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Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers

Author

Listed:
  • Jaclynn A. Meshanni

    (University of Pennsylvania Perelman School of Medicine
    University of Pennsylvania Perelman School of Medicine)

  • Emily R. Stevenson

    (Rutgers University)

  • Dapeng Zhang

    (East China University of Science and Technology)

  • Rachel Sun

    (Rutgers University)

  • Nathan A. Ona

    (University of Pennsylvania Perelman School of Medicine)

  • Erin K. Reagan

    (University of Pennsylvania Perelman School of Medicine)

  • Elena Abramova

    (Rutgers University)

  • Chang-Jiang Guo

    (Rutgers University)

  • Melissa Wilkinson

    (Rutgers University)

  • Ishana Baboo

    (University of Pennsylvania Perelman School of Medicine)

  • Yuzi Yang

    (East China University of Science and Technology)

  • Liuyan Pan

    (East China University of Science and Technology)

  • Devendra S. Maurya

    (University of Pennsylvania)

  • Virgil Percec

    (University of Pennsylvania)

  • Yongsheng Li

    (East China University of Science and Technology)

  • Andrew Gow

    (Rutgers University)

  • Drew Weissman

    (University of Pennsylvania Perelman School of Medicine
    University of Pennsylvania Perelman School of Medicine)

  • Elena N. Atochina-Vasserman

    (University of Pennsylvania Perelman School of Medicine
    University of Pennsylvania Perelman School of Medicine)

Abstract

Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways, such as treatment with nebulized instillation and inhalation. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we show the development of an mRNA therapeutic for the lower lung in mice using one-component Ionizable Amphiphilic Janus Dendrimers as a delivery vehicle. We deliver an anti-inflammatory cytokine mRNA, transforming growth factor-beta, to produce transient protein expression in the lower regions of the lung. This study highlights a method for precise, effective, and safe delivery of TGF-β mRNA to the lung in mice. This delivery system offers a promising approach for targeting therapeutics to the specific tissues, a strategy necessary to fill the current clinical gap in treating parenchymal lung injury and disease.

Suggested Citation

  • Jaclynn A. Meshanni & Emily R. Stevenson & Dapeng Zhang & Rachel Sun & Nathan A. Ona & Erin K. Reagan & Elena Abramova & Chang-Jiang Guo & Melissa Wilkinson & Ishana Baboo & Yuzi Yang & Liuyan Pan & D, 2025. "Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56448-y
    DOI: 10.1038/s41467-025-56448-y
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