Columbia University Medical Center

CRISPR Used to Repair Blindness-causing Genetic Defect in Patient-derived Stem Cells

A potential precision medicine approach for treating vision loss

Columbia University Medical Center (CUMC) and University of Iowa scientists have used a new gene-editing technology called CRISPR to repair a genetic mutation responsible for retinitis pigmentosa (RP), an inherited condition that causes the retina to degrade and leads to blindness in at least 1.5 million cases worldwide.

The study was published in Scientific Reports, and marks the first time researchers have replaced a defective gene associated with a sensory disease in stem cells that were derived from a patient’s tissue.

Our vision is to develop a personalized approach to treating eye disease,” says Stephen Tsang, MD, PhD, the László Z. Bitó Associate Professor of Ophthalmology and associate professor of Pathology & Cell Biology at CUMC, ophthalmologist at NewYork-Presbyterian/Columbia, and one of the study’s senior authors. “We still have some way to go, but we believe that the first therapeutic use of CRISPR will be to treat an eye disease. Here we have demonstrated that the initial steps are feasible.”

In the study, the researchers created stem cells from a sample of skin that was taken from a patient with retinitis pigmentosa. As the patient-derived stem cells still harbored the disease-causing mutation, the teams used CRISPR to repair the defective gene. The stem cells can potentially be transformed into healthy retinal cells and transplanted back into the same patient to treat vision loss.

“The X-linked form of retinitis pigmentosa is an ideal candidate for a precision medicine approach because a common mutation accounts for 90% cases,” Tsang explains. Using CRISPR —which is easily adaptable to diverse sequences of DNA, and allows for fast and accurate editing —scientists can take a patient’s own cells and make pinpoint repairs specific to that individual’s genome.

Because the corrections are made in cells derived from the patient’s own tissue, doctors can re-transplant the cells with fewer fears of rejection by the immune system. Previous clinical trials have shown that generating retinal cells from embryonic stem cells and using them for transplantation is a safe and potentially effective procedure.

In this paper, the researchers targeted one of the most common variants of retinitis pigmentosa, which is caused by a single mistake in a gene called RGPR. The composition of RGPR—which contains many repeats and tight-binding nucleotide pairs—make it a difficult gene to edit. The researchers say that preliminary success with RGPR is therefore promising for treating other forms of the condition caused by mutations in other genes.

The current treatment for retinitis pigmentosa recommended by the National Institutes of Health—consuming high doses of vitamin A—slows down vision loss but does not cure the disease.

Other types of gene therapies for retinitis pigmentosa are currently undergoing clinical trials. Unlike CRISPR-based methods, these therapies introduce stretches of DNA that supplement some of the activity of the defective gene, but do not directly correct the original mutation. Follow-up studies have shown that any gains in vision from these gene supplementation therapies wane over time.

A CRISPR-driven precision medicine approach to treating retinitis pigmentosa may improve upon current therapies and restore a patient’s vision because CRISPR, with its pinpoint accuracy, can correct the fundamental genetic defect responsible for the disease. However, CRISPR technology has not yet been approved for use in humans.

Recently, another group has used CRISPR to ablate a disease-causing mutation in rats with retinitis pigmentosa. This study hints at the promise for using CRISPR therapeutically in humans, and the CUMC and Iowa groups are now working to show that the technique does not introduce any unintended genetic modifications in human cells, and that the corrected cells are safe for transplantation.

Tsang and colleagues believe that the first clinical use of CRISPR could be for treating an eye disease because compared to other body parts, the eye is easy to access for surgery, readily accepts new tissue, and can be noninvasively monitored.



The paper is titled, “Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells.” The other contributors are: Andrew Zheng and Yao Li from CUMC, and Alexander G. Bassuk and Vinit B. Mahajan from Iowa University.


The study was funded by grants from the National Institutes of Health (K08EY020530, R01EY024665, R01EY025225, R01EY024698, R01EY018213, R21AG050437, 5P30CA013696 and 5P30EY019007), Doris Duke Charitable Foundation (2013103), Research to Prevent Blindness, Tistou and Charlotte Kerstan Foundation, New York State (C029572), the Foundation Fighting Blindness New York Regional Research Center (C-NY05-0705-0312), Barbara & Donald Jonas,  Michael and Joan Schneeweiss, Jacob & Tamara Pluchenik, Gebroe Family Foundation, Crowley Family Fund and Foundation Fighting Blindness (CF-CL-0613-0614-COLU). Yao Li is a fellow in Irving Center Precision Medicine program at CUMC.


The authors declare no financial or other conflicts of interest.


Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit or




NewYork-Presbyterian is one of the nation’s most comprehensive healthcare delivery networks, focused on providing innovative and compassionate care to patients in the New York metropolitan area and throughout the globe. In collaboration with two renowned medical school partners, Weill Cornell Medicine and Columbia University College of Physicians & Surgeons, NewYork-Presbyterian is consistently recognized as a leader in medical education, groundbreaking research and clinical innovation.


NewYork-Presbyterian has four major divisions: NewYork-Presbyterian Hospital is ranked #1 in the New York metropolitan area by U.S. News and World Report and repeatedly named to the magazine’s Honor Roll of best hospitals in the nation; NewYork-Presbyterian Regional Hospital Network is comprised of leading hospitals in and around New York and delivers high-quality care to patients throughout the region; NewYork-Presbyterian Physician Services connects medical experts with patients in their communities; and NewYork-Presbyterian Community and Population Health features the hospital’s ambulatory care network sites and operations, community care initiatives and healthcare quality programs, including NewYork Quality Care, established by NewYork-Presbyterian, Weill Cornell and Columbia.


NewYork-Presbyterian is one of the largest healthcare providers in the U.S. Each year, nearly 29,000 NewYork-Presbyterian professionals deliver exceptional care to more than 2 million patients.


For more information, visit and find us on Facebook, Twitter and YouTube.