Using a new, versatile form of CRISPR-based genome editing, researchers in China have effectively restored the vision of mice afflicted with retinitis pigmentosa, a serious cause of blindness in people. The findings of the study, published on March 17 in the Journal of Experimental Medicine, reveal that this new gene-editing technique has the potential to correct a broad range of disease-causing genetic mutations.
In the past, researchers utilized genome editing to recover vision in mice that suffer from genetic diseases like Leber congenital amaurosis. These diseases affect the retinal pigment epithelium, which is a layer of non-neuronal cells that help the rod and cone photoreceptor cells that sense light. But, the majority of hereditary blindness types, including retinitis pigmentosa, occur due to genetic abnormalities in the neural photoreceptor cells themselves.
"The ability to edit the genome of neural retinal cells, particularly unhealthy or dying photoreceptors, would provide much more convincing evidence for the potential applications of these genome-editing tools in treating diseases such as retinitis pigmentosa," says Kai Yao, a professor at the Wuhan University of Science and Technology.
Yao and colleagues aimed to restore the vision of mice that had retinitis pigmentosa due to a mutation in the gene responsible for encoding the essential enzyme, PDE6β. They accomplished this by creating a new CRISPR system called PESpRY, which is more adaptable and can correct various types of genetic mutations throughout the genome.
By targeting the mutant PDE6β gene, the PESpRY system could effectively correct the mutation and recover the enzyme's activity within the retinas of mice. This prevented the demise of rod and cone photoreceptors and re-established their typical electrical responses to light.
Yao and colleagues conducted several behavioral examinations to verify that the vision of the gene-edited mice remained intact even as they aged. The researchers administered a visually guided water maze test and discovered that the mice could navigate it nearly as well as healthy, normal mice. Additionally, the animals exhibited typical head movements in response to visual stimuli.
Although the PESpRY system has demonstrated positive outcomes in mice, Yao warns that more research is necessary to validate its safety and effectiveness in humans. Nonetheless, Yao believes that their study has provided substantial evidence for the practicality of this gene-editing strategy in vivo and its potential in various research and therapeutic settings, particularly for inherited retinal diseases such as retinitis pigmentosa.
Huan Qin et al, Vision rescue via unconstrained in vivo prime editing in degenerating neural retinas, Journal of Experimental Medicine (2023). DOI: 10.1084/jem.20220776