Inhaled CRISPR RNA-Editing Tool Effective at Stopping Influenza and SARS-CoV-2 Replication

Inhaled CRISPR RNA-Editing Tool Effective at Stopping Influenza and SARS-CoV-2 Replication

Researchers at the Georgia Institute of Technology and Emory University have utilized CRISPR technology for a potential new treatment for RNA-based viruses such as SARS-CoV-2 and influenza, which stops the viruses from replicating. Not only does the treatment kill the viruses, it could also be administered by patients at home using a nebulizer to deliver the gene editing tool directly to the lungs.

CRISPR uses guide RNA to identify a specific section of the DNA, and a Cas protein to perform a double stranded cut. To target RNA-based viruses, the researchers used mRNA technology to encode a Cas13a protein, which destroys the part of the viral RNA that is used to replicate.

The beauty of the system is the ease at which it can be changed to target different viruses. All that is required is to provide a different guide RNA, which is just one sequence of RNA which can be rapidly developed once the genetic sequence of a virus is known.

“One of the first things that society and the CDC are going to get when a pandemic emerges is the genetic sequence. It’s one of the first tools that the CDC and the surveillance teams are going to use to identify what kind of virus this is and to begin tracking it,” said Daryll Vanover, PhD, co-author of the study. “Once the CDC publishes those sequences—that’s all we need. We can immediately screen across the regions that we’re interested in to target it and knock down the virus.”

The researchers developed their system to target an influenza virus, then changed the guide RNA and used it to target SARS-CoV-2. The system was tested on mice and hamsters and was shown to be effective with no side effects.

The researchers say this treatment would have been effective against 99% of the flu strains that have been in circulation in the past century. The section of the influenza RNA targeted – polymerase genes – are used by the virus to replicate and are generally conserved in new strains. The researchers also targeted sections of RNA in SARS-CoV-2 that have so far been conserved in all of the new variants that have emerged in recent months, so the treatment should be effective at treating most new variants soon after they emerge. Should a variant emerge with a major change that renders the treatment ineffective, a new guide RNA could be developed rapidly once the genetic sequence of the virus is known.

There are 219 species of viruses that are known to infect humans, and 214 of those viruses are RNA-based and could potentially be targeted using this technology.

While there is concern about the use of CRISPR in humans, the protein used to perform the cut does not enter the cell nucleus and does not cut DNA. Cas13a was chosen because it is an inherently safe technique that could be used in humans. There is, however, a lot of work still to do before the treatment could be considered for use in humans. The researchers are now taking a closer look at the safety of the system with a view to moving to human trials.

You can read more about the study in the paper – Treatment of influenza and SARS-CoV-2 infections via mRNA-encoded Cas13a in rodents – which was recently published in Nature Biotechnology. DOI: 10.1038/s41587-021-00822-w