Inhalable polymer nanoparticles for versatile mRNA delivery and mucosal vaccination.
| Autor: | 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 |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2022 Mar 23. Date of Electronic Publication: 2022 Mar 23. |
| DOI: | 10.1101/2022.03.22.485401 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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