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

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 and Elena N. Atochina-Vasserman ()
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Jaclynn A. Meshanni: 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
Elena N. Atochina-Vasserman: University of Pennsylvania Perelman School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-56448-y

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