Abstract
RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications. Lung cancer is still the leading cause of cancer death worldwide, for which novel therapeutic strategies are critically needed. Recently, we have reported a novel platform (PnkRNA™ and nkRNA®) to promote naked RNAi approaches through inhalation without delivery vehicles in lung cancer xenograft models. We suggest that a new class of RNAi therapeutic agent and local drug delivery system could also offer a promising RNAi-based strategy for clinical applications in cancer therapy. In this article, we show recent strategies for an RNAi delivery system and suggest the possible clinical usefulness of RNAi-based therapeutics for lung cancer treatment.
Highlights
RNA interference (RNAi) is one of the most exciting discoveries in molecular biology and represents a significant breakthrough in our understanding of the function and regulation of genes in cells [1]
The silencing technology to suppress the expression of various genes by using different molecules, such as small interfering RNA, short hairpin RNA, and microRNA, is applicable to many kinds of therapeutics for human diseases caused by specific genes
The success of an RNAi-based therapy in clinical trials rests on careful selection of target genes and miRNAs
Summary
RNA interference (RNAi) is one of the most exciting discoveries in molecular biology and represents a significant breakthrough in our understanding of the function and regulation of genes in cells [1]. The silencing technology to suppress the expression of various genes by using different molecules, such as small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA), is applicable to many kinds of therapeutics for human diseases caused by specific genes. They are all commonly cleaved by an endogenous enzyme called Dicer that gives rise to the important transcription factors involved in the gene expression regulation. The systemic delivery may induce adverse events, such as aggregation and complement activation, liver toxicity and stimulation of the immune response [19] For these reasons, we consider that local administration of RNAi-based therapeutics to the target cancer cells may be a promising approach to overcome the problems of systemic administration. We offer perspectives on future applications of siRNA and miRNA therapeutics and discuss the promise and limitations of delivery strategies for lung cancer
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