Journal Article Epublish 3 citations
PubMed: 39984450 DOI: 10.1038/s41467-025-56448-y
Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers.
Nat Commun 16(1):1806
Authors: 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
Affiliations
- Penn Institute for RNA Innovation, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
- Infectious Disease Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
- Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ, USA.
- School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, China.
- Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
- Penn Institute for RNA Innovation, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
- Infectious Disease Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
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.
MeSH
Lung, Biological Science Disciplines, Dendrimers, Lung Injury, Rna, Messenger, Therapeutics