Recent evidence provides strong support for the safe and effective use of gene therapy in humans with hearing loss. By means of a single local injection of a set of adeno-associated virus (AAV) vectors, hearing was partially restored in several children with neurosensory nonsyndromic autosomal recessive deafness 9 (DFNB9), harboring variants in the OTOF gene. Current research focuses on refining endoscopic and transmastoid injection procedures to reduce risks of side effects, as emerging evidence suggests bidirectional fluid exchanges between the ear and the brain. Moreover, gene editing approaches and novel AAV capsids are successfully tested in animal models and will likely lead to enhanced targeting of the cochlea. Here, we cover the recent advances in cochlear gene therapy, provide an overview of the translational potential of these new approaches for existing and future clinical trials, and highlight the translational implications that remain to be determined for their application in humans.

中文翻译：

---

耳蜗基因疗法的兴起


最近的证据为基因疗法在听力损失患者中的安全有效使用提供了有力支持。通过单次局部注射一组腺相关病毒 （AAV） 载体，几例携带 OTOF 基因变异的神经感觉非综合征性常染色体隐性遗传性耳聋 9 （DFNB9） 患儿的听力部分恢复。目前的研究重点是改进内窥镜和经乳突注射程序以降低副作用的风险，因为新出现的证据表明耳朵和大脑之间存在双向液体交换。此外，基因编辑方法和新型 AAV 衣壳已在动物模型中成功测试，并可能导致耳蜗靶向性增强。在这里，我们介绍了人工耳蜗基因治疗的最新进展，概述了这些新方法在现有和未来临床试验中的转化潜力，并强调了它们在人类中的应用仍有待确定的转化意义。