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637080 | ISSN: | 2379-3708 | DOI: | 10.1172/jci.insight.152941 |
顯示於: | 醫學系 |
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