CRISPR-Cas Genome Surgery in Ophthalmology

Abstract

Genetic disease affecting vision can significantly impact patient quality of life. Gene therapy seeks to slow the progression of these diseases by treating the underlying etiology at the level of the genome. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated systems (Cas) represent powerful tools for studying diseases through the creation of model organisms generated by targeted modification and by the correction of disease mutations for therapeutic purposes. CRISPR-Cas systems have been applied successfully to the visual sciences and study of ophthalmic disease – from the modification of zebrafish and mammalian models of eye development and disease, to the correction of pathogenic mutations in patient-derived stem cells. Recent advances in CRISPR-Cas delivery and optimization boast improved functionality that continues to enhance genome-engineering applications in the eye. This review provides a synopsis of the recent implementations of CRISPR-Cas tools in the field of ophthalmology.

Recent developments in regenerative ophthalmology

“…This system consists of Cas9 nuclease and sgRNA. Under the guidance of sgRNA, the specific splicing by Cas9 nuclease of target DNA is primarily performed via identification of the conserved protospacer adjacent motif (DiCarlo et al, 2017). Following breakage, the target DNA can be repaired via two mechanisms.…”

Gene therapy and genome surgery in the retina

“…Moreover, Allergan is sponsoring a phase I/ II trial of an intravitreally delivered channelrhodospin-2-based optogenetic therapy, RST-100, in patients with advanced RP (174). Further developments in clinical application for other causative mutation retinal dystrophies are highly anticipated, as patients suffering from blinding inherited eye disease may gain options for previously untreatable conditions (175)(176)(177)(178)(179).…”

Attenuation of Inherited and Acquired Retinal Degeneration Progression with Gene-based Techniques

“…The term genome surgery relates to CRISPR gene editing which has the ability to edit, delete, and epigenetically modify DNA in vivo [5,23,25]. Although both traditional gene therapy and genome "surgery" require intraoperative sub-retinal delivery, the term "genome surgery" was coined as a depiction of the molecular process taking place.…”

“…Still, it should be noted that care must be taken when utilizing viral vectors [21] as the blood-retinal barrier may be compromised in retinal disease [22] potentially leading to inflammation or other host immune response. Still, the eye proves further to be an ideal subject of study as clinicians can non-invasively monitor the eye for treatment response and signs of adverse reactions to such novel treatments [1,[23][24][25].…”