By the age of four months, the retinas of mice carrying a mutation in the gene encoding PDE6β (left) are thin and lack rod photoreceptors (red). But mice who have had this mutation corrected through the PESpRY system (right) have much thicker retinas containing numerous rod cells. Credit: © 2023 Qin et al. Originally published in Journal of Experimental Medicine. https://doi.org/10.1084/jem.20220776
Key points:
- Researchers developed and used a new genome editing system to restore vision in mice.
- The CRISPR-based system can be programmed to correct many different types of genetic mutation.
- In tests, it restored vision in mice with retinitis pigmentosa, which impairs the vision of 1 in 4,000 people.
In a study published in the Journal of Experimental Medicine, researchers in China documented the successful restoration of vision in mice with retinitis pigmentosa, a leading cause of blindness in humans. The researchers used a new, highly versatile form of CRISPR-based genome editing that has the potential to correct a wide variety of disease-causing genetic mutations.
Researchers have previously used genome editing to restore the vision of mice with genetic diseases that that affect the retinal pigment epithelium; but, this didn’t address more common inherited forms of blindness—including retinitis pigmentosa, which is caused by genetic defects in the neural photoreceptors themselves.
Retinitis pigmentosa can be caused by mutations in over 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 required for color vision, eventually leading to severe, irreversible vision loss.
Researchers at Wuhan University of Science and Technology wanted to focus on a mutation in the gene encoding a critical enzyme called PDE6β. But to access the gene, they first needed to create a new, more versatile CRISPR system. PESpRY, as Kai Yao and his team named the system, can be programmed to correct various forms of genetic mutation, regardless of where they occur within the genome.
In tests, the PESpRY system was able to efficiently target and correct the mutant PDE6β gene and restore the enzyme’s activity in the retinas of mice. It prevented the death of rod and cone photoreceptors and restored their normal electrical responses to light.
Yao and his team performed a variety of behavioral tests that confirmed the mice treated with the PESpRY retained their vision even into old age.
“Our study provides substantial evidence for the in vivo applicability of this new genome-editing strategy and its potential in diverse research and therapeutic contexts, in particular for inherited retinal diseases such as retinitis pigmentosa,” said Yao.