A groundbreaking study introduces stable inhalable mRNA treatment using nanoparticles that hold up during nebulization, showing significant potential in treating lung diseases without injections.
Many people dislike getting shots for treatments or vaccines, so scientists are exploring ways to develop medicines, like those made from messenger RNA (mRNA), that can be inhaled instead. A new study published today (November 13) in the Journal of the American Chemical Society highlights key progress toward creating inhalable mRNA therapies. Researchers describe their advanced lipid-polymer nanoparticle that can hold mRNA in a stable form for nebulization and deliver it effectively as aerosol droplets to the lungs of mice.
Challenges in mRNA Delivery
mRNA medicines work by encoding proteins that could help treat or prevent various diseases, including those affecting the lungs. However, these proteins are fragile and cannot penetrate cells on their own. To protect and deliver mRNA to lung cells, scientists use lipid nanoparticles—tiny fatty spheres that act like “suitcases,” carrying the mRNA safely to its target.
Yet, early versions of these lipid nanoparticles were unsuitable for inhalable treatments, as they tended to clump together or expand in size when sprayed. Previous efforts to solve this issue involved adding polymers, like polyethylene glycol, to the lipid particles. However, this approach did not provide sufficient stability for effective nebulized delivery.
Innovative Solution With Zwitterionic Polymers
Now, Daniel Anderson, Allen Jiang, Sushil Lathwal, and colleagues have hypothesized that a different type of polymer, one with repeating units of positively and negatively charged components called a zwitterionic polymer, could create mRNA-containing lipid nanoparticles that can withstand nebulization (turning a liquid into a mist).
The researchers synthesized a variety of lipid nanoparticles out of four ingredients: a phospholipid, cholesterol, an ionizable lipid, and lipids of different lengths attached to zwitterionic polymers of various lengths. Initial tests indicated that many of the resulting lipid nanoparticles efficiently held mRNA and didn’t change size during misting or after being misted.
Effective mRNA Delivery in Animal Trials
Then in animal trials, the researchers determined that a lower-cholesterol version of the lipid nanoparticles with zwitterionic polymers was the optimal formulation for aerosol delivery. When transporting an mRNA encoding a luminescent protein, this nanoparticle produced the highest luminescence within the animals’ lungs and a uniform protein expression in the tissues, thereby demonstrating that it had the best ability to deliver inhaled mRNA.
Mice given three airborne doses of the optimal nanoparticle over a 2-week period maintained consistent luminescent protein production without experiencing measurable inflammation in the lungs. The delivery method even worked in mice with a thick layer of mucus lining their airways, which was meant to model the lungs of people with cystic fibrosis.
Taken together, the researchers say this set of results demonstrates the successful airborne delivery of mRNA using zwitterionic polymers in lipid nanoparticles. As a next step, they plan to conduct tests in larger animals.
Reference: “Zwitterionic Polymer-Functionalized Lipid Nanoparticles for the Nebulized Delivery of mRNA” by Allen Y. Jiang, Sushil Lathwal, Sabrina Meng, Jacob Witten, Emily Beyer, Patrick McMullen, Yizong Hu, Rajith S. Manan, Idris Raji, Robert Langer and Daniel G. Anderson, 13 November 2024, Journal of the American Chemical Society.
DOI: 10.1021/jacs.4c11347
The authors acknowledge funding from the U.S. National Institutes of Health, Sanofi (formerly Translate Bio), the Cystic Fibrosis Foundation, the Massachusetts Institute of Technology Undergraduate Research Opportunities Program, and the Koch Institute Support (core) Grant from the National Cancer Institute.
The authors have filed a patent on this technology. Some authors are founders of oRNA Therapeutics and Moderna, biotechnology companies that produce RNA and mRNA medicines, respectively.
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11 Comments
“Revolutionize medicine”? It’s just one disease you’re talking about, for crying out loud!
If you mean COVID, it was an unfortunate rollout for the new technology. At great expense with constant reinjections, it failed to produce any durable immunity to the disease, let alone eradicate COVID, which now spreads unchecked and is as scary as the common cold. mRNA vaccines still have a lot of potential as a technology. Its rapid development cycle could mean effective custom immunotherapies against cancer, for example.
Needles have an infection risk, and need skilled administration, and people avoid them. Aerosolizing it could make deployment better. That said, to me it sounds more like a futuristic undetectable bio-weapon than a handy treatment.
Saying the name of a recent virus seems to trigger the SPAM filter for moderation. That’s a bad sign….no wonder you didn’t say the name disease. My previous reply number 864619 may appear eventually.
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If you mean That 2019 Virus, it was an unfortunate rollout for the new technology. At great expense with constant reinjections, it failed to produce any durable immunity to the disease, let alone eradicate That 2019 Virus, which now spreads unchecked and is as scary as the common cold. mRNA vaccines still have a lot of potential as a technology. Its rapid development cycle could mean effective custom immunotherapies against cancer, for example.
Needles have an infection risk, and need skilled administration, and people avoid them. Aerosolizing it could make deployment better. However, to me it sounds more like a futuristic undetectable attack than a handy treatment.
When you say that “mRNA vaccine technology has a lot of potential”, I wonder if you’re aware that, save for COVID, not a single mRNA for any other known disease has even completed the clinical trial phase, let alone been rolled out for a widespread use.
In other words, the mRNA technology is one giant failure, despite being around for a couple of decades. For COVID they brazenly rushed it out of the lab, skipped a lot of safety steps to do it – and we’re lucky they didn’t kill or incapacitate millions with it but “only” tens of thousands.
Absolutely agreed. Potential, not actual. I think it still has that potential as a technology, but a usage of it was definitely rushed out the door for the disease that dare not speak its name. With the state of the data and scientific curiosity on the matter, I’m not convinced millions weren’t harmed or killed. Anyone who will ever want funding for anything seems to have their fingers in their ears.
I think the first mRNA vaccine proof of concept was in 1989, and first trials in humans in 2013. The standard egg-incubated vaccines are cheap and easy, and the diseases an mRNA vaccine could target are very profitable, so I think development wasn’t a priority when it takes decades anyway. With the euphemistic ‘acceleration’ of mRNA vaccines for the unnameable disease, I at least hope the technology advanced and was funded to where it might actually realize some of its potential. Some good should come from this, somehow, I have to hope.
My reply took did show up eventually — unsure what I said triggering that. I displeased our SciTechDaily gods, temporarily.
Hi,
Your comment was temporarily put into pending because it included “kill.” We definitely don’t want to censor comments, but we’ve had to adjust our moderation settings recently due to past instances of Google demonetizing us.
Our SciTechDaily gods walk among us! Thanks Colin, totally understandable, gotta make a living. I appreciate I can comment here without registering with an app, making SciTechDaily the way the Internet is supposed to be. I can just cull or denature viruses with my thesaurus.
One way or another you’re hell bent and determined to get this DNA altering myocarditis causing BS into everyone! Thankfully more people are awake to what you idiots are trying to do to mankind!
It didn’t take long for this “SPAM” to show up.
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