Genetically Engineered Pigs to Fight Disease

Porcine Reproductive and Respiratory Syndrome (PRRS) causes significant harm to the welfare of pigs worldwide, as well as annual revenue losses of £1.8 billion in the US and Europe. Research into the PRRS virus has been of great importance in recent years but vaccination and other measures have failed to fully control the disease. The University of Edinburgh’s Roslin Institute have produced PRRS-resistant pigs by genetic engineering and bred them successfully across several generations. In a new development, the researchers have signed a license agreement with a leading animal genetics company to conduct further studies. They hope to gain FDA approval, which could lead to disease-resistant pigs for meat production with significant potential benefits for animal welfare and the porcine industry.

In this blog, we discuss PRRS-resistant pigs and how this could help alleviate the economic burden of porcine disease. 

The Burden of PRRS

PRRS is a viral disease which creates two different pathologies depending on the age of the infected pig. The reproductive pathology causes fetal abortion and stillborn litters, while the respiratory pathology causes breathing problems and affects pigs of any age. The PRRS virus modulates the host immune system with some similarities to HIV; the cause of death is rarely the virus itself but more often the result of a secondary bacterial infection (Butler et al. 2014). The death rate can be alarmingly high, with 80% of piglets who are infected with PRRS shortly after birth dying as a result of infection.

PRRS was first described in North Carolina, Iowa, and Minnesota in the late 1980s. The disease spread rapidly to become a pandemic; by 1992, PRRS was identified in Canada and several European countries. The burden of this disease is so significant that whole production systems have been designed around mitigating its impact. Although these control strategies include biosecurity, depopulation, and vaccination, no single strategy has been able to control PRRS and vaccines are only partially effective. For this reason, PRRS remains the most economically important disease affecting porcine animal health. 

A History of Porcine Gene Editing

Humans have long used selective breeding to enhance desirable traits of domestic pigs. The recent ease and availability of genetic engineering has made direct genome manipulation possible, accelerating this process immensely. In 2020, the first genetically-modified pigs were approved by the FDA for human therapeutic use and consumption. These GalSafe pigs are engineered to eliminate the alpha-gal protein on the surface of pig cells, which can cause allergic reactions in people with Alpha-Gal Syndrome (AGS). Importantly, these pigs could provide a source of human medical products, such as heparin, suitable for those with AGS. 

This approval was the first of its kind, but there are efforts worldwide to create modified pigs for a whole range of purposes, including for faster growth and thermoregulation, and of course resistance to viral diseases, with a goal of regulatory approval (Yang and Wu. 2018). 

PRRS Gene Editing

Efforts to create PRRS resistance have focused on the scavenger receptor cysteine-rich domain 5 (SRCR5) region of the CD163 receptor, which the PRRS virus uses to infect cells (Yang et al. 2018). This was the approach taken by the team at the Roslin Institute in Edinburgh, who modified the genome to delete exon 7 of the CD163 gene using CRISPR/Cas9 gene editing. This modification led to expression of CD163 without SRCR5, meaning the virus could not infect cells while leaving the remaining biological functions of CD163 intact. Accordingly, modified pigs challenged with a highly virulent strain of PRRS showed no signs of infection, and lung and lymph node analysis showed no virus replication, in comparison to unmodified pigs. The modified pigs were fully resistant to infection by the PRRS virus and also appeared healthy across the three generations tested, with no breeding abnormalities identified (Burkard et al. 2018).

Next Steps

With the success of the PRRS-resistant pigs, the researchers at the Roslin Institute teamed up with an animal genetics company. The collaborators signed a licensing agreement which will allow them to test generations of pigs and conduct the studies required for FDA approval.

If FDA approval is successfully granted, the introduction of PRRS-resistant pigs could have significant benefits for animal welfare and also productivity of the pork industry. In their 2018 publication, authors from the Roslin Institute note that the animals could decrease the requirement for antimicrobial products in pig production (Burkard et al. 2018). With the ever-present threat of antimicrobial resistance, this would be a major benefit (Lekagul et al. 2019).