Author: Qiu, Yingshan; Lam, Jenny K. W.; Leung, Susan W. S.; Liang, Wanling
Title: Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside Document date: 2016_9_20
ID: 04pp3lv0_74
Snippet: One complication of using TGF-β as the molecular target of RNAi is related to its physiological role in maintaining immune and cellular homeostasis. It has a role in tumor suppression as suggested by the finding that specific inhibition of TGF-β in mouse stromal fibroblasts results in spontaneous carcinoma formation in the adjacent epithelium [226] . As a result, targeting the downstream effectors of TGF-β may offer the therapeutic benefit of .....
Document: One complication of using TGF-β as the molecular target of RNAi is related to its physiological role in maintaining immune and cellular homeostasis. It has a role in tumor suppression as suggested by the finding that specific inhibition of TGF-β in mouse stromal fibroblasts results in spontaneous carcinoma formation in the adjacent epithelium [226] . As a result, targeting the downstream effectors of TGF-β may offer the therapeutic benefit of inhibiting the TGF-β-mediated fibrotic response while preserving the major physiological function of the profibrotic cytokine [227] . CTGF is a key molecule that regulates fibroblast mitosis and promotes collagen deposition in pulmonary fibrosis induced by TGF-β. A non-viral delivery system consists of poly(dimethylamino)ethylmethacrylate (PDMAEMA) and its copolymer with poly(methylether-methacrylate-ethyleneglycol) [PMAPEG] was used to incorporate and form complexes with siRNA targeting CTGF. After intratracheal administration, significant reduction of CTGF expression, collagen deposition and inflammatory cytokines (IL-6, TNF-α and TGF-β) production were observed in bleomycin-induced lung fibrosis animal model. More importantly, the survival rate of the animals treated with siRNA targeting CTGF was significantly increased in comparison with the group treated with scrambled siRNA [225] .
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