Kourtidis A, Eifert C, Conklin D S
Department of Biomedical Sciences, Gen"NY"Sis Center for Excellence Cancer Genomics, University at Albany, Rensselaer, NY 12144, USA.
Ernst Schering Res Found Workshop. 2007(61):1-21. doi: 10.1007/978-3-540-31339-7_1.
The emergence of systems biology is certain to transform the identification and validation of therapeutic targets in modern drug discovery. A relatively recent systems biology approach is functional genomics, which identifies the molecular mechanisms responsible for a specific phenotype by interrogating the activity of all of an organism's genes. Initially undertaken in model organisms such as Caenorhabditis elegans, Saccharomyces cerevisiae, and Drosophila melanogaster, functional genomics has now moved into the realm of mammalian cells both in vitro and in vivo due to the development of RNA interference. RNA interference is a conserved biological process that has evolved to specifically and efficiently silence genes. Genome-wide screens using RNA interference have proven powerful in elucidating components of functionally related pathways and have therefore become integral for the development of new and improved therapeutic targets. This article provides an overview of many of the systems biology approaches taken, using RNA interference, in order to demonstrate how it may be used today for drug discovery and tomorrow as a targeted therapy.
系统生物学的出现必将改变现代药物研发中治疗靶点的识别与验证。一种相对较新的系统生物学方法是功能基因组学，它通过研究生物体所有基因的活性来确定导致特定表型的分子机制。功能基因组学最初是在秀丽隐杆线虫、酿酒酵母和黑腹果蝇等模式生物中进行的，由于RNA干扰技术的发展，现在已进入哺乳动物细胞的体外和体内研究领域。RNA干扰是一种保守的生物学过程，其进化目的是特异性且高效地使基因沉默。利用RNA干扰进行全基因组筛选已被证明在阐明功能相关通路的组成成分方面非常强大，因此已成为开发新的和改进的治疗靶点不可或缺的手段。本文概述了许多采用RNA干扰的系统生物学方法，以展示其如今如何用于药物研发以及未来如何作为一种靶向治疗方法。
