February 23, 2017

expert reaction to study looking at gene-edited pigs and resistance to Porcine Reproductive and Respiratory Syndrome

Scientists publishing in PLOS Pathogens report that genome edited pigs show signs of resistance to Porcine Reproductive and Respiratory Syndrome (PRRSV) – a panzootic infectious disease of pigs, causing economic losses to the world-wide pig industry.

Prof. Robin Lovell-Badge, Group Leader, The Francis Crick Institute, said:

“This is a well thought out, carefully done study with very promising results. Indeed, it would appear to be an excellent example of how to use genome editing to build disease resistance into animals. It reveals the current pitfalls in terms of efficiencies and mosaicism in the founder animals, but perhaps these will soon disappear with the rapid progress in improving the methods.

“With respect to succeeding with the aims of making animals resistant to PRRSV, the proof will depend on studies of virus infection in the pigs rather than in cells in vitro – but, hoping that this is not a rasher statement than I would usually make, it all looks good.”

Prof. Ian Jones, Professor of Virology at the University of Reading has provided the following response:

“This is an interesting approach to the control of Porcine Reproductive and Respiratory Syndrome (PRRSV), an important virus affecting the pig industry for which there is no current vaccine.

“The authors have removed part of the virus receptor, the cellular doorway the virus uses to initiate infection. If the virus can’t get in then disease is prevented.

“The drawbacks of this approach are that all commercial stock would have to be bred to include this mutation, which takes time and public acceptance, and there is always the worry that the PRRSV virus would mutate to use a different receptor and so gain access by a ‘backdoor’. The proposed challenge studies should help address whether this is likely or not.”

Prof. Douglas Kell, Professor of Bioanalytical Science, University of Manchester, said:

“While we cannot easily control human and animal pathogens and the extent of their virulence, there is an increasing recognition that subsets of the host populations can exhibit resistance, and this can allow the relevant genes to be identified. In the case of livestock, this permits the engineering of the host to produce resistance.

“The UK is the world leader in the pig breeding industry, and an important target of modern livestock breeding necessarily involves breeding resistance to their pathogens.

“This is a superb piece of work, in which the receptor for the Porcine Reproductive and Respiratory Syndrome Virus (a very nasty virus of pigs) was determined, and its properties modified using modern gene editing methods to stop the virus entering the target cells. The expected result was that this would make the resultant pigs resistant to said virus, as proved to be the case. This has very substantial welfare, social and economic benefits for pigs and their farmers.

“One may hope that similar strategies can now be applied to other kinds of livestock and their pathogens.”

* ‘Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function’ by Christine Burkard et al. published in PLOS Pathogens on Thursday 23 February 2017. 

Declared interests

Prof. Robin Lovell-Badge: “I have no conflict of interests.”

Prof. Ian Jones: Ian’s received funding from the MRC, DEFRA, Wellcome Trust, WHO, BMGF – but no expressed conflicts.

Prof. Douglas Kell: “For 5 years from 2008-2013, I was CEO of BBSRC, that – as stated – provides strategic funding to the Roslin.”