Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers
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.
Authors
- Devendra S. Maurya (ORCID: https://orcid.org/0000-0002-4488-9927)
- Andrew J. Gow (ORCID: https://orcid.org/0000-0003-0876-5158)
- Emily Stevenson (ORCID: https://orcid.org/0000-0003-1329-8734)
- Erin K. Reagan (ORCID: https://orcid.org/0000-0003-3162-4636)
- Nathan Ona (ORCID: https://orcid.org/0000-0002-8729-2223)
- Rachel Sun
- Changjiang Guo (ORCID: https://orcid.org/0000-0002-7447-3762)
- Elena N. Atochina‐Vasserman (ORCID: https://orcid.org/0000-0001-7950-7004)
- J. Meshanni (ORCID: https://orcid.org/0000-0002-1491-3594)
- Елена Владимировна Абрамова (ORCID: https://orcid.org/0000-0002-4249-8033)
- Drew Weissman (ORCID: https://orcid.org/0000-0002-1501-6510)
- Ishana Baboo
- Melissa L. Wilkinson (ORCID: https://orcid.org/0000-0002-3482-3975)
- Virgil Percec (ORCID: https://orcid.org/0000-0001-5926-0489)
- Dapeng Zhang (ORCID: https://orcid.org/0000-0003-4222-6107)
- Yongsheng Li (ORCID: https://orcid.org/0000-0001-5621-9528)
- Yuzi Yang
- Liuyan Pan
Institutions
- Rutgers, The State University of New Jersey (US)
- East China University of Science and Technology (CN)
- Environmental and Occupational Health Sciences Institute (US)
- Penn Center for AIDS Research (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-21
- DOI
- https://doi.org/10.1038/s41467-025-56448-y
- Citations
- 32
- Primary Topic
- Inhalation and Respiratory Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 48.59
Funders
- National Institute of Environmental Health Sciences