Improving resistance to infectious salmon anaemia using genome editing: Novel approaches to tackling viral disease in aquaculture

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Salmon aquaculture is worth approximately £1 billion per annum to the UK economy and is the primary source of employment in many rural and coastal communities. Infectious disease epidemics constrain sustainability and expansion, and cause major negative economic and animal welfare impact. Infectious Salmon Anaemia Virus (ISAV) is a notifiable disease that requires culling of stocks for control. Improving genetic resistance of salmon stocks is a critical component of tackling ISAV. Genome editing raises the possibility of creating targeted and informed de novo disease resistance alleles (e.g. CD163 deletions for PRRS virus in pigs), and to test the causality of naturally-occurring variants, and potentially increase genetic gain in breeding programs. ISAV is a close relative of influenza, and knowledge of the conserved function of viral binding, internalisation and replication across orthomyxoviridae is one route to identifying target genes for editing.

This proposal will use forward and reverse genetics to identify genome editing targets for resistance to ISAV in Atlantic salmon. Harnessing large scale disease challenge and pedigree data provided by the industrial partner Benchmark, the team will map and characterise genes underpinning host resistance. Genome editing will be applied in cell culture to screen putative functional resistance candidate genes, with targets including 'naturally-occurring' variants, and de novo targets with a predicted key role in the ISAV host-cell interaction. These approaches will deliver high priority candidates for in vivo genome editing of salmon embryos, followed by an ISAV challenge to assess the resistance of the edited fish. The outcomes will include fundamental knowledge of mechanisms of genetic resistance to ISAV, and potential novel strategies to combat viral diseases impacting on salmon aquaculture. As such, it is aligned to the BBSRC priorities on 'Sustainably enhancing agricultural production' and 'Animal health'.

This proposal is applying novel and innovative methods with potential to develop an Atlantic salmon with resistance to ISAV as a result of genome editing. This outcome, and the research that leads to it, is likely to have high impact for academic, industry, government and societal groups.

It is likely that the major impact of the proposal will be medium and long term, due to uncertainty over the regulatory landscape and public appetite for genome editing technologies. However, high profile success stories are key, and this proposal has high potential to deliver such success stories. Use of genome editing to produce a disease resistant food fish has animal welfare, environmental and economic benefits.

It should also be noted that intermediate impacts of the research will include improved methods of genomic selection for disease resistance in aquaculture breeding, improved knowledge of host-pathogen interaction for ISAV, and optimised methods of using CRISPR-Cas9 for animal bioscience research. The following groups can expect positive impact from the proposal:

(i) UK and global aquaculture industry: ISAV has a major negative impact on aquaculture production, and is a notifiable disease in the UK. This proposal has potential for developing disease-resistant strains of salmon within a relatively short timeframe, and major breeding companies such as Benchmark view genome editing as a high priority R&D activity. While the regulatory landscape for genome editing is uncertain at present, achievement of the aims of this proposal is likely to be a driver to incorporate this technology to benefit food production.

(ii) Animal breeding industry: The improved genomic selection arising from the identification of functional genomic variants will have short term impact on selective breeding programmes. In the longer term, aquaculture species such as salmon are amenable to genome editing due to their high fecundity and easily visible embryos, and may be a good model for other species.

(iii) UK economy: This project has potential for long term impact for the UK economy via improved sustainable production of a high quality food product with reduced environmental impact. There will be direct contribution to the UK treasury via improved market share for the project partner Benchmark, and downstream impacts on fish farming companies, and the communities that depend on these industries.

(iv) Academic community: The impact for academic groups will include improved knowledge of the genetic basis of resistance to ISAV in salmon, specific genes and mutations impacting resistance, and improvement in methods of effective genome editing of cell lines and embryos.

(v) UK science capacity. This project will enable capacity and expertise for application of genome editing technology to address (applied) biological questions via research programs in academia and industry. This should lead to the UK taking a leading global position in the application of this technology for animal research and production.

(vi) Political and regulatory bodies. The regulatory landscape of genome editing currently precludes its use for food production in the short term. Successful achievement of the objectives of this project will influence ethical and regulatory frameworks to encourage full exploitation of genome editing in an informed and responsible manner.

(vii) General public and society. This project has potential to influence societal attitudes to genome editing in aquaculture and, more broadly, in food production animals. In the longer term, there will be direct benefits to society via improved economic stability and reduced environmental impact of the aquaculture industry.