Background: Hearing impairment is the most frequent sensory deficit, affecting 466 million people worldwide and has been listed by the World Health Organization (WHO) as one of the priority diseases for research into therapeutic interventions to address public health needs. Inner ear gene therapy is a promising approach to restore sensorineural hearing loss, for which several gene therapy applications have been studied and reported in preclinical animal studies. Objective: To perform a systematic review on preclinical studies reporting cochlear gene therapy, with a specific focus on transduction efficiency. Methods: An initial PubMed search was performed on April 1st 2021 using the PRISMA methodology. Preclinical in vivo studies reporting primary data regarding transduction efficiency of gene therapy targeting the inner ear were included in this report. Results: Thirty-six studies were included in this review. Transduction of various cell types in the inner ear can be achieved, according to the viral vector used. However, there is significant variability in the applied vector delivery systems, including promoter, viral vector titer, etc. Conclusion: Although gene therapy presents a promising approach to treat sensorineural hearing loss in preclinical studies, the heterogeneity of methodologies impedes the identification of the most promising tools for future use in inner ear therapies.

中文翻译：

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用于耳蜗基因治疗的病毒载体的转导效率和免疫原性：临床前动物研究的系统评价。


背景：听力障碍是最常见的感觉缺陷，影响着全球 4.66 亿人，已被世界卫生组织 (WHO) 列为研究治疗干预措施以满足公共卫生需求的优先疾病之一。内耳基因治疗是恢复感音神经性听力损失的一种有前途的方法，在临床前动物研究中已经研究和报告了几种基因治疗应用。目的：对报告耳蜗基因治疗的临床前研究进行系统评价，特别关注转导效率。方法：2021 年 4 月 1 日使用 PRISMA 方法进行了初步 PubMed 检索。本报告中包括报告有关针对内耳的基因治疗转导效率的主要数据的临床前体内研究。结果：本次评价纳入了 36 项研究。根据所使用的病毒载体，可以实现内耳中各种细胞类型的转导。然而，所应用的载体递送系统存在显着差异，包括启动子、病毒载体滴度等。结论：尽管基因治疗在临床前研究中提供了一种治疗感音神经性听力损失的有前途的方法，但方法的异质性阻碍了最重要治疗方法的识别。未来用于内耳治疗的有前途的工具。