Kim, Junghyun Jeon, Seulgi Kang, Seong Jae Kim, Kyoung-Ran Hien Bao Dieu Thai Lee, Seokyung Kim, Sehoon Lee, Yun-Sil Ahn, Dae-Ro 2024-01-19T17:30:44Z 2024-01-19T17:30:44Z 2022-01-10 2020-06-10 0168-3659 https://pubs.kist.re.kr/handle/201004/118520 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. English ELSEVIER GROWTH-FACTOR-BETA MOLECULAR-MECHANISMS CYTOTOXICITY BLEOMYCIN PATHOGENESIS PEPTIDES DISEASE INJURY MICE Lung-targeted delivery of TGF-beta antisense oligonucleotides to treat pulmonary fibrosis Article 10.1016/j.jconrel.2020.03.016 1 JOURNAL OF CONTROLLED RELEASE, v.322, pp.108 - 121 JOURNAL OF CONTROLLED RELEASE 322 108 121 scie scopus 000537134600001 2-s2.0-85081743001 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article GROWTH-FACTOR-BETA MOLECULAR-MECHANISMS CYTOTOXICITY BLEOMYCIN PATHOGENESIS PEPTIDES DISEASE INJURY MICE Pulmonary fibrosis Polymeric antisense oligonucleotides Human beta-defensin Rolling circle amplification