Genome editing in the treatment of ocular diseases

• Published in: Experimental & molecular medicine 2023-08, Vol.55 (8), p.1678-1690
• Main Authors: Choi, Elliot H., Suh, Susie, Sears, Avery E., Hołubowicz, Rafał, Kedhar, Sanjay R., Browne, Andrew W., Palczewski, Krzysztof
• Format: Article
• Language: English
• Subjects: 631/1647/1511; 631/61/201/2110; 692/700/565/201/2110; Animal models; Biomedical and Life Sciences; Biomedicine; Clinical medicine; Clinical trials; CRISPR; Eye diseases; Gene Editing - methods; Gene therapy; Genetic engineering; Genetic Therapy - methods; Genome editing; Genomes; Glaucoma; Herpes simplex; Humans; Immune privilege; Inflammation; Medical Biochemistry; Molecular Medicine; Review; Review Article; Stem Cells; Therapeutic applications
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-01057-2

Genome-editing technologies have ushered in a new era in gene therapy, providing novel therapeutic strategies for a wide range of diseases, including both genetic and nongenetic ocular diseases. These technologies offer new hope for patients suffering from previously untreatable conditions. The unique anatomical and physiological features of the eye, including its immune-privileged status, size, and compartmentalized structure, provide an optimal environment for the application of these cutting-edge technologies. Moreover, the development of various delivery methods has facilitated the efficient and targeted administration of genome engineering tools designed to correct specific ocular tissues. Additionally, advancements in noninvasive ocular imaging techniques and electroretinography have enabled real-time monitoring of therapeutic efficacy and safety. Herein, we discuss the discovery and development of genome-editing technologies, their application to ocular diseases from the anterior segment to the posterior segment, current limitations encountered in translating these technologies into clinical practice, and ongoing research endeavors aimed at overcoming these challenges. Eye disease: gene editing offers new treatment possibilities Using gene editing tools to correct gene mutations and manipulate specific tissues in the eye could revolutionize treatment for multiple eye diseases. Krzysztof Palczewski and co-workers at the University of California in Irvine, USA, reviewed the current status of gene editing tools such as CRISPR-Cas9 for eye diseases. The eye’s special ‘immune privilege’ status means it can tolerate therapeutic interventions without excessive inflammatory responses. The eye is also easy to image for monitoring. Recent successful trials on mouse models include gene editing treatments for glaucoma and inherited retinal diseases. Initial human trials using CRISPR-Cas9 to treat an eye condition triggered by the herpes simplex virus showed promise. The latest generation of gene editing tools and delivery systems are increasingly precise, limiting unwanted side effects. However, challenges remain in bringing this technology into clinical practice.