New research demonstrates that gene editing can prevent infection of classical swine fever (CSF), a highly contagious, often fatal disease in swine. CSF, also known as hog cholera, is endemic in many countries and classified as a foreign animal disease in the U.S. which means it is not normally found in the U.S. and has the potential for rapid spread if it were to come to the U.S.
This research, led by a team at the Roslin Institute, used gene-editing technology to alter a protein which the virus depends on to make copies of itself in the pigs’ cells.
The results showed gene-edited pigs exposed to CSF remained unaffected, while unedited animals showed clear signs of disease.
“This genetic change offered complete protection from infection without any observable negative effects on the animals’ health or development, and researchers believe the gene-edited pigs would be very unlikely to spread the virus to other animals,” the Roslin Institute said in a release.
The researchers say gene editing could contribute to an integrated strategy for disease prevention, in combination with vaccines and measures to prevent disease spread in farmed animals.
A Targeted Approach
Before producing gene-edited pigs, researchers worked with collaborators to study how aspestiviruses, a group of viruses that includes CSF, interact with pig cells.
A key pig protein, DNAJC14, has previously been shown to play an important role in the virus replication process when studied in cultured cells. The team focused on this protein in lab studies. By altering the gene that produces DNAJC14, they were able to prevent the virus from reproducing.
The Roslin Institute said making the same genetic change in live animals could produce livestock resistant to these viruses.
Researchers took the study a step further and “made a precise change in a region of the DNAJC14 gene in pig embryos, preventing the virus from using the pig cells to produce all of its own viral proteins.”
After this, the embryos were implanted into surrogate mothers, and once the pigs reached “adulthood,” researchers exposed these gene-edited pigs to CSF virus.
“Experts monitored the pigs’ health over several weeks, finding no signs of viral infection in the edited animals,” the article said. “By contrast, pigs which had not undergone gene-editing, and were exposed the virus, showed typical signs of infection.”
Cross-species potential
The pestivirus family includes diseases such as bovine viral diarrhea virus in cattle and border disease virus in sheep.
“Our research highlights the growing potential of gene editing in livestock to improve animal health and support sustainable agriculture,” says Simon Lillico, core scientist at the Roslin Institute. “While previous research had identified this protein’s role in cell cultures, translating that into living animals is a major step, and one that requires the infrastructure to breed, monitor and safely test gene-edited livestock. Our Large Animal Research and Imaging Facility allows us to gene edit and assess a variety of livestock species, with colleagues at the Animal and Plant Health Agency providing expertise and biosecure facilities for this viral challenge.”
Although there are CSF vaccines, researchers say control remains challenging due to virus persistence and transmission between species.
“The same genetic edit could theoretically be applied to other livestock species, offering broader protection against disease,” the research team explains
Editor’s Note: This research was published in Trends in Biotechnology, in collaboration with animal genetics company Genus, and colleagues at the Animal and Plant Health Agency (APHA) and the University of Lubeck, Germany. The work was supported by a BBSRC National Bioscience Research Infrastructure grant and facilitated by the Large Animal Research and Imaging Facility at the University of Edinburgh. The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies.
