Genome editing: the breakthrough technology for inherited retinal disease?

ABSTRACT

Introduction: Genetic alterations resulting in a dysfunctional retinal pigment epithelium and/or degenerating photoreceptors cause impaired vision. These juxtaposed cells in the retina of the posterior eye are crucial for the visual cycle or phototransduction. Deficits in these biochemical processes perturb neural processing of images capturing the external environment. Notably, there is a distinct lack of clinically approved pharmacological, cell- or gene-based therapies for inherited retinal disease. Gene editing technologies are rapidly advancing as a realistic therapeutic option.

Areas covered: Recent discovery of endonuclease-mediated gene editing technologies has culminated in a surge of investigations into their therapeutic potential. In this review, the authors discuss gene editing technologies and their applicability in treating inherited retinal diseases, the limitations of the technology and the research obstacles to overcome before editing a patient’s genome becomes a viable treatment option.

Expert opinion: The ability to strategically edit a patient’s genome constitutes a treatment revolution. However, concerns remain over the safety and efficacy of either transplanting iPSC-derived retinal cells following ex vivo gene editing, or with direct gene editing in vivo. Ultimately, further refinements to improve efficacy and safety profiles are paramount for gene editing to emerge as a widely available treatment option.

KEYWORDS:

• Retina
• photoreceptor
• retinal pigment epithelium
• inherited retinal disease
• gene editing
• CRISPR

Article Highlights

• Gene editing is emerging as an attractive novel treatment strategy for inherited retinal disease.

• Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology is currently the leading gene editing technology positioned for therapeutic intervention.

• In vitro, gene editing can correct mutations in patient derived induced pluripotent stem cells (iPSCs). However concerns remain over integration of transplanted retinal cells.

• In vivo, CRISPR-Cas9, guide RNAs and repair templates to correct specific mutations can be delivered directly into the eye.

• Proof of concept studies show safety and efficacy in rodent models and a clinical trial is planned for 2017.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript is funded by a grant from the Wellcome Trust (WT106820MA), The Irish Research Council [GOIPG/2014/683] and the Fighting Blindness and the Health Research Board in Ireland under Grant No: MRCG/2014/3.