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

Yoonsung Song, Ye Ram Kim, So Mi Kim, Qurrat Ul Ain, Kiseok Jang, Chul Su Yang, Yong-Hee Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Elevated level of tumor necrosis factor-α (TNF-α), one of the inflammatory cytokines, is considered to be a potential target for the inflammatory bowel disease (IBD) therapy. Recently, TNF-α converting enzyme (TACE), a sheddase playing an important role in cleaving and releasing bioactive soluble TNF-α, has been challenged with inhibitors to treat inflammatory diseases. Here, we report a novel anti-TNF-α 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-α 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.

Original languageEnglish
Pages (from-to)231-241
Number of pages11
JournalJournal of Controlled Release
Volume239
DOIs
StatePublished - 2016 Oct 10

Fingerprint

Colitis
RNA Interference
Down-Regulation
Tumor Necrosis Factor-alpha
Small Interfering RNA
Enzymes
Arginine
Ulcerative Colitis
Inflammatory Bowel Diseases
Disulfides
Colon
Cytokines
Safety
Therapeutics
Genes

Keywords

  • Inflammatory bowel disease
  • RNA interference
  • TNF-α converting enzyme
  • Tumor necrosis factor-α

Cite this

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title = "RNAi-mediated silencing of TNF-α converting enzyme to down-regulate soluble TNF-α production for treatment of acute and chronic colitis",
abstract = "Elevated level of tumor necrosis factor-α (TNF-α), one of the inflammatory cytokines, is considered to be a potential target for the inflammatory bowel disease (IBD) therapy. Recently, TNF-α converting enzyme (TACE), a sheddase playing an important role in cleaving and releasing bioactive soluble TNF-α, has been challenged with inhibitors to treat inflammatory diseases. Here, we report a novel anti-TNF-α 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-α 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.",
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RNAi-mediated silencing of TNF-α converting enzyme to down-regulate soluble TNF-α production for treatment of acute and chronic colitis. / Song, Yoonsung; Kim, Ye Ram; Kim, So Mi; Ul Ain, Qurrat; Jang, Kiseok; Yang, Chul Su; Kim, Yong-Hee.

In: Journal of Controlled Release, Vol. 239, 10.10.2016, p. 231-241.

Research output: Contribution to journalArticle

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AU - Yang, Chul Su

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