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Review
. 2021 Mar 17:15:652215.
doi: 10.3389/fnins.2021.652215. eCollection 2021.

Gene Therapy to the Retina and the Cochlea

Ryan Crane  1 , Shannon M Conley  2   3 , Muayyad R Al-Ubaidi  1   4   5 , Muna I Naash  1   4   5
Affiliations
Review

Gene Therapy to the Retina and the Cochlea

Ryan Crane et al. Front Neurosci. .

Abstract

Vision and hearing disorders comprise the most common sensory disorders found in people. Many forms of vision and hearing loss are inherited and current treatments only provide patients with temporary or partial relief. As a result, developing genetic therapies for any of the several hundred known causative genes underlying inherited retinal and cochlear disorders has been of great interest. Recent exciting advances in gene therapy have shown promise for the clinical treatment of inherited retinal diseases, and while clinical gene therapies for cochlear disease are not yet available, research in the last several years has resulted in significant advancement in preclinical development for gene delivery to the cochlea. Furthermore, the development of somatic targeted genome editing using CRISPR/Cas9 has brought new possibilities for the treatment of dominant or gain-of-function disease. Here we discuss the current state of gene therapy for inherited diseases of the retina and cochlea with an eye toward areas that still need additional development.

Keywords: animal models; cochlea; gene therapy; nanoparticles; retina.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic Illustrations of the Cochlea and Retina. (A) The structure of the eye, (B) layers of the retina (Sc, sclera; CBV, choroidal blood vessel; BM, Bruch’s membrane; RPE, retinal pigment epithelium; PR, photoreceptors; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer) and (C) The structure of the inner ear, (D) cross-section of the cochlea and a close-up of the Organ of Corti. Shown are selected genes which are associated with disease in humans. Genes marked in red represent a selection of those that have been evaluated successfully in animal models while those in blue have been evaluated in human clinical trials. Images were created with BioRender.com.
FIGURE 2
FIGURE 2
Site of Usher proteins in the retina and the cochlea. Shown are illustrations of the photoreceptor and hair cell highlighting the regions affected by different Usher syndrome genes. Ush1 genes/locations are shown in cyan, Ush2 genes/locations in purple, and Ush 3 genes in lime green. Hair cell legend structures: ankle links (purple), lateral links (green), contact region (gold), tip link (red), kinocilium links (blue), kinocilium (K). Images were created with BioRender.com.
FIGURE 3
FIGURE 3
Injection sites into the retina and the cochlea. Shown are (A) the three major injection sites for delivery to the retina and (B) the three main injection locations for the cochlea. Images were created with BioRender.com.
See this image and copyright information in PMC

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