Emerging Gene Therapies for Genetic Hearing Loss

Abstract

Gene therapy, or the treatment of human disease using genetic material, for inner ear dysfunction is coming of age. Recent progress in developing gene therapy treatments for genetic hearing loss has demonstrated tantalizing proof-of-principle in animal models. While successful translation of this progress into treatments for humans awaits, there is growing interest from patients, scientists, clinicians, and industry. Nonetheless, it is clear that a number of hurdles remain, and expectations for total restoration of auditory function should remain tempered until these challenges have been overcome. Here, we review progress, prospects, and challenges for gene therapy in the inner ear. We focus on technical aspects, including routes of gene delivery to the inner ear, choice of vectors, promoters, inner ear targets, therapeutic strategies, preliminary success stories, and points to consider for translating of these successes to the clinic.

Keywords: cochlea; gene therapy; genetic deafness; hair cell; inner ear; spiral ganglion neuron; vestibular; viral vectors.

Fig. 1

Schematic diagram illustrating several routes of delivery for injecting gene therapy vectors into the inner ear. Fluorescent images showing expression of green fluorescent protein were selected from the literature to illustrate use of several AAV vector serotypes and delivery routes from the top right, moving clockwise, they are as follows: cochleostomy, exo-AAV-GFP (György et al. 2017); cochleostomy, AAV8-GFP (Kilpatrick et al., 2011); round window membrane, AAV2-GFP (Akil et al. 2015); posterior semicircular canal, Anc80-GFP (Suzuki et al. 2017). Each fluorescence image is oriented with a single row of inner hair cells at the bottom and three rows of outer hair cells at the top.