14-ATC2. Engineering resistance to disease in pigs

This project addresses food security and environmental sustainability by increasing production efficiency by reducing wastage due to disease and thus decreasing the carbon footprint of pork production. We will target the significant impact of influenza virus on one of our core livestock industries. Swine influenza (SIV) ranks consistently among the top 3 economic diseases affecting breeding, nursery, and finishing herds. In addition, influenza is the top zoonotic viral disease of swine. Our strategy is based on the recent validation of a novel RNA decoy approach in chickens. We now aim to use this newly developed technology to produce genetically engineered (GE) pigs expressing novel RNA molecules designed to prevent replication and propagation of SIV. We aim to mitigate or even eliminate mortality and morbidity due to SIV infection in pigs, while additionally protecting human health by reducing the zoonotic flu pandemic potential. It is the intention that this project will function as a 'prototype' study and, if successful, with further method refinement lead to development of a commercial product.

This project addresses food security and environmental sustainability by increasing production efficiency by reducing wastage due to disease and thus decreasing the carbon footprint of pork production. We will target the significant impact of influenza virus on one of our core livestock industries. Swine influenza (SIV) ranks consistently among the top 3 economic diseases affecting breeding, nursery, and finishing herds. In addition, influenza is the top zoonotic viral disease of swine. Our strategy is based on the recent validation of a novel RNA decoy approach in chickens. We now aim to use this newly developed technology to produce genetically engineered (GE) pigs expressing novel RNA molecules designed to prevent replication and propagation of SIV. We aim to mitigate or even eliminate mortality and morbidity due to SIV infection in pigs, while additionally protecting human health by reducing the zoonotic flu pandemic potential. It is the intention that this project will function as a 'prototype' study and, if successful, with further method refinement lead to development of a commercial product.

Who will benefit from this research?

The non-academic beneficiaries of this research include pig breeding companies, pig producers and ultimately the entire chain of users of pig products, including meat packers, processors, retailers and consumers. There are also benefits to the animal biotechnology sector.


How will they benefit from this research?

Influenza is a high profile zoonotic disease of man, livestock and wild animals. Vaccines are limited to virus strains and cannot be applied to wild animal populations. Single pandemics caused by the virus can be associated with huge numbers of human deaths in addition to vast hospital care costs. Thus, the development of novel and/or more effective strategies to control influenza are needed to limit the annual and pandemic associated human death rates, reduce burden on the health industry, while improving the sustainability of the pig industry and potentially reduce the cost of pig products.

In the pig breeding sector the research outputs will have the potential to inform future breeding programmes. The pig breeding industry has already incorporated selection for desirable disease resistance genes into breeding programmes. To date selection for disease resistance has been limited to diseases for which susceptibility is determined by a single major gene. Moreover, breeding for disease resistance is constrained by the nature of any genetic variation in susceptibility to infection. Whilst evidence for genetic variation in host responses to infection with influenza exists, the genetic control of these responses is polygenic and there is no evidence to date of major genes conferring complete resistance to influenza. With increasing capabilities to genetically modify farmed animals there are opportunities to engineer resistance. It is now timely to explore the opportunities for engineering pigs for enhanced resilience infection. The interaction between host (pig) and pathogen (influenza) are now better understood and new genome editing technologies facilitate the necessary engineering.

Public acceptance of genetically modified animals remains uncertain, especially in Europe. However, the development of non-transgenic pigs engineered for enhanced disease resistance using genome editing technology, which introduces no exogenous DNA, has the potential to re-shape the debate. Moreover, given the impact of influenza in farm animals and man, beneficial impacts could be delivered to the pig industry within 3-5 years of project completion.