JAN 06, 2019 12:38 PM PST

An Inhalable Form of Messenger RNA Might be a New Kind of Therapeutic

WRITTEN BY: Carmen Leitch

Messenger RNA (mRNA) is an important intermediary molecule that normally carries genetic information from the genome to the ribosome, where it is translated into protein (illustrated in the video). Researchers are trying to use mRNA to stimulate cells to produce therapeutics, but one major challenge is getting the mRNA into the right place. Now scientists at MIT have created a form of mRNA that can be inhaled. For people with lung diseases like cystic fibrosis, this technology may help create new treatments.

"We think the ability to deliver mRNA via inhalation could allow us to treat a range of different disease of the lung," said the senior author of the work Daniel Anderson, an associate professor in MIT's Department of Chemical Engineering, and a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

The researchers were able to successfully induce lung cells of mice to generate a specific protein, which glowed. Now they can try to produce therapeutic proteins in the same way, turning a patient’s cells into miniature drug factories.

The body can easily break mRNA down, so to use it as a therapeutic, it must be protected. Anderson's lab has already worked in this area to deliver mRNA to other parts of the body. In this work, they wanted to generate mRNA that could be inhaled for delivery to the lungs, a method that’s already used for drug delivery, like asthma inhalers. They needed to stabilize the mRNA for its transmission to the lungs. They turned to a biologically safe and biodegradable material, hyperbranched poly (beta-amino esters), a type of positively charged polymer.

The team created spheres that were a mixture of the mRNA and the polymer, about 150 nanometers in diameter. They used an mRNA that codes for a bioluminescent protein called luciferase. The spheres were suspended in droplets and given to the mice using a nebulizer, creating an inhalable mist.

"Breathing is used as a simple but effective delivery route to the lungs. Once the aerosol droplets are inhaled, the nanoparticles contained within each droplet enter the cells and instruct it to make a particular protein from mRNA," said lead study author Asha Patel, former MIT postdoc and current assistant professor at Imperial College London.

Within 24 hours of inhalation, lung cells in the mice generated the glowing protein, which gradually decreased over time as the cells degraded the mRNA. Repeated dosing steadily maintained the protein. After assessing the lungs, the researchers saw that the mRNA had been distributed evenly, and was primarily taken up by epithelial cells, which are impacted in cystic fibrosis and other lung diseases. 

Anderson discusses RNA delivery in the talk above.

 

Sources: AAAS/Eurekalert! via MIT, Advanced Materials

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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