| 项目编号 | PRJCA049089 | ||||||||||||||||
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| 项目标题 | CRISPR-free RNA Base Editing Mediated PTC-readthrough Restores Hearing in Mice with Otof Nonsense Mutation | ||||||||||||||||
| 涉及领域 | Medical | ||||||||||||||||
| 数据类型 |
Epigenomics
Transcriptome or Gene expression |
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| 物种名称 | Mus musculus | ||||||||||||||||
| 描述信息 | The gene therapy achieved by AAV-mediated otoferlin overexpression is the most successful congenital deaf therapeutic strategy. However, achieving its physiological and endogenous patterns of expression remains challenging. Here, we generated the homologous mutation Otof c.1315C>T (p.R439*), equivalent to OTOF c.1273C>T (p.R425*) found in humans with profound deafness, to create a nonsense mutation-induced deaf mouse model. We then delivered the 'RESTART v3' system, which is a CRISPR-free RNA base editor for nonsense mutation suppression, into the cochlea of the mice. We achieved physiological otoferlin expression; the edited premature termination codon was reverse-mutated to the original amino acid. We observed significant hearing restoration and enhancement of the behavioral auditory startle reflex. Thus, our study presents a successful RNA editing strategy to significantly restore hereditary deafness in mice carrying the specific Otof nonsense mutation, which holds great promise for future clinical translation. | ||||||||||||||||
| 样品范围 | Multispecies | ||||||||||||||||
| 发布日期 | 2025-10-29 | ||||||||||||||||
| 出版信息 |
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| 项目资金来源 |
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| 提交者 | Wenqing Liu (liuwq21@stu.pku.edu.cn) | ||||||||||||||||
| 提交单位 | Peking University | ||||||||||||||||
| 提交日期 | 2025-10-23 |
| 资源名称 | 描述 |
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| BioSample (20) show | - |