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Lung-targeted delivery of TGF-beta antisense oligonucleotides to treat pulmonary fibrosis
- Title
- Lung-targeted delivery of TGF-beta antisense oligonucleotides to treat pulmonary fibrosis
- Authors
- Kim, Junghyun; Jeon, Seulgi; Kang, Seong Jae; Kim, Kyoung-Ran; Hien Bao Dieu Thai; Lee, Seokyung; Kim, Sehoon; Lee, Yun-Sil; Ahn, Dae-Ro
- Ewha Authors
- 이윤실
- SCOPUS Author ID
- 이윤실
- Issue Date
- 2020
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- ISSN
- 0168-3659
1873-4995
- Citation
- JOURNAL OF CONTROLLED RELEASE vol. 322, pp. 108 - 121
- Keywords
- Pulmonary fibrosis; Polymeric antisense oligonucleotides; Human beta-defensin; Rolling circle amplification
- Publisher
- ELSEVIER
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Pulmonary fibrosis is a serious respiratory disease, with limited therapeutic options. Since TGF-beta is a critical factor in the fibrotic process, downregulation of this cytokine has been considered a potential approach for disease treatment. Herein, we designed a new lung-targeted delivery technology based on the complexation of polymeric antisense oligonucleotides (pASO) and dimeric human beta-defensin 23 (DhBD23). Antisense oligonucleotides targeting TGF-beta mRNA were polymerized by rolling circle amplification and complexed with DhBD23. After complexation with DhBD23, pASO showed improved serum stability and enhanced uptake by fibroblasts in vitro and lung-specific accumulation upon intravenous injection in vivo. The pASO/DhBD23 complex delivered into the lung downregulated target mRNA, and subsequently alleviated lung fibrosis in mice, as demonstrated by western blotting, quantitative reverse-transcriptase PCR (qRT-PCR), immunohistochemistry, and immunofluorescence imaging. Moreover, as the complex was prepared only with highly biocompatible materials such as DNA and human-derived peptides, no systemic toxicity was observed in major organs. Therefore, the pASO/DhBD23 complex is a promising gene therapy platform with lung-targeting ability to treat various pulmonary diseases, including pulmonary fibrosis, with low side effects.
- DOI
- 10.1016/j.jconrel.2020.03.016
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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