Gene therapy for the first time saved the mouse from blindness

Biologists from the US first used the genomic editor CRISPR / Cas9 to “repair” DNA in the cells of the mouse’s retina and remove the gene associated with the development of complete blindness.

“Our past experiences have shown that we can avoid the development of blindness in such animals if we remove the Nrl gene in retinal cells that will make the sticks turn into cells that are similar in shape to cones, which will save both” former “sticks and neighboring ones Real cones from destruction in the future, “explains Anand Swaroop of the National Eye Institute in Bethesda, USA.

The eyes of people and many other mammals contain two types of photosensitive cells – cones and rods. The cones allow us to distinguish colors, but they only work when the illumination is sufficiently high, and the sticks allow us to see the silhouettes of objects in the dim light of stars or the moon.

According to Swarup, the rods, in addition to the work of “night vision”, play another important role – they support and nourish the remaining cells of the retina, and their destruction irreversibly leads to the death of cones and the entire retina as a whole. Most of the mutations associated with loss of vision, usually strikes the sticks, and if they are available, people usually lose first night vision, and then the ability to see the world and in daylight.

Experiments on embryos, which Swarup and his colleagues conducted in the past, showed that the process of growth of rods and cones is controlled in fact by one gene – Nrl. If this gene is removed during the formation of the embryo, a retina appears, the cones in which do not die, despite the absence of rods.

Scientists have suggested that removing this gene in retinal cells in an adult animal will lead to similar consequences. Guided by this idea, biologists created a retrovirus based on the popular genomic editor CRISPR / Cas9, which infected only the sticks and removed the Nrl gene from their DNA.

The work of this gene therapy was tested by biologists on three groups of mice in whose DNA different mutations were found leading to destruction of the rods and degeneration of the retina. As these experiments showed, the removal of the gene did indeed lead to the transformation of rods into cone analogs, and this transformation stopped the destruction of the retina.

In the end, the mice lost the ability to see in the dark, since all their wands were disabled, but they did not lose sight during the day. As biologists note, gene therapy worked even in the treatment of the eyes of very elderly mice, although it was less effective than in infecting the retina of young individuals.

The main advantage of this strategy of combating blindness, as noted by scientists, is that it allows you to stop the destruction of the retina, regardless of which gene is broken in the sticks, since the removal of Nrl “disconnects” all these sections of DNA.

Clinical trials of this gene therapy, despite its promise, may not begin soon because of the discussions around CRISPR / Cas9. The safety of this genomic editor for medical use is not yet confirmed in practice, and its use to edit the fetal DNA in China has engendered fierce debate among scientists over the past few months.