Award details

Validation of genome edited disease resistant pigs

Reference	BB/M028313/1
Principal Investigator / Supervisor	Professor Christopher Whitelaw
Co-Investigators / Co-Supervisors
Institution	University of Edinburgh
Department	The Roslin Institute
Funding type	Research
Value (£)	121,660
Status	Completed
Type	Research Grant
Start date	01/07/2015
End date	30/06/2018
Duration	36 months

Abstract

Infectious disease is the biggest threat to animal protein food security in the 21st century. As production intensifies the livestock industry becomes more vulnerable to devastating disease outbreaks potentially affecting millions of animals. In this project, we target porcine viral diseases for which no effective vaccination or other mitigating strategy is available. Our previous research has identified genetic variation in RELA as potentially underlying the dramatic difference in host response to ASFV that is seen in pigs. RELA encodes the p65 component of the NFkB immune regulatory transcription factor. Using state-of-the-art genome editing technology we are producing various RELA alleles which we hypothesise could improve the resistance/resilience of such pigs to ASFV. Given the role of NFkB we further hypothesise that these RELA alleles may alter how pigs respond to other viruses, e.g. SIV and PRRSV. All three viruses were selected given the impact they pose to the pig breeding and the zoonotic nature of SIV. Genome edited RELA pigs will be breed to produce test cohorts of animals that comprise non-edited, heterozygous for a given test alleles and homozygous for this allele. These cohorts will be genotyped prior to challenge with the viruses. This project will enable us to validate if any of these novel alleles confer improved viral resistance/resilience through disease challenge experiments.

Summary

Impact Summary

Who will benefit from this research? The potential 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 potential benefits to the animal biotechnology sector. How will they benefit from this research? ASFV, PRRSV and influenza are a high profile disease of pigs. In addition influenza is perhaps the most important zoonotic disease of our time. Vaccines are either not available or limited to virus strains and cannot be applied to wild animal populations. Thus, the development of novel and/or more effective strategies to control these viruses are needed and will improve 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. 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 (ASFV, PRRSV, influenza) are now better understood and new genome editing technologies facilitate the necessary engineering. In the long term this work aims to contribute to the science-based evidence relating to the use of genetically engineered animals in the food chain. As such it will contribute to the debate and practices surrounding our food chain. 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, beneficial impacts could be delivered to the pig industry within 3-5 years of project completion.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Animal Health, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	Innovate UK (TSB) [2011-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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