Gommans Willemijn M, Haisma Hidde J, Rots Marianne G
Department of Therapeutic Gene Modulation, University of Groningen, The Netherlands.
J Mol Biol. 2005 Dec 2;354(3):507-19. doi: 10.1016/j.jmb.2005.06.082. Epub 2005 Oct 5.
Modulating gene expression directly at the DNA level represents a novel approach to control cellular processes. In this respect, zinc finger protein DNA-binding domains can be engineered to target virtually any gene. Coupling of a transcription activation or repression domain to these zinc fingers permits regulating gene expression at will, providing a platform of unlimited therapeutic applications. In this review, steps involved in the engineering of zinc finger protein transcription factors are described. In addition, an overview of endogenous genes successfully targeted for modulating expression by engineered zinc finger protein transcription factors is given. So far, research has mainly focused on targeting genes involved in cancer and angiogenesis, with encouraging evaluation in vivo and progression into a clinical trial. Altogether, engineered zinc finger proteins offer a new and exciting direction in the field of medical research with promising prospects.
直接在DNA水平上调节基因表达代表了一种控制细胞过程的新方法。在这方面，可以设计锌指蛋白DNA结合结构域以靶向几乎任何基因。将转录激活或抑制结构域与这些锌指偶联可随意调节基因表达，提供了一个具有无限治疗应用的平台。在这篇综述中，描述了锌指蛋白转录因子工程化所涉及的步骤。此外，还概述了通过工程化锌指蛋白转录因子成功靶向调节表达的内源基因。到目前为止，研究主要集中在靶向参与癌症和血管生成的基因，在体内评估令人鼓舞并已进入临床试验阶段。总之，工程化锌指蛋白在医学研究领域提供了一个新的、令人兴奋的方向，前景广阔。
