Ocular delivery of CRISPR/Cas genome editing components for treatment of eye diseases

• Published in: Advanced drug delivery reviews Vol. 168; pp. 181 - 195
• Main Authors: Yu, Wenhan, Wu, Zhijian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2021
• Subjects: AAV vector; CRISPR/Cas; Gene delivery; Gene therapy; Genome editing; Retinal degeneration; Retinal degeneration; Gene delivery; AAV vector; Genome editing; Gene therapy; CRISPR/Cas
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/j.addr.2020.06.011

A variety of inherited or multifactorial ocular diseases call for novel treatment paradigms. The newly developed genome editing technology, CRISPR, has shown great promise in treating these diseases, but delivery of the CRISPR/Cas components to target ocular tissues and cells requires appropriate use of vectors and routes of administration to ensure safety, efficacy and specificity. Although adeno-associated viral (AAV) vectors are thus far the most commonly used tool for ocular gene delivery, sustained expression of CRISPR/Cas components may cause immune reactions and an increased risk of off-target editing. In this review, we summarize the ocular administration routes and discuss the advantages and disadvantages of viral and non-viral vectors for delivery of CRISPR/Cas components to the eye. We review the existing studies of CRISPR/Cas genome editing for ocular diseases and discuss the major challenges of the technology in ocular applications. We also discuss the most recently developed CRISPR tools such as base editing and prime editing which may be used for future ocular applications. [Display omitted]