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[Preprint]. 2022 Mar 23:2022.03.22.485401.
doi: 10.1101/2022.03.22.485401.

Inhalable polymer nanoparticles for versatile mRNA delivery and mucosal vaccination

Alexandra Suberi, Molly K Grun, Tianyang Mao, Benjamin Israelow, Melanie Reschke, Julian Grundler, Laiba Akhtar, Teresa Lee, Kwangsoo Shin, Alexandra S Piotrowski-Daspit, Robert J Homer, Akiko Iwasaki, Hee Won Suh, W Mark Saltzman

Inhalable polymer nanoparticles for versatile mRNA delivery and mucosal vaccination

Alexandra Suberi et al. bioRxiv. .

Update in

  • Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination.
    Suberi A, Grun MK, Mao T, Israelow B, Reschke M, Grundler J, Akhtar L, Lee T, Shin K, Piotrowski-Daspit AS, Homer RJ, Iwasaki A, Suh HW, Saltzman WM. Suberi A, et al. Sci Transl Med. 2023 Aug 16;15(709):eabq0603. doi: 10.1126/scitranslmed.abq0603. Epub 2023 Aug 16. Sci Transl Med. 2023. PMID: 37585505 Free PMC article.

Abstract

An inhalable platform for mRNA therapeutics would enable minimally invasive and lung targeted delivery for a host of pulmonary diseases. Development of lung targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung. We optimized biodegradable poly(amine-co-ester) polyplexes for mRNA delivery using end group modifications and polyethylene glycol. Our polyplexes achieved high transfection of mRNA throughout the lung, particularly in epithelial and antigen-presenting cells. We applied this technology to develop a mucosal vaccine for SARS-CoV-2. Intranasal vaccination with spike protein mRNA polyplexes induced potent cellular and humoral adaptive immunity and protected K18-hACE2 mice from lethal viral challenge.

One-sentence summary: Inhaled polymer nanoparticles (NPs) achieve high mRNA expression in the lung and induce protective immunity against SARS-CoV-2.

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