- The new inhalable form of DNA could help treat several lung diseases, including cystic fibrosis and respiratory distress syndrome.
- It’s made of biodegradable, positively charged polymer known as hyperbranched poly.
- Once inhaled, the nanoparticles of polymer instruct the body cells to produce a target protein from messenger RNA.
Messengers RNA — a large family of RNA that carries genetic instructions for making proteins — can be used to treat a broad range of diseases. It has several properties that make it a therapeutic, such as the ability to transfect non-dividing cells, lack of insertional mutagenesis, and controlled protein expression.
However, implementing this approach has been quite challenging so far. Scientists haven’t been able to find an efficient and reliable way to deliver molecules of messenger RNA (mRNA) to the target cells.
Recently, researchers at MIT came up with an inhalable form of mRNA that could help treat several lung-related diseases, including cystic fibrosis. They have successfully induced lung cells in mice to generate a target protein.
In particular, they used the aerosol to generate a bioluminescent protein in mice lungs. If they can do the same with therapeutic proteins, this method would revolutionize the way we treat several lung diseases today.
How Did They Do It?
For years, scientists have been working on building mRNA for treatment of cancer or genetic disorders, by essentially converting cells in the body into drug factories. But since mRNA molecules easily break down within the patient’s body, it’s necessary to transport them within a safe protective carrier.
MIT has previously developed materials for delivering mRNA and RNA interference (a process in which RNA molecules inhibit gene expression by neutralizing targeted molecules of mRNA) to the liver and other organs. Using some of these materials, researchers have developed an inhalable form of mRNA that delivers the molecules directly to the lungs.
Existing drugs for lung diseases (like asthma) are prepared in a way that they can be easily inhaled. Patients can either use a nebulizer (releases an aerosol) or an inhaler (sprays powdered particles) to inhale these drugs.
To stabilize RNA during the aerosol delivery, some previous researches focused on a material known as polyethylenimine. However, this material does not break down easily within the body, and regular dosing could cause severe side effects.
To prevent such side effects, the team used a positively charged polymer known as hyperbranched poly (siloxysilanes). Unlike polyethylenimine, these polymers are biodegradable, and thus they do not accumulate within the body.
The particles of hyperbranched poly contain spheres, about 75 nanometers in radius, with a tangled mix of mRNA molecules and polymer. Together, these particles make oxidative enzymes that produce bioluminescence protein called luciferase.
These enzymes were then suspended in droplets and delivered directly to mice via a nebulizer. Once inhaled, the nanoparticles of each droplet entered the mice cells and instructed it to produce a target protein from mRNA.
After 24 hours, lung cells started creating the bioluminescent protein, which moderately fell over time as the mRNA molecules were cleared. The team repeated the doses at certain intervals to maintain steady protein levels, which is necessary to treat long-standing lung diseases.
Epithelial cells have taken up nanoparticles (yellow) that carry mRNA encoding protein (green) | Credit: Asha Patel
Researchers found that messenger RNA was evenly scattered across the 5 lobes of the lungs. It was mostly taken up by epithelial cells that are recognized as active effectors of microbial defense. These cells are involved in many lung diseases, including respiratory distress syndrome and cystic fibrosis.
The team is now working on a method that could freeze-dry these nanoparticles so that it can be delivered via an inhaler. This would make the medication more convenient for people.