Pigs that can resist a fatal virus
Genome editing to make pigs resistant to deadly virus.
Porcine Reproductive and Respiratory Syndrome (PRRS) is a viral disease that cause breathing and reproductive disease in pigs. The main victims are new-born piglets who often don’t survive. Infections with the virus cost the pig industry more than £1.75 billion per year in the US and Europe alone. The disease occurs in most pig producing countries globally, including the UK. This makes PRRS an economic and welfare threat to the local and global pig industry.
Here at The Roslin Institute, scientists have found a way to make pigs resistant to the virus using genome editing. Removing a small section of the gene that makes the pigs susceptible to the virus means that they don’t get sick.
This discovery could have the potential to increase pig health and the profitability of pig farming around the world.
We’re very excited about these results. The pigs we produced were fully resistant to the PRRS virus and this has the potential to reduce losses in the farming industry while improving animal welfare.
How do farmers manage PRRS today?
At the moment, farmers try to prevent the disease on their farms with high levels of biosecurity and, in some cases, through vaccination. But despite these measures the number of PRRS virus infected pigs in the UK has risen significantly over the past 20 years.
Vaccines are used in around 45% of farms in England. The nature of PRRS itself makes it hard to develop a good vaccine as it changes quickly. Mainly live-attenuated vaccines are used for vaccination but they have been shown to revert to virulence and cause disease in many cases.
How does PRRS virus cause disease?
Viruses enter cells in the body and hijack the cell machinery. In this process cells often get severely damaged, which causes the immune system to react and symptoms of an illness to appear.
In PRRS, the virus attacks a specific group of immune cells called macrophages, which are found all over the body and in the bloodstream. These cells have a protein on their surface called CD163 that PRRS virus binds to and uses to invade the cell (macrophages).
CD163 is an important immune system protein and plays multiple roles to help the body stay healthy. Because the CD163 protein is important for the immune system, removing it to prevent viral infection is likely to have negative effects.
Information from other researchers revealed that the virus only binds to a specific area of CD163. If we could target this area alone, we could remove the binding target of the virus, without compromising the pig’s immune system.
How did we target PRRS?
We use a technique called genome editing which allows us to change the DNA sequence of an organism. This is done by adding removing or changing letters in the DNA alphabet.
Dr. Tait-Burkard and her team removed the binding target of PRRSV from the CD163 gene on the macrophages. Genome editing was done by using the CRISPR/Cas9 system that allowed us to remove only a small section of the gene. This prevented the virus from entering the cell. The receptor was kept similar enough to its original form to allow the pig’s immune system to work normally and maintained its function in the bloodstream.
The technique was first used in lab-grown pig cells before being used to create genome edited pigs. Initial experiments in cells derived from the pigs and later in the pigs themselves showed that they were completely resistant to infection. Pigs with the edited version of CD163 were shown to be otherwise normal and healthy.
What is next for PRRS resistant pigs?
We are excited to have produced pigs that are resistant to PRRS - this is a promising area of research. Within this project we collaborated with one of the world’s leading pig breeders, Genus PIC. They are now busy re-making PRRSV-resistant gene edited animals in their elite stock and are continuing a collaborative engagement with the US Food and Drug Administration (FDA), regarding the regulatory framework for these pigs in the USA. They also recently announced a collaboration with a Chinese company. In Europe, genome edited animals are currently banned from the food chain, so PRRS-resistant pigs can't be farmed. Wide ranging conversation that include farmers, policy makers and consumers is needed before genome editing research can reach its full potential.
How we use gene editing (YouTube)
The CRISPR-Cas 9 Gene Editor (YouTube)