Inhalable RNA could breathe new life into lung cancer treatments
Lung epithelial cells that have taken up the mRNA particles (yellow dots), which makes them glow green(Credit: Asha Patel)
In the body, messenger RNA (mRNA) molecules are in charge of instructing cells to produce specific proteins, and hijacking this natural system is emerging as a promising new way to treat a wide variety of illnesses. Now, researchers at MIT have developed an inhalable mRNA aerosol that can take the molecules directly to the lungs, as a potential new treatment for cystic fibrosis or lung cancer.
Proteins are often called the workhorses of the cell, performing a huge range of functions like transporting molecules or aiding with chemical reactions. Using mRNA to control which proteins are produced could be an important new type of treatment for many ailments. In recent years researchers have used mRNA in universal flu vaccines and alongside CRISPR, "reprogramming" liver DNA to reduce cholesterol.
In the new study, the MIT team set out to develop a way to deliver mRNA molecules to the lungs, where they could coax lung cells to produce proteins that can help fight diseases like cystic fibrosis or lung cancer. Obviously, the most direct way to get medication to the lungs is by making it inhalable.
For their tests, the MIT researchers used mRNA molecules that encode for luciferase, a bioluminescent protein. It doesn't have any medicinal benefit, but was chosen so that the team could easily see if the treatment had reached the lungs and was getting the message to the cells there.
These molecules were mixed with a kind of polymer known as hyperbranched poly (beta amino esters), which helps protect the drug payload from being broken down in the body too quickly. The 150-nm-wide particles were suspended in liquid droplets and then administered to mice as a breathable mist through a nebulizer.
Sure enough, 24 hours after the treatment the team observed that the lung cells were producing luciferase. The levels of the protein gradually dropped, which is to be expected as the body clears away the mRNA, but the team could keep luciferase levels high by repeating the treatment. This might be a necessary step to help treat chronic illnesses.
When the researchers looked a little closer, they noticed that the mRNA had made it into all five lobes of the lungs. Epithelial lung cells, which line the surface of the organ, had taken up the most mRNA. Since these cells are involved in cystic fibrosis and respiratory distress syndrome, inhalable mRNA could be particularly well-suited to treating these diseases.
The team says the particles could also take the form of a freeze-dried, inhalable powder, which would make them as easy for patients to carry and self-administer as an asthma inhaler. A clinical trial of an mRNA-based treatment for sufferers of cystic fibrosis is already underway.
The research was published in the journal Advanced Materials.