For the first time, US biologists have used the CRISPR / Cas9 genomic editor to repair DNA in mouse retinal cells and remove a gene associated with the development of total blindness, according to an article published in the journal Nature Communications.
“Our past experiments have shown that we can avoid the development of blindness in such animals if we remove the Nrl gene from the cells of the retina, which causes the rods to turn into cells that are similar in shape to cones. This will save both the “former” rods and their neighboring real cones from destruction in the future,”explains Anand Swaroop from the National Eye Institute in Bethesda, USA.
The eyes of humans and many other mammals contain two types of light-sensitive cells - cones and rods. Cones allow us to distinguish colors, but they only work in high enough light, and rods allow us to see the silhouettes of objects in the dim light of the stars or the moon.
According to Swarup, rods, in addition to working "night vision", play another important role - they support and nourish the rest of the retinal cells, and their destruction irreversibly leads to the death of the cones and the entire retina. Most of the mutations associated with vision loss usually affect the rods, and if they are present, a person usually loses first night vision, and then the ability to see the world in daylight.
Experiments on embryos that Swarup and his colleagues have conducted in the past have shown that actually one gene, Nrl, controls the growth of rods and cones. If this gene is removed during the formation of the embryo, then a retina appears, in which the cones do not die, despite the absence of rods.
Scientists hypothesized that removing this gene from retinal cells in an adult animal would have similar consequences. Guided by this idea, biologists created a retrovirus based on the popular genomic editor CRISPR / Cas9, infecting only rods and removing the Nrl gene from their DNA.
Biologists tested the work of this gene therapy on three groups of mice, whose DNA contained different mutations, leading to the destruction of rods and degeneration of the retina. As these experiments showed, the deletion of the gene actually led to the transformation of rods into analogs of cones, and this transformation stopped the destruction of the retina.
Ultimately, the mice lost their ability to see in the dark, as all of their rods were disabled, but did not lose sight during the day. According to biologists, gene therapy worked even in treating the eyes of very elderly mice, although it was less effective than when infecting the retinas of young individuals.
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The main advantage of this strategy to combat blindness, as scientists note, is that it allows you to stop the destruction of the retina, regardless of which gene is broken in the rods, since removing Nrl "turns off" all these DNA regions.
Clinical trials of this gene therapy, despite its promising potential, may not start soon due to discussions around CRISPR / Cas9. The safety of this genomic editor for medical use has not yet been confirmed in practice, and its use for editing embryonic DNA in China has generated fierce debate among scientists over the past several months.