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Enhanced lipid-polymer nanoparticle could boost inhalable mRNA therapies

Nanotechnology

Business Honor
14 November, 2024

A new lipid-polymer nanoparticle stabilizes mRNA for inhalation, paving the way for respiratory disease treatments

A study published in the Journal of the American Chemical Society highlights progress toward making inhalable mRNA therapies a reality. The researchers present an enhanced lipid-polymer nanoparticle designed to protect mRNA during nebulization, enabling it to be successfully aerosolized and delivered to the lungs of mice.

mRNA medicines, which encode proteins in order to treat or prevent disease, such as lung conditions. A major challenge is the fragility of mRNA and its inability to easily enter cells without the help of particles. Lipid nanoparticles are fat-based, tiny particles that protect and transport the mRNA to target cells. Previous generations of these nanoparticles were unstable when aerosolized, clumping together and rendering them ineffective for inhalation.

The scientists Daniel Anderson and Allen Jiang conducted a study on zwitterionic polymers-polymer that carries both positive and negative charges. They discovered that upon incorporating these polymers within lipid nanoparticles, they would be stable upon nebulization. The scientists formulated nanoparticles using phospholipids, cholesterol, ionizable lipids, and zwitterionic polymers that resulted in highly efficient delivery of mRNA without its size alteration while misted.

In animal trials, the optimized formulation of the nanoparticles transported mRNA into mouse lungs quite efficiently. Once again, the nanoparticles produced the fluorescence-producing protein without causing any inflammation. However, the same delivery method worked in mice with mucus-lined airways, simulating cystic fibrosis and such similar conditions.

This opens up completely new paths of potential development in the generation of an inhalable mRNA therapy specifically in respiratory diseases. The researchers will test the system on larger animals. The authors of this work have patented the technology, and some of them are also founders of biotech companies: oRNA Therapeutics and Moderna that deal with RNA and mRNA medicines.