A new study brought the possibility of gene-edited chicken breasts appearing on your grocery shelves one step closer to reality. Scientists edited the genomes of chickens to make them more resistant to bird flu — a technique that could protect poultry from the disease, which threatens both birds and humans.
The study, published Tuesday in the journal Nature Communications, details a first-of-its-kind attempt to prevent bird flu in chickens. A lot more research will be needed before you might pick up a gene-edited chicken wing to nibble on, however.
“This is a proof of concept that we can move towards making chickens resistant to the virus, but we’re not there yet,” said Wendy Barclay, a virologist at Imperial College London and study co-author in a press conference. “We’d need more robust edits to really shut down the virus replication.”
Editing Out Bird Flu
While the coronavirus rampaged through the world, another virus also blazed across the globe: H5N1, a highly infectious strain of bird flu. The virus has killed hundreds of millions of farm birds and wild birds on every continent except Antarctica since 202. Aside from the clear threat to birds, scientists also worry that the rampant spread of H5N1 stokes the risk of the virus jumping to humans.
Right now, poultry farmers have few tools to slow the spread of the virus beyond quarantining and culling sick birds. And vaccinating chickens against avian influenza is tough, both because the virus evolves rapidly and because it costs a lot of money and resources.
“Gene editing promises a new way to make permanent changes in the disease resistance of an animal,” said Mike McGrew, a biologist at The Roslin Institute and Royal School of Veterinary Studies who co-authored the research. Those changes “can be passed down through all the gene-edited animals to the offspring to protect the poultry and reduce risks to farmers and wild birds,” he said.
One particular gene, called ANP32, stood out to McGrew and colleagues as a promising target to edit resistance into the chicken genome. The gene encodes a protein that all influenza viruses (not just bird flu) need to replicate within a host’s cells.
“It occurred to us that if you could disrupt that interaction in some way, perhaps by gene editing, then the virus would not be able to replicate,” said Barclay. “This strategy could be used not just for H5N1 bird flu, but for any of the strains because it’s fundamental to how the virus works.”
The researchers used the CRISPR/Cas9 gene editing system to introduce small but consequential changes to the ANP32 in chicken germline cells. Those edited germline cells were injected into chicken embryos and eventually became the sperm and egg cells of adult chickens. The researchers then mated those chickens together to produce chickens with the resistance gene.
The team closely monitored the growth and health of the edited chickens for over two years, finding them to be just as healthy as non-edited chickens. Then, they inoculated the chickens with a low dose of avian influenza, akin to what they might encounter in natural settings. Under those conditions, the chickens were almost entirely resistant to infection — just one of ten birds got infected.
About half of the gene-edited birds couldn’t withstand a dose about 1,000 times higher, the researchers found, though the birds still shed lower levels of virus than their non-edited counterparts and didn’t go on to infect 10 other gene-edited chickens that were later housed with the infected birds.
Not ready for prime time
Avian influenza can evolve very rapidly, and the researchers found evidence that the virus changed in some worrying ways in gene-edited chickens that experienced breakthrough infections.
“We did detect mutations in exactly the part of the virus which the ANP32 protein interacts with,” said virologist Barclay. Since the chickens didn’t have the protein the virus normally uses to hijack cells, the virus adapted to use related but sub-optimal proteins, including one found in humans.
“We didn’t see that that led to the virus growing any better in human airway cells,” said Barclay, who also stressed that there are many other hurdles the virus would have to clear to jump from birds to humans. “But the fact that we’re taking a step in the direction of making the virus more able to infect, perhaps, other species is not something that we want to be doing at all.”
Preventing that kind of unwanted evolution requires chickens that are 100% resistant to infection. To that end, the researchers tried to block the evolution they saw in gene-edited chickens by additionally tweaking two ANP32-related genes in chicken cells in the lab. That worked, and the thrice-edited cells proved wholly resistant to infection in the lab, but the researchers suspect introducing that many changes might also harm a chicken’s health in ways that aren’t immediately obvious, underlining how much work remains before gene-edited chickens could be rolled out to grocery stores.
“We can’t even think about going forward with this process until we have the perfect edits that would make the animal completely resistant to avian influenza,” said McGrew.
