Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transl Med. Apr 12, 2016; 5(1): 1-13
Published online Apr 12, 2016. doi: 10.5528/wjtm.v5.i1.1
Gene editing for corneal disease management
Sudhanshu P Raikwar, Apoorva S Raikwar, Shyam S Chaurasia, Rajiv R Mohan
Sudhanshu P Raikwar, Shyam S Chaurasia, Rajiv R Mohan, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, United States
Sudhanshu P Raikwar, Rajiv R Mohan, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO 65201, United States
Apoorva S Raikwar, Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
Rajiv R Mohan, Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO 65212, United States
Rajiv R Mohan, Ophthalmology and Molecular Medicine, One-health One-Medicine Ophthalmology and Vision Research, University of Missouri, Columbia, MO 65211, United States
Author contributions: Raikwar SP made substantial contributions in study design, literature, review, drafting the article and making critical revisions; Raikwar AS made graphic design; Chaurasia SS made critical reading; Mohan RR made substantial contributions in conception, study design, critical reading, graphic design, final approval, and submission of manuscript.
Supported by Veteran Health Affairs Merit grant, No. 1I01BX000357-05 (to Mohan RR); National Eye Institute, NIH grant, R01EY017294 (to Mohan RR); and the Ruth M. Kraeuchi Missouri Endowment of Ophthalmology (to Mohan RR).
Conflict-of-interest statement: There is no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Rajiv R Mohan, PhD, FARVO, Professor, Ophthalmology and Molecular Medicine, One-health One-Medicine Ophthalmology and Vision Research, University of Missouri, 1600 E. Rollins Road, Columbia, MO 65211, United States. mohanr@health.missouri.edu
Telephone: +1-573-8841449 Fax: +1-573-8844100
Received: September 29, 2015
Peer-review started: October 2, 2015
First decision: November 10, 2015
Revised: November 21, 2015
Accepted: March 7, 2016
Article in press: March 9, 2016
Published online: April 12, 2016
Processing time: 69 Days and 0.3 Hours
Abstract

Gene editing has recently emerged as a promising technology to engineer genetic modifications precisely in the genome to achieve long-term relief from corneal disorders. Recent advances in the molecular biology leading to the development of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR-associated systems, zinc finger nucleases and transcription activator like effector nucleases have ushered in a new era for high throughput in vitro and in vivo genome engineering. Genome editing can be successfully used to decipher complex molecular mechanisms underlying disease pathophysiology, develop innovative next generation gene therapy, stem cell-based regenerative therapy, and personalized medicine for corneal and other ocular diseases. In this review we describe latest developments in the field of genome editing, current challenges, and future prospects for the development of personalized gene-based medicine for corneal diseases. The gene editing approach is expected to revolutionize current diagnostic and treatment practices for curing blindness.

Keywords: Adeno-associated virus; Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9; Cornea; Clustered Regularly Interspaced Short Palindromic Repeat; Double strand breaks; Gene editing; sgRNA; Gene targeting; Homology directed repair; Homologous recombination; Indels; Lentiviral vector; Protospacer-adjacent motif; Transcription activator like effector nucleases; Zinc finger nucleases

Core tip: Gene editing technology including Clustered Regularly Interspaced Short Palindromic Repeats/Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9, zinc finger nucleases, or transcription activator like effector nucleases has great potential for generating in vitro and in vivo models of corneal diseases including keratoconus and Fuchs’ endothelial corneal dystrophy. Furthermore, gene editing is a powerful tool for studying molecular mechanisms mediating corneal development, pathogenesis and developing next generation innovative gene therapies including the patient-specific personalized medicine for curing corneal diseases. This review discusses current status and latest developments in the field of gene editing. Gene editing based molecular therapy has the potential to revolutionize current practices in ophthalmology clinic for curing corneal blindness.