Fujita Yu, Kuwano Kazuyoshi, Ochiya Takahiro
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan.
Int J Mol Sci. 2015 Mar 6;16(3):5254-70. doi: 10.3390/ijms16035254.
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.
RNA干扰(RNAi)已成为研究靶点识别的有力工具,并有望用于治疗性基因沉默的开发。RNAi递送和靶点选择方面的最新进展为转化医学研究提供了显著机遇。RNAi的诱导依赖于小干扰RNA,其影响特定信使核糖核酸(mRNA)的降解。两种类型的小RNA分子,即小干扰RNA(siRNA)和微小RNA(miRNA),在RNAi技术中发挥着核心作用。基于RNAi的治疗性递送的成功可能取决于找到一种递送途径、先进的递送载体以及核酸修饰。肺癌仍然是全球癌症死亡的主要原因,因此迫切需要新的治疗策略。最近,我们报道了一种新型平台(PnkRNA™和nkRNA®),可在肺癌异种移植模型中通过吸入促进无递送载体的裸RNAi方法。我们认为,一类新型的RNAi治疗剂和局部给药系统也可为基于RNAi的癌症治疗临床应用策略带来希望。在本文中,我们展示了RNAi递送系统的最新策略,并提出了基于RNAi的疗法在肺癌治疗中的潜在临床应用价值。