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mRNA delivery enabled by metal–organic nanoparticles

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Frank Caruso, 2024. "mRNA delivery enabled by metal–organic nanoparticles," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53969-w
    DOI: 10.1038/s41467-024-53969-w
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    References listed on IDEAS

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    1. Mikhail E. Matlashov & Daria M. Shcherbakova & Jonatan Alvelid & Mikhail Baloban & Francesca Pennacchietti & Anton A. Shemetov & Ilaria Testa & Vladislav V. Verkhusha, 2020. "A set of monomeric near-infrared fluorescent proteins for multicolor imaging across scales," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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