Classical swine fever virus (CSFV) is a highly infectious and deadly disease among pigs, with outbreaks leading to huge livestock losses. Now, researchers from Jilin University in China have genetically modified pigs to be resistant to the virus, which will also pass that resistance down to their offspring.
CSFV is highly contagious, and pigs infected with the virus usually die within a few weeks. Extensive vaccination procedures have seen the disease effectively eradicated in North America, Australia, and much of Europe, but CSFV remains common throughout the rest of the world. That means outbreaks occasionally still occur even in areas with high vaccination rates, and in those cases control methods are unfortunately limited to culls.
A more efficient technique could be to genetically engineer animals that are resistant to the virus. To do so, the Jilin researchers combined the CRISPR-Cas9 gene-editing tool with a technique known as RNA interference (RNAi). CRISPR allows scientists to make cut-and-paste edits to the genome of an organism, and in this case the team used the system to insert small hairpin RNAs (shRNAs) that have antiviral effects.
This technique was performed on pig fetuses, leading to animals with an innate resistance to CSFV. To test it out, the researchers split the pigs into two rooms, each containing three transgenic (gene-edited) pigs, three un-edited control pigs, and one unedited pig infected with the virus. All of the natural pigs became fatally infected with the disease. Although the transgenic pigs were also infected, their symptoms were far less severe and non-fatal, and they had much lower virus numbers in their bloodstream.
The team also confirmed that these disease-resistant traits were passed down to at least the first generation of the edited pigs’ offspring. They also tested for off-target genetic mutations and found none – although they do admit that their search was limited only to the parts of the genome where these mistakes would be most likely to crop up. Mutations might appear in unexpected locations instead, which will require further study to uncover.
If all goes well, the team says the technique could eventually be used as a way to permanently introduce disease-resistance traits into large populations of pigs. The technique may also apply to other species of livestock.
This isn’t the first time pigs have been successfully genetically engineered. Last year researchers used CRISPR to create pigs free of harmful retroviruses, making them safer donors for organ transplants into humans. Another team engineered piglets with less body fat, making them better suited to cold weather – with a bonus side order of low-fat bacon.
The new research was published in the journal PLOS Pathogens.