Gene editing protects pigs from killer virus

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Researchers have used gene editing to successfully breed pigs that are resistant to a deadly virus.

Coronaviruses, highly contagious and widespread viruses known for their distinctive microscopic halos, are responsible for a variety of deadly intestinal diseases in livestock. One such virus, Transmissible Gastroenteritis Virus (TGEV), commonly infects the intestines of pigs, causing almost 100 percent mortality in young pigs.

“Previous research had identified an enzyme called ANPEP as a potential receptor for the virus, meaning it could be an important factor in allowing the virus to take hold in pigs,” says Randall Prather, professor of animal sciences in the College of Agriculture, Food, and Natural Resources at the University of Missouri.

“We were able to breed a litter of pigs that did not produce this enzyme, and as a result, they did not get sick when we exposed them to the virus,” he says.

‘Null’ gene

Prather and his colleagues edited the gene responsible for making the ANPEP enzyme, resulting in a litter of seven pigs with a “null” gene that did not produce the enzyme. When exposed to the TGEV virus, the pigs did not become infected, showing that the presence of the ANPEP enzyme is necessary for an infection and gene editing can create pigs that are resistant.

“It’s a tremendous financial burden for farmers to put time, money, and labor into animals that will get sick,” says coauthor Kristin Whitworth, a research scientist in the animal sciences division. “Breeding pigs with genetic resistance will help to ease that burden. In terms of animal welfare, if we can prevent these pigs from getting sick, we have a responsibility to do so.”

In comparison to the scores of gene mutations that occur naturally during the reproductive process, researchers only altered the expression of a single gene. Those pigs lacking the enzyme were healthy and experienced no changes in development.

“The collaboration with Randy and his team has established some of the most rewarding milestones of my career,” says coauthor Raymond “Bob” Rowland, a professor of diagnostic medicine and pathobiology at Kansas State University.

Bigger picture

“Porcine coronaviruses are a global threat to the pig industry. One of the greatest concerns for US producers are outbreaks of new coronaviral diseases. Once again, this work demonstrates the importance of this technology in solving complex disease problems. Genetic modification to protect pigs from endemic and emerging diseases is the future of the pork industry,” Rowland says.

The study follows a similar success achieved in 2015, when researchers made pigs resistant to the deadly and costly Porcine Reproductive and Respiratory Syndrome (PRRS) virus by using gene editing.

The University of Missouri has partnered with Genus plc to commercialize this method of producing virus-resistant pigs, which will improve animal health and well-being and greatly reduce losses in livestock production worldwide due to viral infections, making global pig farmers more sustainable. Genus plc is currently seeking FDA approval for the use of gene editing technology for use in eradicating the PRRS virus.

The study also sought to determine whether editing out ANPEP would produce resistance to Porcine Epidemic Diarrhea Virus, which killed nearly 7 million pigs in a 2013 outbreak. While pigs lacking the enzyme still contracted the virus, researchers are optimistic that the study bodes well for future research.

“With ANPEP eliminated, we can focus on a smaller field of potential culprits,” says coauthor Kevin Wells, associate professor of animal sciences. “In this area of research, every step helps.”

The study appears in Transgenic Research.

Additional researchers involved in the study are from the University of Missouri, Kansas State University, and Genus plc. Genus plc and the Kansas NBAF provided funding for the study.

Source: University of Missouri