文献类型：期刊文献

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

作者：Meshanni, Jaclynn A.[1,2];Stevenson, Emily R.[3];Zhang, Dapeng[4];Sun, Rachel[3];Ona, Nathan A.[1];Reagan, Erin K.[1];Abramova, Elena[3];Guo, Chang-Jiang[3];Wilkinson, Melissa[3];Baboo, Ishana[1];Yang, Yuzi[4];Pan, Liuyan[4];Maurya, Devendra S.[5];Percec, Virgil[5];Li, Yongsheng[4];Gow, Andrew[3];Weissman, Drew[1,2];Atochina-Vasserman, Elena N.[1,2]

机构：[1]Univ Penn, Perelman Sch Med, Penn Inst RNA Innovat, Philadelphia, PA 19104 USA;[2]Univ Penn, Perelman Sch Med, Dept Med, Infect Dis Div, Philadelphia, PA 19104 USA;[3]Rutgers State Univ, Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA;[4]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai, Peoples R China;[5]Univ Penn, Dept Chem, Philadelphia, PA USA

年份：2025

卷号：16

期号：1

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001428315400017)】；

基金：The authors thank Drs. Yangzhu Du, Honghong Sun, and Eline Luning Prak of the Human Immunology Core (supported in part by NIH P30 AI045008 and P30 CA016520. HIC RRID: SCR_022380) at the Perelman School of Medicine at the University of Pennsylvania for their assistance with Luminex assays. They also would also like to thank Drs. Michael Goedken and Marianne Polunas of the Rutgers University Histology Core for their assistance with histological preparation and pathology services; Jessica Cervelli and Rita Hahn of the Rutgers Flow Cytometry Core for assistance with flow cytometry. In addition, they thank Sungjae Lee, Tony Hu, and Houping Ni for their technical assistance. They also express gratitude to Dr. Yongfeng Zhou at Shanghai Jiao Tong University for his assistance with cryo-TEM imaging of formulated IAJD34. Special thanks to Dr. Wook-Jin Park and Jessica A. Vasserman for their help with the characterization of formulated particles (size, PDI, Zeta potential, and encapsulation efficiency). Financial support was provided by the "National Institutes of Health National Institute of Environmental Health Sciences [Grant T32-ES01984] and [Grant P30-ES005022] for A.J.G., E.R.S, R.S., M.W., E.A., and C.J.G. NSF-DMR-1807127, 1720530, and 2104554 financially supported V.P. This work was partially supported by the Wellcome Leap R3 program.

语种：英文

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-beta 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.