CRISPR-based genome editing restores vision in mice with retinitis pigmentosa

Researchers in China have succeeded in restoring the vision of mice with retinitis pigmentosa, which is one of the main causes of blindness in humans. The study, to be published March 17 in the Journal of Experimental Medicineuses a new, versatile form of CRISPR-based genome editing with the potential to correct a wide range of disease-causing genetic mutations.

Researchers have previously used genome editing to restore vision in mice with genetic diseases, such as Leber’s congenital disease, that affect the retinal pigment epithelium, a layer of non-neuronal cells in the eye that supports light-sensing neurons and cone photoreceptor cells. . However, most forms of inherited blindness, including retinitis pigmentosa, are caused by genetic defects in the nerve photoreceptors themselves.

The ability to edit the genome of neuronal retinal cells, especially unhealthy or dying photoreceptors, will provide even more compelling evidence for the potential applications of these genome editing tools in the treatment of diseases such as retinitis pigmentosa.

Cai Yao, a professor at Wuhan University of Science and Technology

Retinitis pigmentosa can be caused by mutations in more than 100 different genes and is estimated to impair the vision of 1 in 4,000 people. It begins with the dysfunction and death of dim-light-sensing rod cells, before spreading to the cone cells needed for color vision, eventually resulting in severe and irreversible loss of vision.

Yao and his colleagues attempted to rescue the vision of mice with retinitis pigmentosa caused by a mutation in a gene that encodes an important enzyme called PDE6β. To do this, Yao’s team developed a new, more versatile CRISPR system called PE^Interestingwhich can be programmed to correct many different types of genetic mutations, regardless of where they occur within the genome.

When programmed to target the mutant PDE6β gene, PE^Interesting The system was able to efficiently correct the mutation and restore enzyme activity in the rat retina. This prevented the death of cone and rod photoreceptors and restored their normal electrical responses to light.

Yao and his colleagues conducted a variety of behavioral tests to confirm that the genetically modified mice retained their vision even into old age. For example, the animals were able to find their way out of a visually-guided water maze nearly as well as normal, healthy mice and showed typical head movements in response to visual stimuli.

Yao warns that there is still a lot of work to be done to prove safety and effectiveness PE^Interesting system in humans. “However, our study provides substantial evidence of the in vivo applicability and potential of this novel genome editing strategy in diverse research and treatment contexts, particularly for inherited retinal diseases such as retinitis pigmentosa,” Yao says.