After three decades of research, Helen Sang, a geneticist at the University of Edinburgh’s Roslin Institute, reached her first success in gene editing by creating chickens that demonstrate a resistance to the avian flu.
Sang and her colleagues wrote in their findings that in chickens, the influenza A virus (IAV) relies on host protein ANP32A. In their study they a particular approach to genome editing known as CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats) to generate “homozygous gene edited chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction.”
The team put the avian influenza virus into the nostrils of 20 two-week-old chicks, half of which were subject to the modified gene. After the IAV challenge, the researchers wrote, at least nine out of 10 chicks (nearly the entire half) “remain uninfected.”
However, this system will not be put to the test anytime soon, as the gene-edited chickens still became sick when they were exposed to larger amounts of the flu virus, even though the infections did develop more slowly, reaching lower viral levels,
“What this showed is a proof of concept,” says Wendy Barclay, a virologist at Imperial College London who worked on the new study. “But we’re not there yet.”
In addition, the researchers say that if a mutated virus does arise to confront the gene-edited chickens, it would have a “high probability” of better infecting mammals - including humans.
“A water-tight system where no more replication takes place in chickens is necessary,” Sander Herfst, a virologist from Erasmus University Medical Center, said. To accomplish their goal, the scientists will have to continue to use the genome editing approach (CRISPR-Cas9) in their tests.
Additionally, per Barclay, test tube experiments showed that even high levels of the influenza virus could not infect chicken cells if that virus lacked all three ANP32 genes.
However, the researchers will have to find a way to keep the chickens healthy too, as removing all three genes could have a negative effect on the chicken’s health. The goal then, would be to find a way to alter the ANP32 gene so that it could ward off the virus, but still be able to function as a protein.
Still, the discovery is one step further in scientists’ efforts to prevent virus outbreaks.
“This strategy could be used not just for H5N1 (bird flu virus) but for any of the strains because it’s fundamental to the way the virus works,” said Barclay.
Richard Webby, a bird flu expert at St. Jude Children’s Research Hospital, said the scientific community would "absolutely" reach the point where researchers will be able to “manipulate the host genome to make them less susceptible to flu. That’ll be a win for public health.”
The findings were published Tuesday in the journal Nature Communications.