Gene Therapy for Inherited Hearing Loss: Updates and Remaining Challenges

Abstract

Hearing loss stands as the most prevalent sensory deficit among humans, posing a significant global health challenge. Projections indicate that by 2050, approximately 10% of the world's population will grapple with disabling hearing impairment. While approximately half of congenital hearing loss cases have a genetic etiology, traditional interventions such as hearing aids and cochlear implants do not completely restore normal hearing. The absence of biological treatment has prompted significant efforts in recent years, with a strong focus on gene therapy to address hereditary hearing loss. Although several studies have exhibited promising recovery from common forms of genetic deafness in mouse models, existing challenges must be overcome to make gene therapy applicable in the near future. Herein, we summarize the primary gene therapy strategies employed over past years, provide an overview of the recent achievements in preclinical studies for genetic hearing loss, and outline the current key obstacles to cochlear gene therapy.

Keywords: cochlea; deafness; delivery; editing; genetics; genomics; inner ear.

Figure 1

Schematic illustration of the organ of Corti, including the expression sites of causal genes of hearing loss. All genes are part of proof-of-concept studies for inner ear gene therapy.

Figure 2

Schematic illustration of inner-ear gene therapy routes.