Neuroscience Center of Excellence, LSUHSC, New Orleans, LA, USA.
Department of Otorhinolaryngology, RUMC, Geert Grooteplein 10, Route 855, GA, Nijmegen 6525, the Netherlands; Donders Institute for Brain, Cognition, and Behavior, RUMC, Nijmegen, NL.
Hear Res. 2022 Dec;426:108523. doi: 10.1016/j.heares.2022.108523. Epub 2022 May 16.
Hearing loss affects more than 430 million people, worldwide, and is the third most common chronic physical condition in the United States and Europe (GBD Hearing Loss Collaborators, 2021; NIOSH, 2021; WHO, 2021). The loss of hearing significantly impacts motor and cognitive development, communication, education, employment, and overall quality of life. The inner ear houses the sensory organs for both hearing and balance and provides an accessible target for therapeutic delivery. Antisense oligonucleotides (ASOs) use various mechanisms to manipulate gene expression and can be tailor-made to treat disorders with defined genetic targets. In this review, we discuss the preclinical advancements within the field of the highly promising ASO-based therapies for hereditary hearing loss disorders. Particular focus is on ASO mechanisms of action, preclinical studies on ASO treatments of hearing loss, timing of therapeutic intervention, and delivery routes to the inner ear.
全球有超过 4.3 亿人受到听力损失的影响，在美国和欧洲，听力损失是第三大常见的慢性身体疾病（GBD 听力损失协作组，2021 年；NIOSH，2021 年；世界卫生组织，2021 年）。听力损失会严重影响运动和认知发育、沟通、教育、就业和整体生活质量。内耳是听觉和平衡的感觉器官所在地，为治疗提供了一个可触及的目标。反义寡核苷酸 (ASO) 使用各种机制来操纵基因表达，并且可以针对具有明确遗传靶点的疾病进行定制治疗。在这篇综述中，我们讨论了遗传性听力损失疾病中基于 ASO 的治疗方法的临床前进展。特别关注 ASO 的作用机制、ASO 治疗听力损失的临床前研究、治疗干预的时间以及向内耳输送的途径。
