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使用单组分可电离两亲性Janus树枝状大分子将转化生长因子-β mRNA靶向递送至肺实质。

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

作者信息

Atochina-Vasserman Elena, Meshanni Jaclynn, Stevenson Emily, Zhang Dapeng, Sun Rachel, Ona Nathan, Reagan Erin, Abramova Elena, Guo Chang-Jiang, Wilkinson Melissa, Baboo Ishana, Yang Yuzi, Pan Liuyan, Maurya Devendra, Percec Virgil, Li Yongsheng, Gow Andrew, Weissman Drew

机构信息

Perelman School of Medicine, University of Pennsylvania.

University of Pennsylvania.

出版信息

Res Sq. 2024 Jul 12:rs.3.rs-4656663. doi: 10.21203/rs.3.rs-4656663/v1.

DOI:10.21203/rs.3.rs-4656663/v1
PMID:39041040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11261981/
Abstract

Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we have developed an mRNA therapeutic for the lower lung using one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a delivery vehicle. We deliver an anti-inflammatory cytokine mRNA, transforming growth factor-beta (TGF-β), to produce transient protein expression in the lower regions of the lung. This study highlights IAJD's potential for precise, effective, and safe delivery of TGF-β mRNA to the lung. 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.

摘要

目前将肺部治疗药物输送到肺部的临床策略主要针对气道的上部。然而，对于实质性肺损伤和疾病的治疗，将药物靶向递送至肺的下部区域是必要的。在此，我们开发了一种用于下肺的mRNA疗法，使用单组分可电离两亲性Janus树枝状大分子（IAJD）作为递送载体。我们递送一种抗炎细胞因子mRNA，即转化生长因子-β（TGF-β），以在肺的下部区域产生瞬时蛋白表达。这项研究突出了IAJD将TGF-β mRNA精确、有效且安全地递送至肺部的潜力。这种递送系统为将治疗药物靶向特定组织提供了一种有前景的方法，这是填补目前治疗实质性肺损伤和疾病临床空白所需的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/7ab94ac1eceb/nihpp-rs4656663v1-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/ffbc26b17a27/nihpp-rs4656663v1-f0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/75c4f4b5d1bb/nihpp-rs4656663v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/f755e92c24c5/nihpp-rs4656663v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/8fdb67e8b3a1/nihpp-rs4656663v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/e1c575f81f8e/nihpp-rs4656663v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/7ab94ac1eceb/nihpp-rs4656663v1-f0010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/880104621768/nihpp-rs4656663v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/5306401cab3e/nihpp-rs4656663v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/f6fe7ee814db/nihpp-rs4656663v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/2261c7cea1ae/nihpp-rs4656663v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/75c4f4b5d1bb/nihpp-rs4656663v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/f755e92c24c5/nihpp-rs4656663v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/8fdb67e8b3a1/nihpp-rs4656663v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/e1c575f81f8e/nihpp-rs4656663v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c0a/11261981/7ab94ac1eceb/nihpp-rs4656663v1-f0010.jpg

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