Clustered Regularly Interspaced Short Palindromic Repeats: Challenges in Treating Retinal Disease

• Type of Material: Article
• Authors: Micah A. Chrenek, Emory University; John Nickerson, Emory University; Jeffrey Boatright, Emory University
• Language: English
• Date: 2016-07-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2006 Lippincott Williams & Wilkins.
• Final Published Version (URL): http://dx.doi.org/10.1097/APO.0000000000000225
• Title of Journal or Parent Work: Asia-Pacific Journal of Ophthalmology
• ISSN: 2162-0989
• Volume: 5
• Issue: 4
• Start Page: 304
• End Page: 308
• Grant/Funding Information: We are grateful for support provided by the Abraham J. & Phyllis Katz Foundation (J.H.B.), NIH R01EY014026 (J.H.B.), R01EY021592 (J.M.N.), R01EY016470 (J.M.N.), VA RR&D C1924P I21RX001924 (J.H.B.), VA RR&D C9246C (Atlanta VA Center of Excellence in Vision and Neurocognitive Rehabilitation), P30EY006360, and an unrestricted grant to the Department of Ophthalmology at Emory University from Research to Prevent Blindness, Inc.
• Keywords: Genetic Therapy; Genomics; Clustered Regularly Interspaced Short Palindromic Repeats; Retinal Diseases; Gene Transfer Techniques; RNA Editing; Humans
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

Ophthalmic researchers and clinicians arguably have led the way for safe, effective gene therapy, most notably with adeno-associated viral gene supplementation in the treatment for patients with Leber congenital amaurosis type 2 with mutations in the RPE65 gene. These successes notwithstanding, most other genetic retinal disease will be refractory to supplementation. The ideal gene therapy approach would correct gene mutations to restore normal function in the affected cells. Gene editing in which a mutant allele is inactivated or converted to sequence that restores normal function is hypothetically one such approach. Such editing involves site-specific digestion of mutant genomic DNA followed by repair. Previous experimental approaches were hampered by inaccurate and high rates of off-site lesioning and by overall low digestion rates. A new tool, clustered regularly interspaced short palindromic repeats coupled with the nuclease Cas9, may address both shortcomings. Some of the many challenges that must be addressed in moving clustered regularly interspaced short palindromic repeats coupled with the nuclease Cas9 therapies to the ophthalmic clinic are discussed here.