Altering gene expression using antisense oligonucleotide therapy for hearing loss

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.