The findings, published in Nature Communications, present a potential strategy to help mitigate the spread of avian influenza into farmed poultry from wild bird sources.
Avian influenza is widely dispersed across Asia, Europe, Africa, and the Americas representing a threat to wild bird species, economic costs to farmers, and risk to human health.
Poultry vaccination against avian influenza has not yet been reliable due to the rapid antigenic drift of field viruses and is controversial owing to political and economic implications. In chickens, avian influenza relies on a host protein (called ANP32A) for its life cycle, which represents a potential target for creating virus-resistant birds.
Mike McGrew and colleagues from Edinburgh University in the UK edited the ANP32A gene in chicken germ cells (precursors of reproductive cells) to restrict influenza A activity. They found that fully-grown chickens were resistant to a physiological dose of influenza A exposure from other infected birds, and displayed increased resilience.
However, the gene-edited chickens were not resistant against a dose 1,000 times higher. The birds showed no adverse health or egg-laying productivity effects when monitored for over two years. The authors suggest that additional editing and deletion of the other associated genes (ANP32B and ANP32E) in chicken cells would prevent virus replication.
The findings suggest gene editing as a possible route to create chickens resistant to infection by avian influenza. However, the authors caution that further study is needed to ensure animal health is not impacted and that multiple edits to the ANP32 family of genes might be required to eliminate the possibility of viral evolution.
Billions in value
Commenting on the study, Associate Professor Karinne Ludlow from the Law Faculty at Australia’s Monash University said: "Australian animal production industries are worth billions to the Australian economy and have a long history of using genetic improvement to increase productivity. Research such as [that announced today about gene editing in chickens] has enormous potential to contribute to animal welfare and food production.
“However, Australia’s preparedness for the accelerating developments in the genetic improvement of animals offered by gene editing (GE) is uncertain. Australian regulatory regimes have been reviewed in response to GE, but these focused on plants and not animals. Food safety and environmental risks raised by new genetic techniques, such as GE, are regulated in Australia but responses to other unique challenges raised by such animals have not yet been thoroughly addressed here."
Associate Professor Dimitri Perrin from the School of Computer Science, and lead of the Biomedical Data Science group from Queensland University of Technology said the study was a promising demonstration of how it could be used to control infections that already impact the farming industry and can also pose a health risk.
He added: “For any edit, it is crucial to ensure that there is no unintended modification elsewhere in the genome. Methods exist to minimise this risk and to check whether any ‘off-target’ modifications occurred. This is an important part of this study.
“It is equally important to look for unintended consequences of the desired edit. Genes are typically involved in more than one biological function. One edit could produce the desired effect on one specific function but also a detrimental effect for another one. In this study, it is encouraging that no differences in growth, external appearance, behaviour, or vaccination response were found, even though further assessments are needed.
"However, it is also true that a given biological function often involves multiple genes. A single edit is therefore not sufficient to achieve perfect results. This is true here as well. Targeting more genes increases the desired effect, but also the risk of other detrimental outcomes. More research is needed to strike the right balance."
