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.

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.

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 a 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.

http://newsroom.cumc.columbia.edu/blog/2016/01/27/crispr-used-repair-blindness-causing-genetic-defect-patient-derived-stem-cells/