Effective prevention and therapy of experimental allergic asthma using a GATA-3-specific DNAzyme.

摘要: Background Allergic bronchial asthma is a chronic inflammatory disease of the airways. The transcription factor GATA-3 was shown to play an important role in T H 2 cell activation, but also regulation other types involved including mast cells, eosinophils, and epithelial cells. DNAzymes represent new class antisense molecules that combines specificity DNA base pairing with inherent RNA-cleaving enzymatic activity. Objective To develop mRNA-specific DNAzyme analyze its allergy-preventing activity murine models experimental allergic asthma. Methods most active (termed gd21 ) selected by vitro cleavage assays. airway inflammation assessed cytokine analysis within bronchoalveolar lavage. Lung histology, goblet hyperplasia lung function, analyzed using head-out body-plethysmography. Results Intranasal administration prevented mucus production inhibited development hyperresponsiveness methacholine acute inflammation. Similar effects were detected model Interestingly, at least as effective molecules, off-target not detected. Further experiments indicated pulmonary surfactant may facilitate cellular uptake acting endogenous transfectant. Conclusion These results indicate topical application GATA-3–specific promising novel approach for treatment