Key Points:
- Researchers used messenger RNA packaged in lipid nanoparticles to prevent coronavirus infection in mice.
- The work focuses on HACE2, an enzyme of the airway cells.
- The mRNA treatment in the study could be administered via IV or inhalation.
Researchers at Oregon State University have produced a proof of principle for a new “universal” means of treating COVID-19. In a mouse model, the team showed it’s possible to prompt the production of a protein that can block multiple variants of the SARS-CoV-2 virus from entering cells and causing illness.
Using messenger RNA packaged in lipid nanoparticles, the scientists showed in a mouse model that host cells can produce a “decoy” enzyme that binds to coronavirus spike proteins, meaning the virus shouldn’t be able to latch onto cells in the host’s airway and start the infection process.
“Rather than messenger RNA as a vaccine, this shows that mRNA can be used as a universal therapy against different coronaviruses,” said study author Gaurav Sahay, associated professor of pharmacology. “Despite mass vaccination, there is an urgent need to develop effective treatment options to end this pandemic. Several therapies have shown some effectiveness, but the virus’ high mutation rate complicates the development of drugs that treat all variants of concern.”
The study focused on HACE2, an enzyme of the airway cells. But, simply giving a COVID-19 patient hACE2 would have limited effectiveness since its soluble form has a short half-life—less than two hours.
So, in the study, published in Advanced Science, the researchers engineered synthetic mRNA to encode a soluble form of the enzyme, packaged the mRNA into lipid nanoparticles (LNP) and delivered it to cells in the liver with an IV. Within two hours, the enzyme was present in the mice’s bloodstream—and it stayed there for days.
The scientists also delivered the loaded LNP via inhalation, prompting epithelial cells in the lungs to secrete soluble hACE2.
“The soluble enzyme effectively inhibited live SARS-CoV-2 from infecting host cells,” said study author and OSU postdoctoral researcher Jeonghwan Kim. “The synthesis of mRNA is fast, affordable and scalable, and LNP-delivered mRNA can be repeated as necessary to sustain protein production until the infection subsides. Once treatment stops, the no-longer-needed soluble hACE2 clears the system in a matter of days.”
Information courtesy of Oregon State University.