Pulmonary delivery of siRNA as a novel treatment for lung diseases

摘要

The lung offers various beneficial characteristics as a target organ for therapeutic approaches. Beside the large (hundreds of square meters) and very well perfused (5 l/min) surface area, extremely thin epithelium (0.1-0.2 mum) and high blood volume in pulmonary capillaries (0.25 l), it also captivates with a relatively low enzyme activity and slow surface clearance [1]. Owing to its location and function, the pulmonary region is susceptible to a number of specific diseases, being directly accessible to harmful substances. Lung-related disorders therefore contribute substantially to the global disease burden in regards to public health and economic resources. For a considerable number of those pathologies including asthma, idiopathic pulmonary fibrosis, respiratory syncytial virus and, moreover, lung cancer as the leading cause of cancer death worldwide, the underlying cause is elevated transcription of certain genes [2,3]. Therefore, the interference with gene expression via RNA interference in principle offers great potential to help address unmet.medical needs in this regard.