Gene editing applications in livestock

Background

The term “gene editing” or “genome-editing” encompasses several biotechnologies that allow the precise manipulation of an animal’s genome, with CRISPR/Cas9 systems being the most frequently used. Most approaches intervene at the early embryonic stages or in cell cultures that are subsequently used in somatic cell nuclear transfer or cloning. In 2019, Australia’s Gene Technology Act 2000 was amended to exclude organisms modified using the genome-editing applications known as SDN-1 (site-directed nuclease) from the scope of genetically modified organisms (GMO) regulation.

Using genome-editing, scientists can introduce beneficial genetic variation that confers desirable traits into the germline of selected parents, making the genetic improvement inherited by the next generation (see below for some examples of its application). CSIRO is an “accredited organisation” certified by the Office of the Gene Technology Regulator, under section 92 of the Gene Technology Act 2000, with the required containment facilities at our Chiswick Research Station, Armidale, NSW.

Global application

Countries with regulations that classify commercialisation of gene-edited animals without transgenes as non-GMO include Argentina, Brazil, Japan, Australia (indels only by process), Nigeria, Ethiopia, Colombia, Paraguay, India and Kenya (Ledesma and Van Eenennaam 2024, Liu et al., 2022; Mueller & Van Eenennaam, 2022). The legal landscape continues to change in many jurisdictions, meaning regular evaluation is likely to be informative.

Select examples of gene editing in production animals

Targeting the reduction of painful husbandry practices

• The introduction of a polled allele into otherwise horn cattle to avoid de-horning. The first proof-of-principle animal was generated nearly ten years ago (Carlson et al., 2016). The concept was to increase the frequency of polled animals in a population without sacrificing previous selection improvements.
• Gene editing to block sexual maturation in pigs. The concept involves introducing a relatively simple edit that aims to remove castration from the production system (Florez et al., 2023).

Enhancing animal resilience to the environment – improving tolerance to heat stress

• The introduction of the slick coat allele. The slick coat trait is a well-known characteristic of Senepol cattle. This genetic variant is associated with improved thermo-tolerance in tropical environments. The allele found in Senepol has been introduced via gene editing in Angus and Holstein cattle, with animals being considered non-GMO in Brazil and Argentina.
• Editing the coat colour for improved heat tolerance. The concept was to create a line of Holstein cattle with a genetic modification resulting in diluted colour (grey and white instead of black) (Laible et al., 2021). These animals are on the ground, and trait measurements have started.

Gene editing towards decreasing susceptibility to diseases

• The development of PRRSV-resistant pigs. This is by far the most successful example of gene editing to control diseases in animal production with a global impact (Burkard et al., 2017, 2018; Salgado et al., 2024).
• The development of BVDV-resistance cattle. In 2023, a scientific article described the development of a calf resistance to bovine viral diarrhoea virus (BVDV). This certainly represents a great advance, but a lot of follow-up studies will be necessary to characterise and validate the trait to ensure it is reproducible and effective. 

Our current interests in gene editing applied to animal agriculture are:

1.       Contribute to the discussion about gene editing applications in livestock and the regulatory processes.
We believe that a broader conversation around gene editing in livestock is needed in Australia.

2.       Development of gene editing-based technologies for improved control of livestock reproduction.
We recognise that better control of an animal’s reproduction will significantly impact the industry; new advanced biotechnologies can play an important role, potentially creating new production systems that optimise resource utilization and welfare of animals.

References

Burkard et al., (2017) 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. 10.1371/journal.ppat.1006206.

Burkard et al., (2018) Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection. 92:10.1128/jvi.00415-18.

Carlson et al., (2016) Production of hornless dairy cattle from genome-edited cell lines. 10.1038/nbt.3560.

Flórez et al., (2023) CRISPR/Cas9-editing of KISS1 to generate pigs with hypogonadotropic hypogonadism as a castration free trait. 10.3389/fgene.2022.1078991.

Laible, et al. (2021) Holstein Friesian dairy cattle edited for diluted coat colour as a potential adaptation to climate change. 10.1186/s12864-021-08175-z.

Ledesma and Van Eenennaam (2024) Global status of gene edited animals for agricultural applications. 10.1016/j.tvjl.2024.106142.

Liu, et al., (2022). Enhancing Animal Disease Resistance, Production Efficiency, and Welfare through Precise Genome Editing. 10.3390/ijms23137331.

Mueller & Van Eenennaam (2022). Synergistic power of genomic selection, assisted reproductive technologies, and gene editing to drive genetic improvement of cattle. 10.1186/s43170-022-00080-z.

Office of the Gene Technology Regulator (2024). Accredited organisations. https://www.ogtr.gov.au/what-weve-approved/accredited-organisations

Salgado, et al., (2024) Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection. 10.1016/j.antiviral.2024.105793. Workman, et al. (2023) First gene-edited calf with reduced susceptibility to a major viral pathogen. 10.1093/pnasnexus/pgad125.

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