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CRISPR-Based mRNA Treatment Delivered to Lungs via Nebulizer Stops Replication of SARS-CoV-2 Virus

By HospiMedica International staff writers
Posted on 08 Mar 2021
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Image: CRISPR-Based mRNA Treatment Delivered to Lungs via Nebulizer Stops Replication of SARS-CoV-2 Virus (Photo courtesy of Daryll Vanover)
Image: CRISPR-Based mRNA Treatment Delivered to Lungs via Nebulizer Stops Replication of SARS-CoV-2 Virus (Photo courtesy of Daryll Vanover)
An easy-to-deliver mRNA treatment uses a type of CRISPR to target viral RNA and appears to stop replication of both the flu and SARS-CoV-2 viruses in the lungs.

The new treatment developed by researchers at the Georgia Institute of Technology (Georgia Tech; Atlanta, GA, USA) and Emory University (Atlanta, GA, USA) appears to stop replication of both flu viruses and the virus that causes COVID-19. Best of all, the treatment could be delivered to the lungs via a nebulizer, making it easy for patients to administer themselves at home.

The therapy is based on a type of CRISPR, which normally allows researchers to target and edit specific portions of the genetic code, to target RNA molecules. In this case, the team used mRNA technology to code for a protein called Cas13a that destroys parts of the RNA genetic code that viruses use to replicate in cells in the lungs. The team tested its approach against flu in mice and SARS-CoV-2 in hamsters. In both cases, the sick animals recovered. This is the first study to show mRNA can be used to express the Cas13a protein and get it to work directly in lung tissue rather than in cells in a dish. This is also the first study to demonstrate the Cas13a protein is effective at stopping replication of SARS-CoV-2.

What’s more, the team’s approach has the potential to work against 99% of flu strains that have circulated over the last century. It also appears it would be effective against the new highly contagious variants of the coronavirus that have begun to circulate. The key to that broad effectiveness is the sequence of genes the researchers target. For their study, the researchers looked at the genetic sequences of prevalent flu strains over the last 100 years and found regions of RNA that are unchanged across nearly all of them. Likewise, in SARS-CoV-2, the sequences the researchers targeted so far remain unchanged in the new variants. The approach means the treatment is flexible and adaptable as new viruses emerge, according to the researchers.

The team’s approach also was sped along by their previous work on delivering mRNA to mucosal surfaces like those in the lungs. They knew there was a good chance they could tackle respiratory infections with that approach. They decided to use mRNA to code for the Cas13a protein because it’s an inherently safe technique. The researchers believe that additional work remains - especially understanding more about the specific mechanisms that make the treatment effective. It has produced no side effects in the animal models, but they want to take a deeper look at safety as they consider moving closer to a therapy for human patients. The researchers believe that result in lead candidates for clinical trials could be available in a matter of weeks - which is about how long it took them to scan the sequences, design their guide strands, and be ready for testing in this study.

“It’s really quite plug-and-play,” said Philip Santangelo from the Wallace H. Coulter Department of Biomedical Engineering. “If you're talking about small tweaks versus large tweaks, it's a big bonus in terms of time. And in pandemics - if we had had a vaccine in a month or two after the pandemic hit, think about what things would look like now. If we had a therapy a month after it hit, what would things look like now? It could make a huge difference, the impact on the economy, the impact on people.”

Related Links:
Georgia Institute of Technology
Emory University


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