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Messenger RNA (mRNA), a type of RNA, can trigger cells to produce proteins that can, in turn, be used for the treatment of certain diseases. mRNA is typically created during transcription and can carry genetic information from DNA, in the form of “code words” to other parts of the cell for processing.

In the past, scientists have struggled to find a reliable and efficient method to transfer these therapeutic mRNA molecules to cells…until now.



Typical mRNA activity in a eukaryotic cell. (Source: Public Domain)

Typical mRNA activity in a eukaryotic cell. (Source: Public Domain)

Lung diseases such as pneumonia, constructive obstructive pulmonary disease (COPD), cystic fibrosis (CF), etc. affect millions of people each year, and many individuals remain undiagnosed even with modern diagnostic tests. In fact, the American Lung Association has rated COPD as the third leading cause of death in the United States.

Now, a team of engineers at the Massachusetts Institute of Technology (MIT) has found a unique way to deliver mRNA to patients of lung disease. They designed a non-invasive, inhalable aerosol that can directly administer IVT (in vitro transcribed)-mRNA to the lungs; IVT-mRNA is known to have multiple therapeutic applications.

The full paper, lead-authored by Asha Kumari Patel, a former postdoc at MIT, has been published in a recent issue of the journal, Advanced Materials.

Breathe In (the mRNA)

The aerosol was created by a nanoformulation of biodegradable polymers called hyperbranched poly (beta-amino esters) (hPBAEs) that were synthesized to form safe and stable polyplexes.

Previously, PEI or polyethylenimine was considered for use in the delivery of inhalable DNA to the lungs, but owing to the material’s side effects and the fact that it doesn’t break down easily, hPBAEs were used instead, for this study.

This polymer mixture and mRNA molecules, designed to be spherical and about 150 nm in diameter, encoded for a bioluminescent protein, luciferase. These particles were suspended in droplets and sprayed as a mist, via a nebulizer, that ultimately ended up in the lungs (taken up by epithelium cells) of model mice. It was seen that about 101.2 ng-1 of the luciferase protein was produced, 24 hours after administration.

Image shows that the lung epithelial cells have incorporated the mRNA-carrying-nanoparticles (yellow). The fluorescent green represents the mRNA which has encoded for the luciferase protein. (Source: Asha Patel)

Image shows that the lung epithelial cells have incorporated the mRNA-carrying-nanoparticles (yellow). The fluorescent green represents the mRNA which has encoded for the luciferase protein. (Source: Asha Patel)

Like Patel explained, “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.”

On continuously administering hpBAE-mRNA, there was a consistent yield of the protein in the lungs of the animal, and no form of toxicity was observed either. In addition, the delivery was localized to the lungs and not to surrounding tissues or organs, as no luminescence was noticed elsewhere. As the mRNA dissipated, the amount of protein reduced too.

Future Cure for Lung Diseases?

From the results, it was inferred that the delivery of IVT-mRNA by inhalation could be a viable system of transportation to the lungs, and it could prove clinically significant as well.

The researchers of the study indicated that if the same success rate could be achieved in humans with therapeutic proteins, certain chronic lung diseases could become better treatable.

Furthermore, the use of an inhaler, instead of a nebulizer, was demonstrated as part of the research. The MIT-team freeze-dried and converted the nanoparticles into a powder that could easily be delivered to the lungs too, and it could also be more convenient for patients.

This study was partially funded by a company called TranslateBio (other funders United Kingdom Engineering and Physical Sciences Research Council and the Koch Institute Support (core) Grant from the National Cancer Institute) that develops mRNA therapeutics. Apparently, they have begun clinical trials on this inhalable mRNA and are currently in the process of testing it on patients with cystic fibrosis.

Lead author of the paper, Patel, also plans to investigate mRNA-based therapeutics further, in her laboratory based at Imperial College, London.

Top Image: A single strand of RNA. (Source: nobeastsofierce/Shutterstock)


  1. messenger RNA/mRNA, Scitable by Nature Education,, (accessed Jan 9, 2019)
  2. How Serious Is COPD, American Lung Association,, (accessed Jan 9, 2019)
  3. Engineers create an inhalable form of messenger RNA, 2019, MIT News,, (accessed Jan 9, 2019)
  4. Patel, A. K. et al. (2019), ‘Inhaled Nanoformulated mRNA Polyplexes for Protein Production in Lung Epithelium,’ Advanced Materials
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Meghna Rao, MSc

A postgraduate in Bioscience with work experience in research and communications in the fields of science, health and medicine. Her specializations include writing and developing scientific material for websites, blogs, and other print and digital media, content curation and management, and medical proofreading and editing. She also has a fair knowledge in marketing communications and science journalism. Also, Meghna is passionate about yoga, working with non-profits and travel blogging. Read More

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