Abstract
RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside.
Highlights
Lung diseases are among the leading causes of death worldwide
Mycobacterium tuberculosis which is the causative agent of tuberculosis that typically reside in the alveolar macrophages [49], otherwise the RNA interference (RNAi) molecules are subjected to degradation inside the macrophages before reaching their target sites
The group treated with ALN-RSV01 had a significantly lower number of respiratory syncytial virus (RSV) infection compared to the placebo group [140]
Summary
Lung diseases are among the leading causes of death worldwide. Current treatment of lung diseases such as lung cancer [1], respiratory infections [2,3], inflammatory diseases [4,5] and pulmonary fibrosis [6] have limited efficacy. The therapeutic potential of RNAi was soon realized It presents a new and powerful approach to treat or prevent many diseases including respiratory disorders by modulating gene expression [8,9,10,11,12,13]. RNAi can be mediated by various types of RNA molecules, including long dsRNA, short interfering RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA). Interfering RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA). Gene silencing effect dependent upon fully complementary binding of the target messenger (mRNA). MicroRNA is dependent upon fully complementary binding of the target messenger RNA (mRNA). Mediates gene silencing via the partial complementary synthesized (miRNA mimic). MiRNA mediates gene silencing via the partial complementarybinding binding the target mRNAs
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