Röhl Thomas, Kurreck Jens
Institute of Chemistry and Biochemistry, Free University Berlin, Germany.
J Neurochem. 2006 Oct;99(2):371-80. doi: 10.1111/j.1471-4159.2006.04082.x.
Within the course of only the last few years, RNA interference (RNAi) has been established as a standard technology for investigation of protein function and target validation. The present review summarizes recent progress made in the application of RNAi in neurosciences with special emphasis on pain research. RNAi is a straightforward method to generate loss-of-function phenotypes for any gene of interest. In mammals, silencing is induced by small interfering RNAs (siRNAs), which have been shown to surpass traditional antisense molecules. Due to its high specificity, RNAi has the potential for subtype selective silencing of even closely related genes. One of the major challenges for in vivo investigations of RNAi remains efficient delivery of siRNA molecules to the relevant tissues and cells, particularly to the central nervous system. Various examples will be given to demonstrate that intrathecal application of siRNAs is a suitable approach to analyse the function of receptors or other proteins that are hypothesized to play an important role in pain signalling. Intensive efforts are currently ongoing to solve remaining problems such as the risk of off-target effects, the stability of siRNA molecules and their efficient delivery to the CNS. RNAi has thus demonstrated that it is an extremely valuable tool for the development of new analgesic drugs.
在仅仅过去几年的时间里，RNA干扰（RNAi）已成为用于研究蛋白质功能和靶点验证的标准技术。本综述总结了RNAi在神经科学应用中的最新进展，特别着重于疼痛研究。RNAi是一种为任何感兴趣的基因产生功能缺失表型的直接方法。在哺乳动物中，小干扰RNA（siRNA）可诱导基因沉默，已证明其优于传统的反义分子。由于其高特异性，RNAi甚至有可能对密切相关的基因进行亚型选择性沉默。RNAi体内研究的主要挑战之一仍然是将siRNA分子有效递送至相关组织和细胞，特别是中枢神经系统。将给出各种实例以证明鞘内应用siRNA是一种分析假定在疼痛信号传导中起重要作用的受体或其他蛋白质功能的合适方法。目前正在进行大量努力以解决诸如脱靶效应风险、siRNA分子稳定性及其向中枢神经系统的有效递送等遗留问题。因此，RNAi已证明它是开发新型镇痛药的极其有价值的工具。
