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An advance toward inhalable mRNA medications, vaccines

Date:
November 13, 2024
Source:
American Chemical Society
Summary:
Most people don't enjoy getting shots for treatments or vaccines. So, researchers are working to create more medicines, such as those made from messenger RNA (mRNA), that can be sprayed and inhaled. A study reports steps toward making inhalable mRNA medicines a possibility. Researchers outline their improved lipid-polymer nanoparticle for holding mRNA that is stable when nebulized and successfully delivers aerosols (liquid droplets) in mice's lungs.
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Most people don't enjoy getting shots for treatments or vaccines. So, researchers are working to create more medicines, such as those made from messenger RNA (mRNA), that can be sprayed and inhaled. A study in the Journal of the American Chemical Society reports steps toward making inhalable mRNA medicines a possibility. Researchers outline their improved lipid-polymer nanoparticle for holding mRNA that is stable when nebulized and successfully delivers aerosols (liquid droplets) in mice's lungs.

mRNA medicines encode proteins that could treat or prevent a variety of illnesses, including lung diseases. However, these proteins are delicate and can't enter cells by themselves. To get intact mRNA inside lung cells, tiny fatty spheres (known as lipid nanoparticles) can be used like suitcases to store and transport the components until they reach their final destination. However, early versions of fatty spheres for mRNA delivery won't work for inhalable medications because the nanoparticles clump together or increase in size when sprayed into the air. To try to address this problem, previous researchers attached a polymer, such as polyethylene glycol, onto one of the particle's fatty components, but this didn't stabilize the resulting lipid nanoparticles enough.

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.

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.

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.


Story Source:

Materials provided by American Chemical Society. Note: Content may be edited for style and length.


Journal Reference:

  1. Allen Y. Jiang, Sushil Lathwal, Sabrina Meng, Jacob Witten, Emily Beyer, Patrick McMullen, Yizong Hu, Rajith S. Manan, Idris Raji, Robert Langer, Daniel G. Anderson. Zwitterionic Polymer-Functionalized Lipid Nanoparticles for the Nebulized Delivery of mRNA. Journal of the American Chemical Society, 2024; DOI: 10.1021/jacs.4c11347

Cite This Page:

American Chemical Society. "An advance toward inhalable mRNA medications, vaccines." ScienceDaily. ScienceDaily, 13 November 2024. <www.sciencedaily.com/releases/2024/11/241113123540.htm>.
American Chemical Society. (2024, November 13). An advance toward inhalable mRNA medications, vaccines. ScienceDaily. Retrieved November 20, 2024 from www.sciencedaily.com/releases/2024/11/241113123540.htm
American Chemical Society. "An advance toward inhalable mRNA medications, vaccines." ScienceDaily. www.sciencedaily.com/releases/2024/11/241113123540.htm (accessed November 20, 2024).

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