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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月21日

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  • 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,
  • Devendra S. Maurya,
  • Virgil Percec,
  • Yongsheng Li,
  • Andrew Gow,
  • Drew Weissman,
  • Elena N. Atochina-Vasserman

摘要

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.