Scientists have found a way to produce a protein in mice that can block multiple variants of the SARS-CoV-2 virus from entering cells and causing respiratory disease, an advance that could lead to a “universal” treatment for COVID-19. Using messenger RNA (mRNA) packaged in lipid nanoparticles, scientists have shown in a mouse model that host cells can produce a “decoy” enzyme that binds to the spike proteins of the coronavirus, meaning the virus should not be able to capture cells in the host’s airways. and start the infection.
“Rather than messenger RNA as a vaccine, this shows that mRNA can be used as a universal therapy against various coronaviruses,” said lead researcher Gaurav Sahay of Oregon State University (OSU) in the US. “Despite mass vaccination, there is an urgent need to develop effective treatment options to end this pandemic. Several therapies have shown some efficacy, but the high mutation rate of the virus complicates the development of drugs that treat all variants of concern,” said Sahay.
Proteins are large, complex molecules that serve as the workhorses of cells and enable all biological functions in the cell. DNA contains the blueprints from which proteins are made after the code is first transcribed into mRNA. An enzyme is a type of protein that acts as a catalyst for biochemical reactions. HACE2 – short for human angiotensin-converting enzyme 2 – is an enzyme of airway cells.
It is also expressed in the heart, kidney and intestine and plays a role in many physiological functions.”Simply giving hACE2 to a COVID-19 patient would have limited effectiveness in treating the disease because the soluble form of the enzyme, the kind that can circulate in the body, has a short half-life of less than two hours, meaning it would stay in a person’s system for a very long time. Sahay said. However, lipid nanoparticles (LNPs) containing mRNA that directs enzyme production can help overcome this problem.
In a study published in ACS Nano and Advanced Science, researchers engineered synthetic mRNA to encode a soluble form of the enzyme, packaged the mRNA in lipid nanoparticles, and delivered it to cells in the liver via IV. Within two hours, the enzyme was in the mouse’s bloodstream and remained there for several days. The researchers also delivered the charged LNP by inhalation, which induced epithelial cells in the lungs to secrete soluble hACE2.
“The soluble enzyme effectively inhibited live SARS-CoV-2 from infecting host cells,” said OSU postdoctoral researcher Jeonghwan Kim. “Synthesis of mRNA is rapid, affordable and scalable, and LNP-delivered mRNA can be repeated as needed to maintain protein production until the infection resolves. Once treatment is stopped, the no longer needed soluble hACE2 clears the system within days,” said Kim.Next steps include showing that the protein prevents infection in mice, said Sahay, who added that the mRNA treatment may be “a few years” away from being available to human patients.
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