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Drug delivery

Inhalable polymer delivers RNA to the lungs

Nature Reviews Bioengineering volume 1, page 4 (2023)Cite this article

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Nucleic acid therapeutics and preventives, for example, mRNA vaccines, require delivery by nanoparticles to protect nucleic acids and to allow their cellular update. For example, lipid nanoparticles have enabled the systemic administration of COVID-19 mRNA vaccines. However, the treatment of respiratory virus infections would greatly benefit from nucleic acid administration directly into the lungs by inhalation. Lung delivery of nucleic acids could further improve the treatment of other pulmonary pathogens and diseases, such as influenza and cystic fibrosis. Now, writing in Nature Materials, Philip J. Santangelo and team identified a polymeric nanoparticle, based on a poly-β-amino-thio-ester, that can be inhaled to deliver nucleic acids into the lungs of various animal species, regardless of cargo size and complexity.

As an alternative to lipid nanoparticles, Santangelo and colleagues have explored polymeric nanoparticles for lung delivery. The team has previously demonstrated that poly-β-amino-esters (PBAEs) are particularly suited to inhalable delivery of nucleic acids. Building on this work, they now used a combinatorial synthesis strategy with a nebulizer-based particle screening system to assess 166 PBAEs and PBAE-containing formulations in mice. “We developed sensitive reporter mRNAs and a nose-only delivery system that allowed us to rapidly screen many polymer chemistries, because we could use very small amounts of mRNA and polymer for testing,“ explains Santangelo.

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  1. Nature Reviews Bioengineering https://www.nature.com/natrevbioeng/

    Christine-Maria Horejs

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  1. Christine-Maria Horejs
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Correspondence to Christine-Maria Horejs.

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Horejs, CM. Inhalable polymer delivers RNA to the lungs. Nat Rev Bioeng 1, 4 (2023). https://doi.org/10.1038/s44222-022-00018-0

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