Rychahou Piotr G, Evers B Mark
Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA.
Methods Mol Biol. 2010;623:189-95. doi: 10.1007/978-1-60761-588-0_12.
RNA interference (RNAi) holds considerable promise as a novel therapeutic strategy to silence disease-causing genes not amenable to conventional therapeutics. Since it relies on small interfering RNAs (siRNAs), which are the mediators of RNAi-induced specific mRNA degradation, a major issue is the delivery of therapeutically active siRNAs into the target tissue. In vivo gene silencing with RNAi has been reported using both viral vector delivery and high-pressure, high-volume intravenous (i.v.) injection of synthetic siRNAs. For safety reasons, strategies based on viral vector delivery may be only of limited clinical use. The more desirable approach is to directly deliver active siRNAs. We describe the use of hydrodynamic administration as a technique to deliver naked siRNA constructs into experimental animals as a method of transient gene knockdown. This approach demonstrates that RNAi can be used to silence endogenous genes, involved in the cause of human diseases, with a clinically acceptable formulation and route of administration.
RNA干扰（RNAi）作为一种新型治疗策略，有望沉默那些传统疗法难以对付的致病基因，具有巨大潜力。由于它依赖于小干扰RNA（siRNAs），而小干扰RNA是RNAi诱导特异性mRNA降解的介质，一个主要问题是将具有治疗活性的小干扰RNA递送至靶组织。已有报道称，使用病毒载体递送以及高压、大容量静脉注射合成小干扰RNA均可在体内实现RNAi介导的基因沉默。出于安全考虑，基于病毒载体递送的策略在临床上的应用可能有限。更理想的方法是直接递送活性小干扰RNA。我们描述了利用流体动力学给药技术，将裸露的小干扰RNA构建体递送至实验动物体内，作为一种瞬时基因敲低的方法。该方法表明，RNAi可通过临床可接受的制剂和给药途径，用于沉默与人类疾病病因相关的内源性基因。
