Inhalable mRNAs will boost vaccines and therapies for lung conditions

Delivering mRNAs to the cells lining the nose and lungs will make vaccines more effective and may also lead to better treatments for conditions such as cystic fibrosis

By Michael Le Page

16 August 2023

A lipid nanoparticle carrying the mRNA of a virus entering a cell

Dr_Microbe/iStockphoto/Getty Images

A safer and more effective way of delivering mRNAs to the nose and lungs could lead to vaccines that provide better protection against respiratory infections such as covid-19, as well as superior treatments for lung conditions such as cystic fibrosis and asthma.

mRNAs, or messenger RNAs, are the templates for making proteins. By packaging them into small particles that don’t stick to mucus, Mark Saltzman at Yale University and his colleagues have increased the efficiency with which mRNAs can enter the cells lining the noses, throats and lungs of mice. “The mucus is a barrier,” says Saltzman. “The trick is to make the nanoparticles resistant to adhesion to the mucus.”

If mRNAs are added to cells, those cells can be made to produce any desired protein. The effect is only temporary, however, because mRNAs break down after days or weeks.

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With mRNA vaccines, the desired protein is viral, as this trains the immune system to recognise and target that protein during a viral infection. There is also a lot of interest in using mRNAs to deliver beneficial proteins for treating inherited conditions. For instance, cystic fibrosis is caused by a build-up of mucus in the lungs due to mutations in a protein called CFTR. Efforts to treat it by getting mRNAs for working versions of CFTR into the lungs have shown promise.

However, naked mRNAs are destroyed before they can get into cells, so they are usually packaged in fatty particles. These lipid nanoparticles work well when injected, as done with the mRNA covid-19 vaccines, but they aren’t very good at getting through the mucus layer that protects the lungs when inhaled or administered as a nasal spray.

What’s more, larger doses of mRNAs are needed for treating conditions like cystic fibrosis than are used in vaccination, as the mRNAs need to get into a higher proportion of cells. Breathing in such large doses of lipid nanoparticles can cause lung inflammation.