Gene-edited pigs are resistant to TGEV

A team of researchers from the University of Missouri, Kansas State University and Genus plc has succeeded in producing pigs that are resistant to Transmissible gastroenteritis virus (TGEV) by means of gene editing. Their study is published in Transgenic Research.

“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,” said Randall Prather, from the Division of Animal Sciences 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.”

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

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,” said Raymond “Bob” Rowland, a professor of diagnostic medicine and pathobiology at Kansas State University and co-author on the study. “Porcine coronaviruses are a global threat to the pig industry. One of the greatest concerns for U.S. 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.”

This study follows a similar success achieved in 2015, when pigs were made resistant to Porcine reproductive and respiratory syndrome virus (PRRSV) by using gene editing. The University of Missouri has partnered with Genus plc to commercialize this method of producing virus-resistant pigs. Genus plc is currently seeking FDA approval for the use of gene editing technology for use in eradicating PRRSV.

The study also sought to determine whether editing out ANPEP would produce resistance to another alphacoronavirus, Porcine epidemic diarrhea virus (PEDV). However, pigs lacking the enzyme retained susceptibility to infection with PEDV.

The researchers note that, “Having a TGEV resistant pig may not be as valuable as a PRRSV or PEDV resistant pig, but this study still provides helpful data on coronavirus entry. Efforts can now be refocused on other mechanisms for PEDV viral entry.”

Article: Resistance to coronavirus infection in amino peptidase N-deficient pigs by Kristin M. Whitworth, Raymond R. R. Rowland, Vlad Petrovan, Maureen Sheahan, Ada G. Cino-Ozuna, Ying Fang, Richard Hesse, Alan Mileham, Melissa S. Samuel, Kevin D. Wells and Randall S. Prather, published in Transgenic Research, online 12 October 2018, doi: 10.1007/s11248-018-0100-3

[SOURCE: University of Missouri]