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. 2017 Sep;5(3):199-206.
doi: 10.1007/s40135-017-0144-1. Epub 2017 Jun 15.

CRISPR-mediated Ophthalmic Genome Surgery

Galaxy Y Cho  1   2 , Yazeed Abdulla  3 , Jesse D Sengillo  1   4 , Sally Justus  1   5 , Kellie A Schaefer  6 , Alexander G Bassuk  7 , Stephen H Tsang  1   2   5 , Vinit B Mahajan  8   9
Affiliations

CRISPR-mediated Ophthalmic Genome Surgery

Galaxy Y Cho et al. Curr Ophthalmol Rep. 2017 Sep.

Abstract

Purpose of review: Clustered regularly interspaced short palindromic repeats (CRISPR) is a genome engineering system with great potential for clinical applications due to its versatility and programmability. This review highlights the development and use of CRISPR-mediated ophthalmic genome surgery in recent years.

Recent findings: Diverse CRISPR techniques are in development to target a wide array of ophthalmic conditions, including inherited and acquired conditions. Preclinical disease modeling and recent successes in gene editing suggest potential efficacy of CRISPR as a therapeutic for inherited conditions. In particular, the treatment of Leber congenital amaurosis with CRISPR-mediated genome surgery is expected to reach clinical trials in the near future.

Summary: Treatment options for inherited retinal dystrophies are currently limited. CRISPR-mediated genome surgery methods may be able to address this unmet need in the future.

Keywords: CRISPR-Cas; genome surgery; induced pluripotent stem cells; inherited retinal dystrophy.

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Figures

Figure 1
Figure 1
CRISPR therapeutic editing has been customized to serve a diverse array of genome engineering needs. (A) CRISPRn (n = nuclease), or the traditional CRISPR system, uses homologous recombination to restore a mutation to wild type; (B) CRISPRd (d = deletion) uses non-homologous end joining to ablate a mutant allele; and (C) CRISPRi (i = interference) uses an inactive Cas9 to bind but not cleave DNA and prevent transcription mechanisms from producing gene expression.
Figure 2
Figure 2
56-year-old man with a heterozygous mutation in RHO, specifically c.800C>T, p.(Pro267Leu). Digital color fundus photography of the right (A) and left (B) eyes illustrate intraretinal pigment migration, attenuated blood vessels, pale discs, and a bulls-eye atrophy. Short wavelength fundus autofluorescence (SW-FAF) of the right (C) and left (D) eyes reveals extensive RPE atrophy outside of the arterial arcades with an inferior predominance. A bulls-eye atrophy in both eyes is more evident with SW-FAF imaging.
Figure 3
Figure 3
12-year-old boy with a hemizygous mutation in RPGR, specifically c.1307G>A, p.(Gly436Asp) in exon 11. Digital color fundus photography of the right (A) and left (B) eyes shows mottling outside of the macula. SW-FAF reveals a typical hyperautofluorescent ring of RP which corresponds to the boundary of an intact and absent ellipsoid zone (EZ) layer. On SD-OCT (E), peripheral thinning is seen outside of the parafovea with preservation of the EZ-line within the central macula only.
See this image and copyright information in PMC

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