Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential

Hearing loss imposes a significant global health burden and often results from genetic factors and various external influences, such as noise exposure and the use of ototoxic drugs. Recent advancements in adeno-associated virus (AAV)-mediated gene therapy offer promising new avenues for the treatment of inner ear diseases. Clinical trials of AAV-mediated gene therapies show impressive preliminary results, although further research is needed to evaluate the safety and long-term effects of these therapies. Preclinical AAV-mediated gene therapy is notable for its high transduction efficiency and safety. In this article, the development of AAV-mediated gene therapies is reviewed for inner ear diseases, categorizing these therapies by their strategies for treating hereditary hearing loss, including gene replacement and cluster regularly interspaced short palindromic repeat-based methods. AAV-mediated hair cell regeneration therapy is also reviewed for acquired hearing loss, as well as methods to prevent acquired hearing loss. In this article, it is hoped to provide a comprehensive overview of recent progress in AAV-mediated gene therapy and its future potential, thereby highlighting the importance of this therapy for researchers and clinicians in the field.