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RNAi-mediated silencing of TNF-alpha converting enzyme to down-regulate soluble TNF-alpha production for treatment of acute and chronic colitis

Title
RNAi-mediated silencing of TNF-alpha converting enzyme to down-regulate soluble TNF-alpha production for treatment of acute and chronic colitis
Author
양철수
Keywords
RNA interference; Tumor necrosis factor-alpha; TNF-alpha converting enzyme; Inflammatory bowel disease
Issue Date
2016-10
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v. 239, Page. 231-241
Abstract
Elevated level of tumor necrosis factor-alpha (TNF-alpha), one of the inflammatory cytokines, is considered to be a potential target for the inflammatory bowel disease (IBD) therapy. Recently, TNF-alpha converting enzyme (TACE), a sheddase playing an important role in cleaving and releasing bioactive soluble TNF-alpha, has been challenged with inhibitors to treat inflammatory diseases. Here, we report a novel anti-TNF-alpha strategy using a short hairpin RNA silencing TACE (shTACE) to prevent and treat colitis. The shTACE formed stable complexes with nona-arginine-based bio-cleavable disulfide bond-linked poly (arginine) (PAs-s) for enhanced gene delivery. Systemically administered shTACE/PAs-s peptoplexes efficiently decreased TNF-alpha levels, increased survival and alleviated pathophysiological parameters representing colitis severity. Our results demonstrate effectiveness and safety of shTACE/PAs-s peptoplexes with the capacity of overcoming acute and chronic ulcerative colitis through modulation of excessive inflammatory responses in the colon, providing a strong potential as a therapeutic agent for a broad variety of inflammatory diseases. (C) 2016 Elsevier B.V. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0168365916305351?via%3Dihubhttp://repository.hanyang.ac.kr/handle/20.500.11754/100455
ISSN
0168-3659; 1873-4995
DOI
10.1016/j.jconrel.2016.08.017
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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