At the Roslin Institute at the University of Edinburgh, the animal research center where Dolly the sheep was created, they have used gene editing to breed chickens that are resistant to bird flu infection. This virus, deadly to birds, which causes major economic losses worldwide and can infect and kill humans in some cases, has proven elusive to vaccines because it rapidly alters the proteins on its surface that the system recognizes. immune. A group of British researchers, publishing their findings today in the journal Nature Communications, have tested the potential of altering small sections of chicken DNA to prevent flu infection, even if only partially.
Influenza A requires a protein from chicken cells, ANP32A, to replicate. The team of scientists, led by Mike McGrew, a researcher at the University of Edinburgh, used the CRISPR editing technique to modify the gene that produces the protein in the germ cells of chickens, allowing them to pass the change on to their offspring. In this way, animals were created that were unlikely to become infected with the flu when in contact with other infected birds (only 9 out of 10) and did not subsequently infect other chickens. In a later test, in which they were vaccinated with a dose a thousand times higher, five out of ten became infected.
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The authors explain that the virus adapted to the change and began using two other proteins from the same family (ANP32B and ANP32E) to continue replicating, albeit with lower efficiency. This led the authors to attempt to alter two additional genes to stop the virus from progressing in the eggs. Although they did not allow chickens to grow with this triple requirement, the authors believe it would have deleterious side effects on the animals’ fertility, their ability to gain weight, or protection against other diseases, making practical use impossible. Nevertheless, they consider it a proof of concept that it is possible to use this technique to protect against influenza A infection.
Lluis Montoliu, a geneticist at the National Center for Biotechnology of the CSIC, who did not take part in the study, sees the result as an announcement of a future in which “animals can be produced that are resistant to influenza infections, which is no longer necessary” but several genetic changes.” . “A few years ago it would have been quite challenging to create more than one modification in the same animal,” he explains. “It’s much easier now with CRISPR gene editing tools,” he adds. As the researcher explains, these techniques make it possible to transfer “mutations that already occur in nature,” since “there are flu-resistant chickens with two mutations in ANP32A,” “to the production of edited birds.” “We use the existing genetic Variability to create resistance,” he summarizes.
In addition to being able to introduce protective mutations without creating less productive animals, the researchers also want to ensure that their changes don’t push a virus as versatile as the flu in dangerous directions. When their ANP32A protein was removed, the viruses adapted to use proteins from the same family found in humans. According to Wendy Barclay, a researcher at Imperial College London and co-author of the paper, “This doesn’t mean it could infect people, but we need to be careful not to enable adaptations to the virus that make it more dangerous than it is.”
Once the problems and risks of editing were overcome, practical application, McGrew recognized, had to overcome other difficulties. “About 70 billion chickens are produced every year. To reach this number, you start with about 100,000 at the top of a reproductive pyramid and expand it over four years. “You would start by editing the animals at the top so that they then reproduce and pass on the resistance to their offspring,” he explains. “But chickens are not like other animals where one male mates with 100 females. It’s more like 100/100 and it will be difficult to get that much spending going,” he admits.
Víctor Briones, researcher at the Veterinary Health Surveillance Center of the Complutense University of Madrid, considers it “an interesting proof of concept,” but believes that its application is only possible “in industrial poultry farming.” Also remember: “The large reservoirs [de la gripe aviar] They are the ducks [aves, habitualmente migratorias, de la familia de los patos]“. Although introducing these types of genetic changes to wild birds appears to be difficult, McGrew points out that the three altered genes “are conserved across all bird species and this editing should work in any species.” Even with domestic chickens, special changes would have to be made due to the large variety of varieties. The authors are now working to solve these and other problems to turn an interesting scientific paper into a practical solution.
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