“See how they run. See how they run. They all run after the farmer’s wife …,” is how the old song goes about the trio of visually impaired rodents. Well, science may soon have a solution to their acuity troubles through the use of gene-editing techniques. In a new study, researchers at the Cedars-Sinai Board of Governors Regenerative Medicine Institute have been able to hinder retinal degeneration in an inherited form of blindness called retinitis pigmentosa (RP). While the current study was performed in rats, the speed at which the gene-editing technique CRISPR is being adopted by researchers as a viable therapeutic tool, it won’t be long before mice are actually able to see the farmer’s wife as they chase after her.
Inherited RP is a degenerative eye disease that can lead to blindness and has no known cure. The Cedars-Sinai scientists utilized the CRISPR/Cas9 system to remove a genetic mutation that causes the disease. The results of this study could have important implications for human therapy in the near future.
“Our data show that with further development, it may be possible to use this gene-editing technique to treat inherited retinitis pigmentosa in patients,” explained senior study author Shaomei Wang, M.D., Ph.D., associate professor of biomedical sciences and researcher scientist at the Cedars-Sinai Board of Governors Regenerative Medicine Institute’s eye program.
The findings from this study were published recently in Molecular Therapy through an article entitled “In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa.”
Typically, patients with RP experience night blindness in the early stages, along with atrophy and pigment changes in the retina, constriction of the visual field, and eventual blindness. The disease is relatively rare overall, but does constitute one of the most common inherited diseases of the retina in humans, affecting about 1 in 4,000 people in the Unites States and Europe.
In the current study, the investigators designed a CRISPR/Cas9 system to remove a mutated gene that causes photoreceptor cell loss in the eye. They injected this system into young laboratory rats with the autosomal dominant form of the disease. After a single injection, the treated rats were able to see better compared to untreated controls.
“As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (RhoS334) in rats that model severe autosomal dominant Retinitis Pigmentosa (adRP),” the authors wrote. “A single subretinal injection of guide RNA (gRNA)/Cas9 plasmid in combination with electroporation generated allele-specific disruption of RhoS334, which prevented retinal degeneration and improved visual function.”
The scientists were excited by their findings and feel that, with some tweaking of the CRISPR modifying elements and possibly the use of a new viral delivery system, the efficacy of their results should improve.
“This is the first time CRISPR/Cas9 gene editing has been used to prevent vision loss in a living animal,” noted co-author Clive Svendsen, Ph.D., director of the Board of Governors Regenerative Medicine Institute. “It is a truly remarkable result and paves the way for more exciting studies and translation to the clinic in the future.”