Chinese researchers have used a CRISPR-based gene editing technique for restore vision in mice with retinitis pigmentosa, one of the main causes of blindness in humans. Retinitis pigmentosa is a genetic disease that can be caused by mutations in more than 100 different genes and it is estimated that one in 4,000 people suffer from it. Alterations in these genes prevent the proper functioning of the retinal cells called rods –which are sensitive to dim light– and cones –which allow color vision–, causing a progressive and irreversible loss of vision.
These scientists had previously used their novel method to edit the genome and had managed to restore sight to mice with genetic pathologies, such as Leber’s congenital amaurosis, which affects the retinal pigment epithelium, a layer of non-neuronal cells in the eye. that supports the light-sensitive rod and cone photoreceptor cells, but the origin of most of the hereditary forms of blindnessincluding retinitis pigmentosa, is found in genetic defects of the neural photoreceptors themselves.
“The ability to edit the genome of neural retinal cells, particularly diseased or dying photoreceptors, would provide much more compelling evidence for the potential applications of these genome-editing tools in the treatment of diseases such as retinitis pigmentosa.” says Kai Yao, a professor at the Wuhan University of Science and Technology.
Gene editing to correct hereditary retinal diseases
The aim of the research was to restore vision in mice with retinitis pigmentosa caused by a mutation in the gene that encodes a key enzyme called PDE6β. To do this, the team led by Yao developed a new, more versatile CRISPR system called PE SpRY, which can be programmed to correct many different types of gene mutations, regardless of where they occur in the genome.
“Our study provides substantial evidence of the in vivo applicability of this new genome editing strategy and its potential in hereditary retinal diseases such as retinitis pigmentosa.ia”
When they programmed the PE SpRY system to target the mutant PDE6β gene, they were able to efficiently correct the mutation and restore enzyme activity in the retinas of mice, thus preventing rod and cone photoreceptor death and restoring their normal electrical responses. to the light.
The researchers performed various behavioral tests to confirm that the mice they had genetically modified continued to maintain vision even into old age. For example, rodents were able to find their way out of a visually guided water maze almost as well as normal, healthy mice, and their head movements in response to visual stimuli were typical in these cases. The findings have been published in Journal of Experimental Medicine.
Yao acknowledged that further research is needed to determine both the safety and effectiveness of the PE SpRY System in people. “However, our study provides substantial evidence of the applicability live of this new genome editing strategy and its potential in various therapeutic and research contexts, particularly for hereditary retinal diseases such as retinitis pigmentosa”, he concludes.