Researchers at Edinburgh’s Roslin Institute have developed pigs that are resistant to Classical swine fever (CSF), using gene-editing technology.
The Roslin team used the technology to alter a protein which the virus depends on to make copies of itself in the pigs’ cells.
Gene-edited pigs exposed to CSF, a highly contagious, often fatal disease that is endemic in many countries, 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, according to the researchers, who believe the gene-edited pigs would be very unlikely to spread the virus to other animals.
The research team said gene editing could contribute to an integrated strategy for disease prevention, in combination with vaccines and measures to prevent disease spread in farmed animals.
Before producing the gene-edited pigs, researchers worked with collaborators to study how a group of viruses including CSF, collectively known as pestiviruses, interact with pig cells.
They focused on a key pig protein, named DNAJC14, that had previously been shown to play an important role in the virus replication process when studied in cultured cells. In lab studies using these cells, altering the gene that produces DNAJC14 prevented the virus from reproducing.
This suggested that making the same genetic change in live animals could produce livestock resistant to these viruses.
Live trial
Researchers 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.
The embryos were then implanted into surrogate mothers, and once the pigs reached adulthood, the research team exposed these gene-edited pigs to classical swine fever virus.
Experts monitored the pigs’ health over several weeks, finding no signs of viral infection in the edited animals. By contrast, pigs which had not undergone gene-editing, and were exposed the virus, showed typical signs of infection.
CSF, last seen in the UK in 2000, continues to cause significant outbreaks in parts of Asia, Africa, Latin America and Europe, resulting in trade bans and serious financial losses for farmers. While there are vaccines for the disease, control remains challenging due to virus persistence and transmission between species.
The pestivirus family includes diseases such as bovine viral diarrhoea virus in cattle and border disease virus in sheep. The same genetic edit could theoretically be applied to other livestock species, offering broader protection against disease, the research team explained.
Gene editing potential
“Our research highlights the growing potential of gene editing in livestock to improve animal health and support sustainable agriculture,” said Dr 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.”
This research was published in Trends in Biotechnology, in collaboration with animal genetics company Genus, 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.