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Gene editing pigs for disease resistance

Genetic resistance to the PRRS virus by gene editing is a game-changer for the pork industry.

Porcine Reproductive and Respiratory Syndrome (PRRS) virus was first detected in the U.S. in 1987. Pigs that contract the disease have extreme difficulty reproducing, don’t gain weight and have a high mortality rate. To date, no vaccine has been effective, and the disease costs North American farmers more than $660 million annually.

Now, a team of researchers from the University of Missouri, Kansas State University, and Genus plc have bred pigs that are not harmed by the disease.

“Once inside the pigs, PRRS needs some help to spread; it gets that help from a protein called CD163,” said Randall Prather, distinguished professor of animal sciences in the College of Agriculture, Food and Natural Resources. “We were able to breed a litter of pigs that do not produce this protein, and as a result, the virus doesn’t spread. When we exposed the pigs to PRRS, they did not get sick and continued to gain weight normally.”

Uncoat the virus

For years, scientists have been trying to determine how the virus infected pigs and how to stop it. Previously, researchers believed that the virus entered pigs by being inhaled into the lungs, where it attached to a protein known as sialoadhesin on the surface of white blood cells in the lungs.

However, two years ago Prather’s group showed that elimination of sialoadhesin had no effect on susceptibility to PRRS. A second protein, called CD163, was thought to “uncoat” the virus and allow it to infect the pigs. In their current study, Prather’s team worked to stop the pigs from producing CD163.

“We edited the gene that makes the CD163 protein so the pigs could no longer produce it,” said Kristin Whitworth, co-author on the study and a research scientist in MU’s Division of Animal Sciences. “We then infected these pigs and control pigs; the pigs without CD163 never got sick. This discovery could have enormous implications for pig producers and the food industry throughout the world.”

No other changes to the pigs

While the pigs that didn’t produce CD163 didn’t get sick, scientists also observed no other changes in their development compared to pigs that produce the protein.

The early-stage results of this research are promising. The University of Missouri has signed an exclusive global licensing deal for potential future commercialization of virus resistant pigs with the Genus, plc. If the development stage is successful, the commercial partner will seek any necessary approvals and registration from governments before a wider market release.

Game changer

“The demonstration of genetic resistance to the PRRS virus by gene editing is a potential game changer for the pork industry,” said Jonathan Lightner, Chief Scientific Officer and Head of R&D of Genus plc. “There are several critical challenges ahead as we develop and commercialize this technology; however, the promise is clear, and Genus is committed to developing its potential. Genus is dedicated to the responsible exploration of new innovations that benefit the well-being of animals, farmers, and ultimately consumers.”

“At the end of our study, we had been able to make pigs that are resistant to an incurable, untreatable disease,” said Kevin Wells, co-author of the study and assistant professor of animal sciences at MU. “This discovery could save the swine industry hundreds of millions of dollars every year. It also could have an impact on how we address other substantial diseases in other species.”

In addition to Whitworth and Wells, Prather’s research team included collaborators at Genus plc, and Kansas State University. The study, “Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus,” is being published in Nature Biotechnologythis month.

Genus plc, the U.S. Department of Agriculture (USDA) and University of Missouri’s Food for the 21st Century Program provided funds for the research.

25 years fighting PRRS

PRRSv is the most significant and harmful pig disease faced by many farmers, causing animal reproductive failure, reduced growth and premature death. Even though it has challenged the pork industry for more than 25 years, there is currently no cure for PRRSv. The technology has the potential to eliminate the disease impact on the animals, improve the well-being of pigs, and enhance pig farm productivity, which ultimately will help meet the global demand for pork products.

Using precise gene editing, the University of Missouri was able to breed pigs that do not produce a specific protein necessary for the virus to spread in the animals. The early stage studies conducted by the University demonstrate these PRRSv resistant pigs, when exposed to the virus, do not get sick and continue to gain weight normally.

Five years until resistant pigs available

Genus will continue to develop this technology, and the company expects it will be at least five years until PRRS resistant animals are available to farmers. Genus intends to commercialize the technology through PIC, its porcine division.

The university research results have been published in the peer-reviewed scientific journal, Nature Biotechnology, on December 7.

About Genus plc and the Pig Improvement Company (PIC)

Headquartered in Basingstoke, United Kingdom, Genus is a world-leading pioneer in animal genetics. PIC is a subsidiary of Genus, and has been selling swine breeding stock for over 50 years.

Genus companies operate in over 25 countries on six continents, with research laboratories located in Madison, Wisconsin, USA. For more information visit www.genusplc.com.

About Porcine Reproductive and Respiratory Syndrome Virus

PRRSv is a devastating disease that can cause persistent infection in pigs and lead to reproductive failure, reduced growth and premature death. There is currently no cure for the disease, which causes the suffering or death of millions of pigs and piglets each year. Current treatment is expensive with limited effectiveness.

PRRSv is considered to be the most economically burdensome viral disease of pig farms in Asia, Europe and North America. Financial losses are mainly due to increased death loss, poor reproductive performance and increased use of vaccines and medications.

Secondary diseases following a PRRSv outbreak on a farm can further reduce productivity and lead to additional costs. Diagnostic testing and herd monitoring after a PRRSv introduction are necessary to develop comprehensive control strategies, which are costly and have limited effectiveness.

In 2006, a more severe form of PRRSv decimated pig populations throughout China. According to the China Animal Disease Control Center, in the summer of 2006, a new severe variant of PRRSv affected over two million pigs.

A 2011 Iowa State Universityi study estimated PRRSv cost the U.S. pork industry $664 million per year, and in Europe figures are estimatedii at €1.5 billion per year.

About gene editing technology

Gene editing allows precise changes to be made in the genome of the animal without introducing genetic material from another organism. In the case of the PRRSv resistant pigs, small changes were made to inactivate a single gene from the pigs that produces a protein, known as CD163, the PRRS virus requires for infection to occur.

The gene editing technology used to create protection from PRRSv does not involve transplanting genes from one species to another.

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