Vision restored in mice with retinitis pigmentosa thanks to gene editing

Good news! Wuhan has more to offer than SARS-CoV-2/Covid-19! 😊

"... Now, researchers at the Wuhan University of Science and Technology in China have refined the CRISPR tool into a system they call PESpRY. They used it to fix a mutated gene responsible for encoding an enzyme called PDE6β.
Once the mutation was repaired, the gene went back to encoding the enzyme – this action prevented the death of rod and cone cells, which is the process by which retinitis pigmentosa causes blindness. After the enzyme was being properly produced again, the mice regained their sight as verified through head-turning tests as well as successful completion of a visually guided water maze puzzle. The research team verified that the restored vision remained even into the animals' old age. ...
While it ... affects about 1 in 5,000 people worldwide, retinitis pigmentosa is the most commonly inherited disease of the retina, so research seeking a cure across a variety of modalities is ongoing. ..."

"Researchers in China have successfully restored the vision of mice with retinitis pigmentosa, one of the major causes of blindness in humans. The study, to be published March 17 in the Journal of Experimental Medicine, uses a new, highly versatile form of CRISPR-based genome editing with 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, such as Leber congenital amaurosis, that affect the retinal pigment epithelium, a layer of non-neuronal cells in the eye that supports the light-sensing rod and cone photoreceptor cells. However, most inherited forms of blindness, including retinitis pigmentosa, are 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. ..."

From the abstract:

"Retinitis pigmentosa (RP) is an inherited retinal dystrophy causing progressive and irreversible loss of retinal photoreceptors. Here, we developed a genome-editing tool characterized by the versatility of prime editors (PEs) and unconstrained PAM requirement of a SpCas9 variant (SpRY), referred to as PESpRY. The diseased retinas of Pde6b-associated RP mouse model were transduced via a dual AAV system packaging PESpRY for the in vivo genome editing through a non-NGG PAM (GTG). The progressing cell loss was reversed once the mutation was corrected, leading to substantial rescue of photoreceptors and production of functional PDE6β. The treated mice exhibited significant responses in electroretinogram and displayed good performance in both passive and active avoidance tests. Moreover, they presented an apparent improvement in visual stimuli-driven optomotor responses and efficiently completed visually guided water-maze tasks. Together, our study provides convincing evidence for the prevention of vision loss caused by RP-associated gene mutations via unconstrained in vivo prime editing in the degenerating retinas."

Vision restored in mice thanks to refined CRISPR system

New gene-editing technique reverses vision loss in mice

Vision rescue via unconstrained in vivo prime editing in degenerating neural retinas (open access)

Figure 8 The impaired vision is restored in the individual eyes and in aged Pde6b rd10 mice treated with PE SpRY system and gPde6b