Sera Takashi
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
Adv Drug Deliv Rev. 2009 Jul 2;61(7-8):513-26. doi: 10.1016/j.addr.2009.03.012. Epub 2009 Apr 23.
Artificial transcription factors (ATFs) are potentially a powerful molecular tool to modulate endogenous target gene expression in living cells and organisms. To date, many DNA-binding molecules have been developed as the DNA-binding domains for ATFs. Among them, ATFs comprising Cys(2)His(2)-type zinc-finger proteins (ZFPs) as the DNA-binding domain have been extensively explored. The zinc-finger-based ATFs specifically recognize targeting sites in chromosomes and effectively up- and downregulate expression of their target genes not only in vitro, but also in vivo. In this review, after briefly introducing Cys(2)His(2)-type ZFPs, I will review the studies of endogenous human gene regulation by zinc-finger-based ATFs and other applications as well.
人工转录因子(ATFs)可能是一种强大的分子工具,可用于调节活细胞和生物体中的内源性靶基因表达。迄今为止,许多DNA结合分子已被开发用作ATFs的DNA结合结构域。其中,包含Cys(2)His(2)型锌指蛋白(ZFPs)作为DNA结合结构域的ATFs已得到广泛研究。基于锌指的ATFs能够特异性识别染色体上的靶向位点,不仅在体外,而且在体内都能有效上调和下调其靶基因的表达。在这篇综述中,在简要介绍Cys(2)His(2)型ZFPs之后,我还将综述基于锌指的ATFs对人类内源性基因调控的研究以及其他应用。