A lipid nanoparticle carrying the mRNA of a virus entering a cell
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A safer and more effective method of delivering messenger RNAs (mRNAs) to the nose and lungs could lead to improved vaccines and therapies for respiratory diseases such as Covid-19, cystic fibrosis, and asthma.
mRNAs are responsible for protein production. However, the mucus barrier in the noses, throats, and lungs prevents efficient entry of mRNAs into the cells. To overcome this, researchers led by Mark Saltzman at Yale University have developed nanoparticles that are resistant to mucus adhesion, allowing for better delivery of mRNAs.
In the case of mRNA vaccines, the desired protein is viral to help train the immune system to target the protein during a viral infection. There is also interest in using mRNAs to deliver helpful proteins for treating inherited conditions like cystic fibrosis.
Ordinary mRNAs are quickly degraded before reaching the cells, so they are usually packaged in lipid nanoparticles. However, these lipid nanoparticles are not effective at penetrating the mucus layer when inhaled or administered as a nasal spray, and large doses can cause lung inflammation.
Researchers have now optimized the delivery of mRNAs to the lungs by using nanoparticles made of a mix of two types of polymer instead of lipids. Their approach has shown success in delivering mRNAs to the cells lining the noses, throats, and lungs of mice, resulting in a significant increase in protein production compared to existing methods.
Intranasal vaccines using these polymer nanoparticles have also demonstrated impressive protection in mice vulnerable to Covid-19. The hope is that intranasal delivery will provide better protection and possibly surpass conventional intramuscular injections.
An intranasal spray alone may not be sufficient, and additional delivery devices such as nebulizers may be needed to ensure the nanoparticles reach the lungs in humans.
A company called Xanadu Bio has been established to develop vaccines for respiratory conditions based on this technology, while Saltzman’s team continues to work on treatments for cystic fibrosis.
Although treating the lungs alone may not provide a complete cure for cystic fibrosis since the disease affects other parts of the body, using polymer nanoparticles to deliver mRNAs coding for proteins that correct mutated CFTR genes could have a longer-term effect.
