New gene editing technique repairs retinitis pigmentosa mutation

Scientists have successfully used CRISPR gene editing technology to fix a genetic defect that causes retinitis pigmentosa.

Researchers from Columbia University Medical Center and University of Iowa took a skin sample from a patient with a single mutation in the RPGR gene, and used an established method to generate induced pluripotent stem cells (iPSCs) from the skin fibroblasts.  Investigators then used new gene-editing technology –  based on the bacterial system of clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9 – to target, edit out and replace the mistake in RPGR.

The authors corrected the mutation with a 13% success rate, much higher than the 1% rate achieved with other platforms. These embryonic-like stem cells have the potential to differentiate into healthy retinal cells and can be transplanted back into the same patient without any need for immunosuppressive medication.

The specificity of CRISPR depends largely on a guide RNA that can be programmed to target different genomic loci, allowing for fast, accurate DNA editing. Other types of gene therapies for retinitis pigmentosa are currently undergoing clinical trials; however, these therapies are aimed at supplementing some of the activity of the defective gene rather than directly correcting the original mutation. Follow-up studies have shown that visual gains from these gene supplementation therapies wane over time.

While challenges remain, the authors conclude that CRISPR/Cas9 technology is moving toward potential clinical development to treat retinal disease.

The eye is an ideal place to begin clinical use of CRISPR, as it is easily accessible for surgery, readily accepts new tissue and can be noninvasively monitored. Scientists are evaluating its potential in a number of ophthalmic diseases, including corneal dystrophies, Leber hereditary optic neuropathy and MYOC-associated glaucoma.