



Homer J. Simpson once referred—unknowingly of course—to the pig as a “magical, mystical creature,” and for many, culinarily speaking, this is right on the mark. Yet, public health officials and farmers view the “enchanted” porcine much differently. In addition to the animals being a haven for zoonotic diseases that often spread to humans, viral infections in pigs cost the swine industry billions of dollars in lost product every year. Creating animals that are genetically resistant to various viruses would not only save money, but could also provide a greater means to protect the population from potentially epidemic diseases such as influenza.

Now, a team of investigators from the University of Edinburgh and the biotech company Genus have used the genome-editing tool CRISPR/Cas9 to engineer pigs that are potentially resistant to porcine reproductive and respiratory syndrome (PRRS), which causes severe breathing problems in young pigs and breeding failures in pregnant females.

The findings from this study were published recently in PLOS Pathogens in an article entitled “Precision Engineering for PRRSV Resistance in Pigs: Macrophages from Genome Edited Pigs Lacking CD163 SRCR5 Domain Are Fully Resistant to Both PRRSV Genotypes While Maintaining Biological Function.”

“Genome editing offers opportunities to boost food security by reducing waste and losses from infectious diseases, as well as improving animal welfare by reducing the burden of disease,” explained senior study investigator Alan Archibald, Ph.D., head of the division of genetics and genomics at the Roslin Institute within the University of Edinburgh. “Our results take us closer to realizing these benefits and specifically address the most important infectious disease problem for the pig industry worldwide.”





Initial findings from the study revealed that cells from the engineered pigs are completely resistant to infection with both major subtypes of the virus that causes the disease. Moreover, the investigators say that the animals are otherwise healthy and the gene edit should not affect their ability to fight off other infections.

Previous studies have shown that the PRRS virus targets macrophages—specifically a molecule on the surface of these cells called CD163, which plays a key role in enabling the PRRS virus to establish an infection. The investigators used the CRISPR/Cas9 technique to cut out a small section of the CD163 gene in the pigs' DNA code. Tests using the edited cells from the pigs with the modified CD163 gene have confirmed that the genomic edit blocks the virus from being able to cause infection.

The research team is looking ahead toward the next stage in the study, in which they will test whether the pigs are resistant to infection when exposed to the virus. Previous work by a different research group produced pigs that lacked the entire CD163 molecule and did not become ill when exposed to the PRRS virus. However, in this latest study, only the section of CD163 that interacts with the PRRS virus was removed, allowing the molecule to retain its other biological functions.

PRRS is endemic in most pig-producing countries worldwide. Vaccines have mostly failed to stop the spread of the virus, which continues to evolve rapidly. Consequently, it is one of the greatest challenges facing pig producers today.

“This result furthers the case for the criticality of CD163 in PRRS virus infection and demonstrates that a targeted removal of the viral interacting domain can confer resistance while the remainder of the protein is present,” concluded Jonathan Lightner, Ph.D., CSO for Genus. “This, and other gene edits, will be evaluated as Genus advances the development of gene editing to confer PRRS virus resistance. Genus is committed to pioneering the responsible application of technology to animal genetic improvement to enhance the well-being of animals, the livelihoods of farmers, and the sustainable approach to producing food for a growing global population.”























