Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside

Qiu, Yingshan; Lam, Jenny K. W.; Leung, Susan W. S.; Liang, Wanling

Asthma is characterized by the variable and reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus hypersecretion and chronic inflammation [176] . The most common form of asthma is allergic asthma, which is triggered by environmental stimuli such as house dust and seasonal pollen [177] . According to WHO, it is estimated that around 334 million peoples have asthma worldwide [178] . The mainstay treatments of asthma are corticosteroids, β 2 -adrenergic receptor agonists and leukotriene receptor antagonists, either alone or in combination. Although these medications can manage the conditions in most of the patients, there are still challenges of poor patient compliance, intolerability and long term adverse effects [179] . For persistent allergic asthmatic patients, omalizumab which is an anti-immunoglobulin E (IgE) monoclonal antibody can be used, but the high cost and parenteral administration make it less favorable [180] . Alternative anti-inflammatory drugs are needed. Many inflammatory mediators are identified to be involved in the pathogenesis of asthma and they are investigated as potential targets of RNAi therapy. These include cytokines/chemokines [181] , transcription factors [168] , tyrosine kinases/tyrosine kinase receptors [172] and co-stimulatory molecules [182] .