ARVO 2015 Highlight: A Cut-and-Paste Approach to Fixing Retinal-Disease Genes

I just returned from the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), the world's largest eye-research conference, held this year in Denver. It attracted more than 11,000 scientists and physicians, including many of the 187 retinal researchers funded by the Foundation. The FFB science team and I worked feverishly to learn as much as possible about the latest news from the retinal-research front. It was truly exhilarating—albeit, at times, overwhelming.

One of the hot topics at ARVO this year is a rapidly advancing gene-therapy approach called clustered regularly interspaced short palindromic repeats, or CRISPR. Given that name doesn't exactly roll off one's tongue, it's usually just called "crisper," as in, "Honey, something in the fridge smells awful. I think the cabbage in the crisper is rotting."

CRISPR is different from the gene therapies currently in human studies, which involve gene replacement—i.e., delivering copies of a whole new normal gene to replace the defective copies causing vision loss. In contrast, CRISPR is a gene "cut-and-paste" technology. It works like a molecular scissors to cut out the mutated portion of the gene and inserts a healthy piece of DNA.

Think of it this way: Let's say your car won't start. You have two options: Buy a new car or fix the part that's causing the problem. Getting a new car is like gene replacement. Getting a new part to fix the problem—for example, a battery, starter or fuel pump—is like CRISPR.

Both CRISPR and gene replacement have their pros and cons. One big advantage of CRISPR is getting around the problem of delivering large genes—USH2A, for example—that won't fit in the human-made viruses designed to carry them into retinal cells.

Also, CRISPR may be a simpler approach to treating diseases in which delivering a whole new gene is not necessary, and simply shutting down or repairing the bad gene may be enough to save vision. This is often the case in autosomal dominant retinitis pigmentosa.

The downside to CRISPR, at least at the moment, is that it often doesn't work efficiently enough to restore vision. Also, it can have unwanted, off-target effects on healthy genes. But progress in overcoming these issues was reported at ARVO, so scientists are getting closer to moving CRISPR gene therapy into the clinic.

Several scientists presented compelling CRISPR research projects at ARVO this year. Ed Stone, M.D., Ph.D., a Foundation-funded investigator at the University of Iowa, gave a nice presentation on how his team used different CRISPR approaches on cells in the lab to correct the retinal disease genes USH2A, MAK and RHO. And they are working on more.

I suspect that, down the road, there will be a role for both gene replacement and CRISPR (and related gene-editing approaches). It will be interesting to see how these alternatives evolve and mature. Given the diversity and complexity in gene mutations that can cause retinal disease, the more options, the better.