2023-10-31 19:30:10
British researchers wanted to make laying hens resistant to a strain of the bird flu virus using the new genetic engineering process Crispr/Cas, they recently reported in the journal Nature Communications. But the viruses quickly overcame resistance and mutated in such a way that they might also pose a threat to humans. It is clear to the study authors that these chickens are not suitable for agriculture. An uninvolved scientist called the experiments an “academic finger exercise.”
To multiply, the bird flu virus uses a protein called ANP32A in animals. The researchers from Edinburgh’s Roslin Institute and Imperial College London used Crispr/Cas to change the gene responsible for the production of ANP32A. The ANP32A protein then produced contained two other amino acids and might no longer be abused by the viruses to reproduce . Experiments with these Crispr chickens showed that nine out of ten chickens did not become infected when the viral load was low. However, when the viral load of the H2N9 strain was increased 1,000-fold, half of the animals became ill. Some of the viruses had mutated and learned to use the related proteins ANP32B and ANP32E to multiply. In the laboratory, the researchers also discovered that these mutants were also able to “unexpectedly” multiply in cells of the human respiratory tract and use the shorter human ANP32 proteins to do this.
“However, that does not mean that modified bird flu viruses have emerged that can trigger a new pandemic,” explained the reporter for the Neue Zürcher Zeitung, who is herself a molecular biologist. “However, if the modified viruses continue to exist and spread in the real world, then it is not impossible that they will continue to mutate – and that a pandemic virus will emerge at some point.” The Spanish flu emerged in a similar way 100 years ago. The researchers are aware of this risk, wrote NZZ author Stephanie Lahrtz. That’s why they emphasized to journalists that it was impossible for the Crispr chickens they produced to ever be used on farms.
In order to rule out the risk of a pandemic, the researchers next created chickens that no longer produced ANP32A, but this only limited the mutated viruses slightly. Finally, for laboratory experiments, they created chicken cells that lacked all three ANP32 proteins. Neither the original virus nor the mutations replicated in these cells. There were also no breakthrough infections, the researchers wrote, but admitted that “this combination of knockouts is likely to be harmful to the health of the animals” and nothing would have been gained “if the increased resistance to bird flu was accompanied by a loss of fitness birds”. To check this, they now want to develop living chickens without ANP32 proteins following these cell experiments.
Timm Harder, bird flu expert at the state-run Friedrich Loeffler Institute for Animal Health, explained to the Science Media Center the legal situation if such genetically engineered animals were actually used: According to European law, these are chickens whose genome has been changed using Crispr/Cas , to be considered as genetically modified organisms. “Their use would therefore require genetic engineering approval and, according to current law, keeping them would only be possible in a genetic engineering facility. Free-range farming would then be equivalent to a release project.” The laws would therefore have to be adapted accordingly for mass use. But first, long-term experiments would have to show what effects the switched off genes would have on the chickens. It also remains to be seen “how these chickens will behave once morest the much more aggressive, highly pathogenic avian influenza viruses such as H5N1; these were not tested here.” H5N1 is the currently rampant bird flu virus; the British researchers used the less aggressive variant H2N9.
The virologist Stephan Ludwig from the University of Münster described the “elegant work” to the Science Media Center as a “proof of concept”, i.e. a feasibility study that showed “that a gene editing strategy can be suitable for a to achieve robust resistance to infection”. At the same time, however, the enormous adaptability of the viruses became clear, “which led to breakthrough infections even in these first experiments at high viral loads.” In addition to the rapid adaptation of the viruses, Ludwig also sees “legal and ethical hurdles” as well as the problem of a lack of acceptance. “In this respect, the work is initially an elegant academic exercise and is still far from being used in actual practice,” was his conclusion. [lf]
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