Selected article for: "experimental model and gene expression"

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_57
    Snippet: Tyrosine kinases, which are broadly classified into receptor and non-receptor types, play an important role in activating the transcription factors for inflammatory gene expression upon activation by the inflammatory signals [194, 195] . The key receptor tyrosine kinases involved in the inflammatory response in asthma include epidermal growth factor receptor (EGFR), c-kit (a stem cell factor receptor) and vascular endothelial growth factor recept.....
    Document: Tyrosine kinases, which are broadly classified into receptor and non-receptor types, play an important role in activating the transcription factors for inflammatory gene expression upon activation by the inflammatory signals [194, 195] . The key receptor tyrosine kinases involved in the inflammatory response in asthma include epidermal growth factor receptor (EGFR), c-kit (a stem cell factor receptor) and vascular endothelial growth factor receptor (VEGFR), while the non-receptor forms are spleen tyrosine kinase (Syk), Src and janus kinase (JAK) [196] . Syk is a pivotal intracellular signaling molecule involved in the activation of several pro-inflammatory transcription factors [197] . Inhibition of Syk expression by antisense oligonucleotides has proven effective in suppression of tracheal contraction and pulmonary inflammation in animal models of OVA-induced asthma [198] . When naked siRNA targeting Syk was administered to the lungs of allergen-induced asthma mice model via nasal instillation, the recruitment of inflammatory cells in the BALF was reduced [194] . Similarly, intranasal administration of siRNA targeting c-kit also induced a promising result in reducing mucus secretion and airway inflammation in experimental asthma mouse model [173] . Moreover, clinical studies have been performed on a siRNA targeting Syk (Excellairâ„¢ developed by ZaBeCor Pharmaceuticals, USA) for the treatment of asthma. In the Phase I study, 75% of asthma patients receiving Excellairâ„¢ by inhalation for 21 consecutive days showed improvement in breathing or reduced the usage of rescue inhaler compared to placebo. The drug was well tolerated by patients without eliciting serious side effects. A Phase II clinical trial Excellairâ„¢ has been initiated in 2009; the results are not yet available during the preparation of this review [199, 200] .

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