Science

Animals less susceptible to epidemics thanks to genome editing

For English biologists, Brexit will have at least had a positive effect. Prime Minister Boris Johnson is expected to ease regulations on genomic editing in animals during June. This decision – which also concerns plants – will allow our neighbor to move faster than the rest of Europe towards the production and marketing of species whose DNA has been voluntarily modified. In France, some scientists do not hide their frustration. Because on this side of the Channel, the legal brakes remain tight, despite promising avenues of research.

“In terms of genome modification, the The general public is especially familiar with GMOs: by a technique known as transgenesis, researchers are able to insert a piece of DNA fragment from one species into that of another. Either to make it grow faster, or to make it more resistant to herbicides or diseases, as in the most publicized examples in plants, “recalls Hervé Acloque, molecular biologist in the Animal Genetics department of the National Institute of research for agriculture, food and the environment (INRAE) in Jouy-en-Josas. Genomic editing works differently: based on Crispr-Cas9 technology, the famous molecular scissors, it allows to target very precisely a gene or site on an organism’s genome and modify it, without using or inserting foreign DNA.

“A molecule serves as a guide. It will specifically recognize the region that we want to modify, then an enzyme will do the work”, explains Xavier Montagutelli, geneticist and director of a mouse genetics laboratory at the Institut Pasteur . “Compared to GMO technologies, it is an extremely precise intervention,” hand-sewn “, details” Edwige Quillet, head of the animal genetics department at INRAE.

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Pigs insensitive to respiratory distress syndrome

By changing the genetic code at the margin, researchers are able to influence certain “characters”, such as resistance to certain viruses. The technique is still a little crude: it consists in removing the receptor from certain cells in order to prevent the virus from attaching to it. For example, a team from the Roslin Institute in Edinburgh (Scotland) recently succeeded in producing pigs insensitive to PRRS (porcine respiratory distress syndrome). “Let’s be clear, transgenesis continues to render invaluable services in basic research. Used in mice, for example, it allows researchers to assess the effectiveness of vaccines against the coronavirus. However, the editing is proving to be precise and above all, it quickly creates mutations that could occur naturally, over generations. In other words, it saves a lot of time compared to the selection practiced by breeders, “Judge Xavier Montagutelli.

“This is an extremely promising technique for the prevention of infectious diseases. Think of foot-and-mouth disease, or African swine fever. The latter, for which there is no cure or vaccine, can lead to eradication. millions of animals The World Organization for Animal Health lists more than 50 diseases affecting animals that can have serious consequences for the health of domestic livestock and / or public health. really be the prophylaxis of the major zoonotic diseases of the 21st century “, concludes Michel Thibier, veterinary doctor, specialist in animal reproduction biotechnologies and honorary professor at AgroParisTech.

Its use would not only limit the foci of infection, but at the same time reduce the production of antibiotics. Applied to cattle, genome editing could also make dehorning practices obsolete and, why not, facilitate the adaptation of certain species to climate change. At least in theory.

“On paper, there are many possible applications. In practice, it is a little more complicated: the techniques remain difficult to implement. We do not immediately achieve the expected result. Several generations may be necessary. to obtain the desired individuals. Finally, to modify a character by genomic editing, it is necessary to know the genes, sometimes very numerous, which control its expression and among these, those which it would be most interesting to modify. ‘does not always exist “, observes Edwige Quillet. Sometimes certain unwanted changes – referred to as off target – appear. This is the case, for example, when the guide molecule has not been designed with sufficient rigor, or when in the genome, by chance, some sequences resemble those that we target. “We still lack perspective on the possible induced effects”, recognizes Hervé Acloque. Thus, suppressing a cell receptor on an animal is not trivial. “A genome can be seen as a ribbon that carries a succession of information interacting with each other. It is a complex network. When you push something aside in one place, necessarily, you push things up a bit,” analyzes Edwige Quillet.

“It is true that there is a lack of fundamental knowledge, but this can precisely be acquired through an intensive investment in research. Provided, however, that the legislation allows it. However, for the moment, this is not the case “, regrets Michel Thibiet. From a legal point of view, the production and use for scientific purposes of animals whose genome has been edited is doubly regulated. Protocols are only authorized after review by an ethics committee in animal experimentation. The regulations on the use of genetically modified organisms also apply, with an opinion from the High Council for Biotechnologies “, details Edwige Quillet.” The problem is that, currently, the law puts GMOs and genomic editing in the same bag. Whereas the latter, on a molecular level, brings about modifications that are indistinguishable from a natural process. Ultimately, researchers don’t want to work on editing animals. They know very well that the regulations will block all outlets, ”denounces Xavier Montagutelli.

France late

“There is a lot of reluctance on this subject. Our leaders fear rejection from part of the population, as we have seen on GMOs. However, we are in the process of falling considerably behind, warns Michel Thibier. In other countries such as China, the United States, the United Kingdom (now outside the European Union) or Canada, research is progressing because it benefits from a much more favorable framework. English have already produced pigs insensitive to a viral disease, very contagious, called PRRS over several generations.If Europe proves unable to invest, we may be condemned tomorrow to buy embryos edited in these countries.

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“We are not asking to create animals modified in series. It is a question of authorizing some tests intended to protect certain species with regard to pathogens for which we have no vaccine solution”, pleads Jean- Pierre Jégou, President of the Veterinary Academy of France. “This research would be carried out in a controlled framework: animals monitored and perfectly identified, with the possibility of interrupting the work if necessary “, continues the veterinarian who deplores a lack of openness on the side of the European Commission. “Genomic editing is not a miracle cure. Editing will not be used systematically to treat all infectious diseases, adds Xavier Montagutelli. It would not make sense. Certain diarrhea – of calf for example – will continue to be treated with antibiotics. But should we deprive ourselves of this tool which can be very relevant in certain cases? It would be a shame, “said the scientist.

This would also penalize other types of research. “We are focusing on editing the bases of DNA. But thanks to the Crispr-Cas9 tools, we discovered that we could modify many other things, says Hervé Acloque. For example, editing RNAs would allow modulating phenotypes without modifying the sequence of the genome. It is also possible to modify certain proteins, or certain layers of information which are present on the molecule on DNA, but which are not part of it. By following these different avenues, one day we may be able to improve the resistance of animals to certain viruses or bacteria “. But for now, urge another researcher, “the risk is rather to see all these ideas nipped in the bud”.


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