Self-Motivation
David Goggins
Former Navy Seal
Career Development
Bryan Cranston
Actor
Critical Thinking
Liv Boeree
International Poker Champion
Emotional Intelligence
Amaryllis Fox
Former CIA Clandestine Operative
Management
Chris Hadfield
Retired Canadian Astronaut & Author
Learn
from the world's big
thinkers
Start Learning

Engineers create an inhalable form of messenger RNA

Patients with lung disease could find relief by breathing in messenger RNA molecules.

Getty Images


Anne Trafton | MIT News Office

Messenger RNA, which can induce cells to produce therapeutic proteins, holds great promise for treating a variety of diseases. The biggest obstacle to this approach so far has been finding safe and efficient ways to deliver mRNA molecules to the target cells.

In an advance that could lead to new treatments for lung disease, MIT researchers have now designed an inhalable form of mRNA. This aerosol could be administered directly to the lungs to help treat diseases such as cystic fibrosis, the researchers say.

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

The researchers showed that they could induce lung cells in mice to produce a target protein — in this case, a bioluminescent protein. If the same success rate can be achieved with therapeutic proteins, that could be high enough to treat many lung diseases, the researchers say.

Asha Patel, a former MIT postdoc who is now an assistant professor at Imperial College London, is the lead author of the paper, which appears in the Jan. 4 issue of the journal Advanced Materials. Other authors of the paper include James Kaczmarek and Kevin Kauffman, both recent MIT PhD recipients; Suman Bose, a research scientist at the Koch Institute; Faryal Mir, a former MIT technical assistant; Michael Heartlein, the chief technical officer at Translate Bio; Frank DeRosa, senior vice president of research and development at Translate Bio; and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute.

Treatment by inhalation

Messenger RNA encodes genetic instructions that stimulate cells to produce specific proteins. Many researchers have been working on developing mRNA to treat genetic disorders or cancer, by essentially turning the patients' own cells into drug factories.

Because mRNA can be easily broken down in the body, it needs to transported within some kind of protective carrier. Anderson's lab has previously designed materials that can deliver mRNA and another type of RNA therapy called RNA interference (RNAi) to the liver and other organs, and some of these are being further developed for possible testing in patients.

In this study, the researchers wanted to create an inhalable form of mRNA, which would allow the molecules to be delivered directly to the lungs. Many existing drugs for asthma and other lung diseases are specially formulated so they can be inhaled via either an inhaler, which sprays powdered particles of medication, or a nebulizer, which releases an aerosol containing the medication.

The MIT team set out to develop a material that could stabilize RNA during the process of aerosol delivery. Some previous studies have explored a material called polyethylenimine (PEI) for delivering inhalable DNA to the lungs. However, PEI doesn't break down easily, so with the repeated dosing that would likely be required for mRNA therapies, the polymer could accumulate and cause side effects.

To avoid those potential side effects, the researchers turned to a type of positively charged polymers called hyperbranched poly (beta amino esters), which, unlike PEI, are biodegradable.

The particles the team created consist of spheres, approximately 150 nanometers in diameter, with a tangled mixture of the polymer and mRNA molecules that encode luciferase, a bioluminescent protein. The researchers suspended these particles in droplets and delivered them to mice as an inhalable mist, using a nebulizer.

"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," Patel says.

The researchers found that 24 hours after the mice inhaled the mRNA, lung cells were producing the bioluminescent protein. The amount of protein gradually fell over time as the mRNA was cleared. The researchers were able to maintain steady levels of the protein by giving the mice repeated doses, which may be necessary if adapted to treat chronic lung disease.

Broad distribution

Further analysis of the lungs revealed that mRNA was evenly distributed throughout the five lobes of the lungs and was taken up mainly by epithelial lung cells, which line the lung surfaces. These cells are implicated in cystic fibrosis, as well as other lung diseases such as respiratory distress syndrome, which is caused by a deficiency in surfactant protein. In her new lab at Imperial College London, Patel plans to further investigate mRNA-based therapeutics.

In this study, the researchers also demonstrated that the nanoparticles could be freeze-dried into a powder, suggesting that it may be possible to deliver them via an inhaler instead of nebulizer, which could make the medication more convenient for patients.

TranslateBio, a company developing mRNA therapeutics, partially funded this study and has also begun testing an inhalable form of mRNA in a Phase 1/2 clinical trial in patients with cystic fibrosis. Other sources of funding for this study include the United Kingdom Engineering and Physical Sciences Research Council and the Koch Institute Support (core) Grant from the National Cancer Institute.

--

Reprinted with permission of MIT News

Neom, Saudi Arabia's $500 billion megacity, reaches its next phase

Construction of the $500 billion dollar tech city-state of the future is moving ahead.

Credit: Neom
Technology & Innovation
  • The futuristic megacity Neom is being built in Saudi Arabia.
  • The city will be fully automated, leading in health, education and quality of life.
  • It will feature an artificial moon, cloud seeding, robotic gladiators and flying taxis.
Keep reading Show less

Why do people believe in conspiracy theories?

Are we genetically inclined for superstition or just fearful of the truth?

Videos
  • From secret societies to faked moon landings, one thing that humanity seems to have an endless supply of is conspiracy theories. In this compilation, physicist Michio Kaku, science communicator Bill Nye, psychologist Sarah Rose Cavanagh, skeptic Michael Shermer, and actor and playwright John Cameron Mitchell consider the nature of truth and why some groups believe the things they do.
  • "I think there's a gene for superstition, a gene for hearsay, a gene for magic, a gene for magical thinking," argues Kaku. The theoretical physicist says that science goes against "natural thinking," and that the superstition gene persists because, one out of ten times, it actually worked and saved us.
  • Other theories shared include the idea of cognitive dissonance, the dangerous power of fear to inhibit critical thinking, and Hollywood's romanticization of conspiracies. Because conspiracy theories are so diverse and multifaceted, combating them has not been an easy task for science.

COVID-19 brain study to explore long-term effects of the virus

A growing body of research suggests COVID-19 can cause serious neurological problems.

Brain images of a patient with acute demyelinating encephalomyelitis.

Coronavirus
  • The new study seeks to track the health of 50,000 people who have tested positive for COVID-19.
  • The study aims to explore whether the disease causes cognitive impairment and other conditions.
  • Recent research suggests that COVID-19 can, directly or indirectly, cause brain dysfunction, strokes, nerve damage and other neurological problems.
Keep reading Show less
Sponsored by Charles Koch Foundation

Better reskilling can future-proof jobs in the age of automation. Enter SkillUp's new coalition.

Coronavirus layoffs are a glimpse into our automated future. We need to build better education opportunities now so Americans can find work in the economy of tomorrow.

Scroll down to load more…
Quantcast