CRISPR-Cas9 and the Future of Ocular Retinal Therapy: A New Era for Ocular Disease

Vollständiger Abstract

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Introduction: Diabetic retinopathy and inherited retinal dystrophies cause significant vision impairment globally and are grouped under ocular retinopathies. While traditional therapies are less effective as they only offer symptomatic relief, they run the risk of the disease progressing even further. The advent of the CRISPR-Cas9 gene editing system has the potential to allow the direct disease modification and correction of the diseased state of the gene. Therefore, a paradigm shift can occur where traditional therapies only offer symptomatic relief and disease modification can be offered instead. The objective of this article is to describe the current state of CRISPR-Cas9 for ocular retinopathies from the perspective of disease modification, and incorporate potential barriers to design a framework to assess the future opportunities and obstacles to the CRISPR-Cas9 gene editing system in the clinic. Methods: CRISPR 'Cas9', retinal 'gene editing', 'inherited retinal diseases', 'delivery systems', and a combination of these terms were employed when searching published literature. Studies were published in English, were original research, reviews, or clinical trials, and were peer-reviewed. Studies were excluded if they were not related to the ocular applications of CRISPR. Results: Results from pre-clinical studies or early-stage trials indicate that CRISPR-Cas9 may be used to restore the function of diseased retina and stabilize the further progression of the disease. Delivery systems are becoming more efficient and less likely to elicit immune responses. The expected therapeutic result is higher when all these systems are combined. Next-generation CRISPR editors, together with AI-based RNA design and delivery systems, are expected to improve the editing of the 'epigenome'. Discussion: The combination of CRISPR-Cas9 with cell-based therapies and personalized medicine approaches will continue to improve the precision and effectiveness of a given treatment. Advanced technologies in the field of gene modification and editing, AI-guided RNA therapies, and epigenome editing continue to remove obstacles related to specificity and expand the treatable areas in medicine. Conclusions: The potential of CRISPR-Cas9 in the treatment of Ocular Retinopathies is high given its ability to treat diseases by repairing their genetic causes. Continued off-target and delivery challenges and the slow pace of regulations will hinder the privileged work of multidisciplinary teams that are focused on the potential of CRISPR technologies. The long-term restoration of vision to patients who suffer from Retinal Diseases and improving their vision is not only the goal, but one of the more certain outcomes of this work.