by Prof Riaz A Shah
Genome editing in livestock has the potential to bring about significant improvements in productivity, health, and welfare, but there are still challenges that need to be addressed.
The livestock industry is facing a growing demand for animal-based foods to feed the increasing human population. This forces a need for a more sustainable approach to livestock production that considers factors such as climate change, deforestation, and conservation of biodiversity, as well as ensuring animal health and welfare. The traditional approach to increasing livestock production has been to increase the amount of land used for feeding animals, but this no longer stands feasible due to limited space for grazing land on the planet.
The twenty-first century’s cutting-edge technologies, such as gene editing, can thus be harnessed to transform the livestock industry towards efficient and safe food animal production systems.
Genome editing technology is a set of tools that precisely modifies an organism’s genetic components. There are four major types of genome editing technologies used by molecular biology scientists: Mega nucleases, Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). All these technologies work by cutting the DNA at specific places which then triggers a repair mechanism. The repair process can either rejoin the broken ends of the DNA without the use of a template or with the help of a DNA template, which allows for the introduction of new sequences within the normal genes of the organism.
Amongst these four, CRISPR-based one is the most widely used genome editing tool due to its simplicity, efficiency, and low cost. However, the application of CRISPR-Cas9 technology in livestock (sheep, goat, cattle, and buffalo) requires advanced reproductive technologies for the delivery of editing components into reproductive cells or zygotes.
For effective gene editing, currently, the most common techniques are Somatic Cell Nuclear Transfer (SCNT) and zygote microinjection, but these methods are technically challenging, labour-intensive, and costly, limiting their use to only a few specialized laboratories.
Genome editing technology has been applied in various areas of livestock production, including breeding disease-resistant animals, improving animal performance, altering milk composition, and producing hornless animals etc. Besides, CRISPR is often used for gene knockouts in medical research and therapeutic purposes. The traditional methods of livestock breeding have limitations, such as a long breeding cycle and a limited pool of genetic resources, making it difficult to improve livestock through conventional genetics. With genome editing technology, it is possible to make precise and heritable changes to the genome of diverse livestock species, leading to improved productivity, fertility, sustainability, and animal welfare.
To realise the full potential of genome editing technology in the livestock industry, it is necessary to develop strategies to translate established genome editing protocols into livestock breeding systems. The advanced reproductive technologies make it possible to apply genome editing on-farm, with minimal infrastructure and moderate cost. However, there is still a need for further research and development to ensure that the technology can be efficiently applied at scale. In conclusion, genome editing technology offers a powerful tool for improving the livestock industry, and its application has the potential to enhance productivity and profitability in livestock production.
Applications and Prospects
CRISPR is a cutting-edge gene editing technology that is rapidly gaining popularity in the livestock industry. Compared to traditional gene editings methods like ZFNs and TALENs, CRISPR is more precise and effective in modifying the genomes of livestock species. In the coming years, it is expected that CRISPR-based gene editing will be widely used in livestock breeding.
One of the primary applications of genome editing in livestock is to improve the productivity of livestock species. This can be achieved through the introduction of new traits, such as increased growth rate, improved feed conversion efficiency, and increased meat yield.
For example, researchers have used genome editing to introduce a growth hormone gene into chickens, resulting in birds that grow faster and produce more meat.
Similarly, genetic modifications have been made to pigs that improve the efficiency with which they convert feed into meat, resulting in higher meat yields per kilogram of feed. Knocking out the myostatin gene in cattle and sheep can lead to a double-muscling phenotype, resulting in superior meat production and this has been demonstrated by generating double-muscled mice who had their myostatin gene knocked out.
CRISPR can also be used to modify specific single nucleotide polymorphisms (SNPs) that impact economically important traits in livestock, such as reproductive performance. CRISPR can also be used to improve the nutritional content of milk produced by livestock. For example, knocking out the caprine beta-lactoglobulin gene in goats and introducing human lactoferrin (hlf) leads to reduced levels of beta-lactoglobulin in milk, and an increase in human lactoferrin.
