Deafness: from genetic architecture to gene therapy

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• Human genetic studies and mouse models have elucidated the molecular basis of the auditory system.
• The cochlea, the organ of hearing, is central to understanding auditory function and dysfunction.

Purpose of the Study:

• To review progress in understanding the genetic architecture of sensorineural hearing impairment (SNHI).
• To discuss the potential of gene therapy for treating SNHI and associated balance disorders.

Main Methods:

• Deciphering genetic architecture of SNHI.
• Multidisciplinary studies of mouse models.
• Elucidation of molecular mechanisms in the cochlea.

Main Results:

• Unparalleled insights into pathophysiological processes of SNHI.
• Identification of molecular mechanisms underlying auditory system function.

Conclusions:

• Preclinical gene therapy studies highlight translational opportunities and challenges.
• Gene replacement, augmentation, and editing offer potential for treating monogenic SNHI and balance disorders.