The flu is relentless. Crispr may be able to turn it off

As he addressed Before an audience of virologists from China, Australia and Singapore at the Alliance for Epidemic Research Symposium in October, Wei Zhao presented an eye-catching idea.

Crispr gene editing technology is known for providing groundbreaking new treatments for rare diseases, or modifying or eliminating rogue genes in conditions ranging from Sickle cell disease to Hemophilia. But Zhao and his colleagues at the Peter Doherty Institute for Infection and Immunity in Melbourne envisioned a new application.

They believe CRISPR could be designed to create a next-generation treatment for influenza, whether it’s the seasonal strains that infect the northern and southern hemispheres on an annual basis, or new variants of concern in birds and other wildlife that could lead to the next pandemic.

Crispr can modify the genetic code — the biological instruction book that makes life possible — within the cells of every organism. This means they can take different forms. The most well-known version is mediated by the Cas9 enzyme. This can repair errors or mutations within genes by cutting strands of DNA. But virologists like Zhao are more interested in a lesser-known Cas9 enzyme, Cas13, which can do the same thing with RNA. In human cells, RNA molecules carry instructions from DNA to make proteins, but the genetic code of influenza viruses consists entirely of RNA strands, a weakness that Cas13 can exploit.

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

Human cells do not naturally make Cas9 or Cas13; Both of these enzymes are found in Immune systems Bacteria and microscopic organisms called archaea, where Cas13 enables them to inactivate invading viruses called phages. Zhao and a wider team of scientists are creating an innovative system to give the same benefits to humans.

Starting Laboratory leader As a new Covid antiviral, their idea is to develop a nasal spray or injection that uses lipid nanoparticles to deliver molecular instructions to influenza-infected cells in the respiratory tract. It is a two-stage process. The first molecule will be an mRNA that directs cells to make Cas13, while the second molecule will be a so-called 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,” says Sharon Lewin, an infectious disease physician at the Peter Doherty Institute, who is leading the project.

While the main goal will be to use the technology as a means of reducing short-term infections, Zhao also envisions using the spray to prevent infection, for example during a particularly deadly flu season. “It’s basically going to prime the cells in the respiratory system to produce this Cas13, as a first layer of defense,” he says. “It’s like an army, where these soldiers are armed and ready to face their enemy.”