EXPERT REACTION: Gene-editing could protect chickens against bird flu

The research is quite promising, but editing the ANP32A gene was not enough, as the virus was able to invade host cells using alternative ANP32 protein family members, chicken ANP32B and ANP32E.

If chickens could be engineered to be resistant to avian influenza viruses, that may reduce the risk of the emergence of a human pandemic virus from avian influenza. However, avian influenza spreads globally not just through poultry trading, but also through wild waterfowl such as ducks and geese.

These birds can spread avian influenza as they migrate across flyways between countries and continents, independent of farmed poultry. During the unprecedented global spread of H5N1 clade Clade 2.3.4.4b in the last few years, other wild bird species have also become infected, such as Godwits, Plovers and Curlews. So, engineering farmed chickens alone is not enough.

The other main concern is influenza A viruses are highly mutable and subject to continual antigenic drift. This means the virus itself will likely evolve to overcome engineered traits in the birds.

One of the greatest potential uses of this technology is for influenza vaccine manufacturing. Many vaccines are manufactured using embryonated hens' eggs. A problem with highly pathogenic avian influenza viruses is that they are also pathogenic to eggs, so this requires higher doses of antigen when making vaccines, and the process of vaccine manufacturing can be slowed down as a result.

During a newly emerged pandemic, having engineered eggs that are resistant to highly pathogenic avian influenza can be of great benefit for vaccine manufacturing. Having said that, new vaccine technologies for influenza vaccines are becoming more common now, and reliance on eggs for vaccine manufacturing may not be as common in a few years.

By allowing targeted modifications in virtually any species of interest, genome editing unlocks new research directions. This article is 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.
 
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.

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.