Genetically modified chickens show promise in the fight against avian flu

Scientists have successfully used gene editing techniques to limit the spread of avian flu in chickens.

In a UK first, researchers have sought to limit, but not completely, the transmission of avian flu virus in birds by precisely changing a small part of their DNA.

The genetically modified birds showed no signs that the change had an impact on the  health or welfare of the animals.

But  researchers say that while the results are encouraging, more gene editing is needed to create chickens that cannot be infected with bird flu.

The study, conducted by researchers from the University of Edinburgh, Imperial College London and the Pirbright Institute, is published in the journal Nature Communications.  Professor Wendy Barclay, Head of  Infectious Diseases at Imperial College London, said: “This work is an exciting collaboration, combining our expertise in virology with the advanced genetics capabilities of the Roslin Institute.

“While we haven't yet got the perfect combination of genetic modifications to use this method in practice, the results have taught us a lot about how influenza viruses behave inside  infected cells. infection and how to slow down its multiplication process”.

Avian flu poses a major threat globally, with  devastating impacts on domestic and wild bird populations. In the UK alone, the current H5N1 avian flu outbreak  has decimated seabird populations and cost the poultry industry more than £100 million.

In the latest study, researchers aimed to test whether precise changes to the chicken genome have the potential to create virus-resistant birds.

The team bred chickens with small changes in a gene called ANP32A. During  infection, influenza viruses hijack the ANP32A protein to facilitate their replication. But when the genetically modified birds were exposed to a normal dose of virus (the H9N2  avian flu strain), 9 out of 10 birds remained uninfected and there was no spread to other chickens.

When  birds were exposed to  artificially high doses of the virus, only half of them became infected. The single gene edit also provided some protection against transmission, with  much lower  virus loads in infected gene-edited birds than in unaltered birds.

Additionally, the modification also helps limit the spread of the virus to just one in four unmodified chickens placed in the same incubator. There was no transmission to genetically modified birds.

The analysis showed that in the edited birds, the virus had adapted to seek help from two related proteins for replication – ANP32B and ANP32E.

After laboratory tests, the researchers discovered that certain mutations could allow the virus to use the human version of ANP32, but that replication remained low in cell cultures from the human respiratory tract. The researchers point out that additional genetic modifications are necessary for the virus to be able to infect and spread effectively in humans.

According to the research team, the results demonstrate that a single genetic modification is not strong enough to create disease-resistant chickens. To prevent the emergence of viruses that were able to adapt to a single mutation, the team then used  triple mutations to target additional proteins (ANP32A, ANP32B and ANP32E) in the cell. Chickens are raised in a laboratory. In laboratory cell cultures, virus growth was successfully prevented in the cells by changes in  all three genes. In the future, researchers hope to develop chickens with these three edits, but no birds have been created at this time.

The researchers said the study highlights the importance of responsible gene editing and the need to be alert to the risks of  viral evolution in undesirable directions if the ability is not achieved. completely drug resistant, experts said.

Professor Mike McGrew, from the Roslin Institute at the University of Edinburgh and lead researcher on the study, said: “Avian flu poses a major threat to bird populations. Vaccinating against the virus poses a number of challenges, with significant financial and practical  issues involved in rolling out the vaccines. “Gene editing offers a promising route to long-term disease resistance that can be passed from generation to generation, protecting poultry and minimizing risks to humans and wild birds. Our work shows that stopping the spread of avian flu in chickens will require several simultaneous genetic changes.

The research was funded by the UKRI Biotechnology and Biological Sciences Research Council.