Pulmonary siRNA delivery for lung disease: Review of recent progress and challenges

Lung diseases are a leading cause of mortality worldwide and there exists urgent need for new therapies. Approval of the first siRNA treatments in humans has opened the door for further exploration of this therapeutic strategy for other disease states. Pulmonary delivery of siRNA-based biopharmaceuticals offers the potential to address multiple unmet medical needs in lung-related diseases because of the specific physiology of the lung and characteristic properties of siRNA. Inhalation-based siRNA delivery designed for efficient, targeted delivery to specific cells within the lung holds great promise. Efficient delivery of siRNA directly to the lung, however, is relatively complex. This review focuses on the barriers that impact pulmonary siRNA delivery and successful recent approaches to advance this field forward. We focus on the pulmonary barriers that affect siRNA delivery, the disease-dependent pathological changes and their role in pulmonary disease and impact on siRNA delivery, as well as the recent development on the pulmonary siRNA delivery systems.