Cells can be induced to produce therapeutic proteins with messenger RNA which hold great promise for treating a variety of diseases, biggest obstacle to such approaches is finding a safe and efficient way to deliver mRNA molecules to target cells.
An inhalable form of mRNA aerosol has been designed which could be administered directly to the lungs to help treat diseases such as cystic fibrosis, which was shown to induce lungs cells in mice to produce target bioluminescent proteins; if this success rate can be achieved with therapeutic proteins it may be high enough to treat many lung diseases, according to the team.
To develop an inhalable form of mRNA to allow molecules to be delivered directly to the lungs, the team set out to develop a material to stabilize RNA during the process of aerosol delivery. Biodegradable positively charged hyperbranched poly beta amino esters were investigated to avoid potential side effects of accumulation from repeated dosing. Particles consisted of spheres about 150 nanometers in diameter, combined with a mixture of the polymer and mRNA molecules that encoded bioluminescent luciferase proteins which were suspended in droplets that were delivered to mice as inhalable mist using a nebulizer.
24 hours after the mice inhaled the mRNA their lungs were found to be producing bioluminescent proteins, amounts were observed to gradually fall over time as the mRNA was cleared; and steady levels were able to be maintained with repeated doses such as may be needed if adapted to treat chronic lung disease.
After further analysis the mRNA was revealed to be evenly distributed throughout the five lobes of the lungs and to be taken up by epithelial lung cells which are implicated in cystic fibrosis, as well as other lung diseases such as respiratory distress syndrome.
The team also demonstrated the nanoparticles could be freeze dried into a powder which suggests it may be possible to deliver via an inhaler rather than a nebulizer which may be more convenient. The team plans to further investigate their findings and mRNA based therapeutics.
TranslateBio partially finding this work, and has begun Phase ½ clinical trials with an inhalable form of mRNA in patients with cystic fibrosis.
