mRNA delivery enabled by metal–organic nanoparticles

Yuang Gu, Jingqu Chen, Zhaoran Wang, Chang Liu, Tianzheng Wang, Chan-Jin Kim, Helena Durikova, Soraia Fernandes, Darryl N. Johnson, Robert De Rose, Christina Cortez-Jugo and Frank Caruso ()
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Yuang Gu: The University of Melbourne
Jingqu Chen: The University of Melbourne
Zhaoran Wang: The University of Melbourne
Chang Liu: The University of Melbourne
Tianzheng Wang: The University of Melbourne
Chan-Jin Kim: The University of Melbourne
Helena Durikova: The University of Melbourne
Soraia Fernandes: The University of Melbourne
Darryl N. Johnson: The University of Melbourne
Robert De Rose: The University of Melbourne
Christina Cortez-Jugo: The University of Melbourne
Frank Caruso: The University of Melbourne

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract mRNA therapeutics are set to revolutionize disease prevention and treatment, inspiring the development of platforms for safe and effective mRNA delivery. However, current mRNA delivery platforms face some challenges, including limited organ tropism for nonvaccine applications and inflammation induced by cationic nanoparticle components. Herein, we address these challenges through a versatile, noncationic nanoparticle platform whereby mRNA is assembled into a poly(ethylene glycol)-polyphenol network stabilized by metal ions. Screening a range of components and relative compositional ratios affords a library of stable, noncationic, and highly biocompatible metal–organic nanoparticles with robust mRNA transfection in vitro and in mice. Intravenous administration of the lead mRNA-containing metal–organic nanoparticles enables predominant protein expression and gene editing in the brain, liver, and kidney, while organ tropism is tuned by varying nanoparticle composition. This study opens an avenue for realizing metal–organic nanoparticle-enabled mRNA delivery, offering a modular approach to assembling mRNA therapeutics for health applications.

Date: 2024
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DOI: 10.1038/s41467-024-53969-w

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