The flu is relentless. Crispr might be able to stop it

As he addressed At the Pandemic Research Alliance symposium in October, before an audience of virologists from China, Australia and Singapore, Wei Zhao presented an eye-catching idea.

Crispr gene editing technology is best known for providing revolutionary new therapies for rare diseases, by modifying or eliminating unwanted genes in conditions ranging from sickle cell anemia has haemophilia. But Zhao and his colleagues at the Peter Doherty Institute for Infection and Immunity in Melbourne considered a new application.

They believe Crispr could be adapted to create a next-generation treatment for influenza, whether it’s the seasonal strains that plague the northern and southern hemispheres each year, or the worrying new variants in birds and other wildlife that could spark the next pandemic.

Crispr can change the genetic code – the biological instruction manual that makes life possible – in the cells of every living thing. This means it can take different forms. The best known version is mediated by the Cas9 enzyme; this can correct errors or mutations in genes by cutting strands of DNA. But virologists like Zhao are more interested in Cas9’s less famous cousin, the Cas13 enzyme, which can do the same thing with RNA. In human cells, RNA molecules carry DNA’s instructions for making proteins, but the genetic code of flu viruses is composed entirely of RNA strands, a vulnerability that Cas13 can exploit.

“Cas13 can target these RNA viruses and inactivate them,” Zhao explained.

Human cells do not naturally produce Cas9 or Cas13; these two enzymes are found in the immune system of bacteria and microscopic organisms called archaea, where Cas13 allows them to deactivate invading viruses called phages. Zhao and a larger team of scientists are designing an innovative system to confer the same benefits on humans.

Initially pioneer in the laboratory As a new Covid antiviral, their idea is to develop a nasal spray or injection that uses lipid nanoparticles to deliver molecular instructions to flu-infected cells in the airways. It’s a two-step process. The first molecule would be an mRNA that instructs cells to make Cas13, the second being a guide RNA that directs Cas13 to a specific part of the influenza virus’s RNA code.

“Cas13 then cuts the viral RNA, disrupting the virus’s ability to replicate and effectively stopping the infection at the genetic level,” explains Sharon Lewin, an infectious disease doctor at the Peter Doherty Institute who leads the project.

Although the main goal is to use the technology as a way to fight infections in the short term, Zhao also envisions the spray being used to prevent infections, such as during a particularly virulent flu season. “Basically, you would prime the cells in your airways to produce this Cas13, as a first layer of defense,” he says. “It’s like the army: these soldiers would be armed and ready to face their enemy.”