CRISPR in livestock is being widely investigated for the creation of animals that are resistant to various diseases. For example, pigs that are resistant to Porcine Reproductive and Respiratory Syndrome (PRRS) can be produced by knocking out the scavenger receptor cysteine-rich receptor (CD163) gene. This leads to reduced economic costs and improved profitability of pig production, as well as reduced bio-security risks.
Cattle can also be made resistant to Mycobacterium bovis infection through genome editing, which causes significant economic losses and also poses a threat to human health. In cattle again genome editing has been used to develop cattle that are resistant to Bovine Spongiform Encephalopathy (BSE), a neurodegenerative disorder commonly referred to as mad cow disease. Likewise, CRISPR can be used to produce cattle that are resistant to Pasteurellosis, a respiratory disease caused by the bacterium Pasteurella hameolytica.
CRISPR-edited livestock are also relevant in biomedicine. For example, pigs can be edited to knock out certain genes, such as alpha-1, and 3-galactosyltransferase (GGTA1), to make them suitable for organ transplantation. Similarly, CRISPR can be used to generate livestock models for various human diseases, such as cardiovascular ailments, muscular dystrophy, and others. By knocking out the MHC system in pigs, CRISPR can also make them universal donors for organ xeno-transplantation.
Animal welfare is another important application of CRISPR in livestock breeding. Traditional methods of removing cattle horns can be painful and are not conducive to animal welfare. CRISPR-based gene editing offers a viable alternative by producing horn-free Holstein cattle.
Another application of genome editing in livestock is to improve their health, resistance to diseases and welfare. This can be achieved through the introduction of resistance genes, such as those that protect against specific viruses or bacteria, or through the elimination of genetic mutations that cause diseases. Animal welfare for example can be realized by genetic modifications to reduce the horns of cattle, reduce the need for painful dehorning procedures and reduce the risk of injury to both cattle and handlers.
Genome editing can also have a positive impact on the environment. By improving the efficiency with which livestock convert feed into meat, the demand for feed can be reduced, reducing the pressure on land used for crops and reducing greenhouse gas emissions from livestock.
Regulation and Public Acceptance: The regulation and public acceptance of genome editing in livestock is still a challenge, as there are concerns about the safety and ethics of genetic modifications. There is resistance from consumers and regulatory bodies, and the regulatory environment for genome editing is still evolving, with different countries having different approaches to the technology.
Technical Challenges: The technical challenges associated with genome editing are another limitation, as the technology is still developing and has limitations in terms of precision and efficiency. The risk of unintended off-target effects and the difficulty of controlling the expression of edited genes are also challenges that need to be addressed.
Cost: The cost of genome editing is another limitation, as the technology is still relatively new and the cost of editing genes is high. The cost of commercializing genome-edited animals and bringing them to market is also high, which limits the ability of small farmers and start-ups to participate in this field.
‘We Are Nearly Successful In Creating Gene-edited, Cloned Embryos of High Yeilding Pashmina Goats’
Ethical Considerations: The ethical considerations associated with genome editing in livestock are also a challenge. There are concerns about the potential impact of edited genes on the environment and other species, as well as the potential for the creation of genetically modified organisms that could pose a threat to biodiversity.
While regulatory agencies may consider banning the production of such animals, this may be challenging to enforce due to the widespread availability of the technology. Instead of banning, it would be more effective to establish a registry of genome-edited livestock and monitor their reproduction and consumption through oversight mechanisms. This will help to identify any potential off-target mutations that may occur with the use of genome editing technology. Additionally, investment in public education to increase awareness of the risks and benefits of genome-edited livestock is crucial to ensure the responsible use of this technology.
In conclusion, genome editing in livestock has the potential to bring about significant improvements in productivity, health, and welfare, but there are still challenges that need to be addressed. The regulation and public acceptance of the technology, the technical difficulties associated with editing genes, the cost, and the ethical considerations are all those factors that need to be considered as the field of genome editing continues to develop.
(Prominent Kashmir scientist, Prof Riyaz A Shah is the Chief Scientist at Animal Cloning and Transgenic Laboratory, Division of Animal Biotechnology, Faculty of Veterinary Sciences SKUAST-Kashmir. To his credit is the first live cloned buffalo, the first ever animal cloned ever, in India.)
Excellent sir , very interested article.