Abstract
RNA interference (RNAi) is rapidly becoming an important method for analyzing gene functions in many eukaryotes and holds promise for the development of therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are central to RNAi. Drug discovery studies and novel treatments of siRNAs are currently targeting a wide range of diseases, including various viral infections and cancers. Lung diseases in general are attractive targets for siRNA therapeutics because of their lethality and prevalence. In addition, the lung is anatomically accessible to therapeutic agents via the intrapulmonary route. Recently, increasing evidence indicates that miRNAs play an important role in lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are being targeted for therapeutic purposes. In this review, we present strategies for RNAi delivery and discuss the current state-of-the-art RNAi-based therapeutics for various lung diseases.
Highlights
RNA interference (RNAi) is a natural endogenous mechanism for silencing gene expression that, recently, has been the focus of considerable attention for its potential use in new drugs [1]
This review focuses on the latest development of pulmonary delivery and future plans for the RNAi-based treatment of various lung diseases
The advancement of pulmonary small interfering RNAs (siRNAs) delivery to the clinic illustrates that RNAi-based therapy holds a central place in the future treatment of lung diseases
Summary
RNA interference (RNAi) is a natural endogenous mechanism for silencing gene expression that, recently, has been the focus of considerable attention for its potential use in new drugs [1]. RNAi-based therapeutics are promptly degraded by nucleases when they are administered systemically, and chemical modifications at specific positions or formulation with delivery vectors have been shown to improve stability, but they may attenuate the suppressive activity of oligonucleotides [6]. Their systemic administration may induce undesirable off-target effects by activating the innate immune system via toll-like receptor (TLR)-dependent or independent mechanisms, leading to an increased number of inflammatory cytokines [7]. This review focuses on the latest development of pulmonary delivery and future plans for the RNAi-based treatment of various lung diseases
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