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CRISPR GENOME SURGERY IN THE RETINA IN LIGHT OF OFF-TARGETING

Cho, Galaxy Y., MS*,†,‡; Schaefer, Kellie A., BS§; Bassuk, Alexander G., MD, PhD; Tsang, Stephen H., MD, PhD*,†,‡,**; Mahajan, Vinit B., MD, PhD§,††

doi: 10.1097/IAE.0000000000002197
Review

Purpose: Recent concerns regarding the clinical utilization of clustered regularly interspaced short palindromic repeats (CRISPR) involve uncertainties about the potential detrimental effects that many arise due to unintended genetic changes, as in off-target mutagenesis, during CRISPR genome surgery. This review gives an overview of off-targeting detection methods and CRISPR's place in the clinical setting, specifically in the field of ophthalmology.

Results: As CRISPR utilization in the laboratory setting has increased, knowledge regarding CRISPR mechanisms including its off-target effects has also increased. Although a perfect method for achieving 100% specificity is yet to be determined, the past few years have seen many developments in off-targeting detection and in increasing efficacy of CRISPR tools.

Conclusion: The CRISPR system has high potential to be an invaluable therapeutic tool as it has the ability to modify and repair pathogenic retinal lesions. Although it is not yet a perfect system, with further efforts to improve its specificity and efficacy along with careful screening of off-target mutations, CRISPR-mediated genome surgery potential can become maximized and applied to patients.

This review gives an overview of off-targeting detection methods and place of clustered regularly interspaced short palindromic repeats in the clinical setting, specifically in the field of ophthalmology.

*Institute of Human Nutrition, Columbia Stem Cell Initiative, College of Physicians and Surgeons, Columbia University, New York, New York;

Jonas Children's Vision Care, Bernard and Shirlee Brown Glaucoma Laboratory, New York, New York;

Department of Ophthalmology, Columbia University, New York, New York;

§Department of Ophthalmology, Omics Lab, Byers Eye Institute, Stanford University, Palo Alto, California;

Department of Pediatrics, University of Iowa, Iowa City, Iowa;

**Department of Cell Biology and Pathology, Columbia University, New York, New York; and

††Palo Alto Veterans Administration, Palo Alto, California.

Reprint requests: Vinit B. Mahajan, MD, PhD, Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94304; e-mail: vinit.mahajan@stanford.com

V. B. Mahajan and A. G. Bassuk are supported by NIH grants (R01EY026682, R01EY024665, R01EY025225, R01EY024698, and R21AG050437), and Research to Prevent Blindness (RPB), New York, NY. The Barbara & Donald Jonas Laboratory of Regenerative Medicine and Bernard & Shirlee Brown Glaucoma Laboratory are supported by the National Institute of Health (5P30EY019007, R01EY018213, R01EY024698, and R21AG050437), National Cancer Institute Core (5P30CA013696), the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA. S. H. Tsang is a member of the RD-CURE Consortium and is supported by the Tistou and Charlotte Kerstan Foundation, the Schneeweiss Stem Cell Fund, New York State (C029572), the Foundation Fighting Blindness New York Regional Research Center Grant (C-NY05–0705–0312), the Joel Hoffman Fund, the Professor Gertrude Rothschild Stem Cell Foundation, and the Gebroe Family Foundation.

None of the authors has any conflicting interests to disclose.

G. Y. Cho performed the literature searches and composed the manuscript. K. A. Schaefer assisted in the manuscript composition. V. B. Mahajan, A. G. Bassuk, and S. H. Tsang oversaw all aspects of the manuscript preparation and hold final responsibility for contained information.

© 2018 by Ophthalmic Communications Society, Inc.