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Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism

Author

Listed:
  • Zhijian Li

    (Stanford University)

  • Laura Amaya

    (Stanford University
    Stanford University School of Medicine)

  • Ruoxi Pi

    (Department of Medicine)

  • Sean K. Wang

    (Stanford University
    Stanford University School of Medicine)

  • Alok Ranjan

    (Stanford University)

  • Robert M. Waymouth

    (Stanford University)

  • Catherine A. Blish

    (Department of Medicine
    Chan Zuckerberg Biohub)

  • Howard Y. Chang

    (Stanford University
    Stanford University)

  • Paul A. Wender

    (Stanford University
    Stanford University)

Abstract

The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems.

Suggested Citation

  • Zhijian Li & Laura Amaya & Ruoxi Pi & Sean K. Wang & Alok Ranjan & Robert M. Waymouth & Catherine A. Blish & Howard Y. Chang & Paul A. Wender, 2023. "Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42672-x
    DOI: 10.1038/s41467-023-42672-x
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