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Creation of New Functional Artificial Metallofingers : Construction of Library and Development to Gene Regulation

新型功能性人工金属手指的创建：库的构建和基因调控的发展

基本信息

批准号：
17390028
负责人：
SUGIURA Yukio
金额：
$ 10.16万
依托单位：
Doshisha Women's College of Liberal Arts
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

The design of DNA-binding proteins for the specific control of the gene expression is one of big challenges for several research laboratories in the post-genomic era. An artificial transcription factor with the desired DNA binding specificity could work as a powerful tool and drug to regulate the target gene. the zinc-finger proteins, which typically contain many fingers linked in a tandem fashion, are some of the most intensively studied DNA-binding proteins. In particular, the Cys_2His_2-type zinc finger is one of most common DNA-binding motifs in eukaryotes. A simple mode of DNA recognition by the Cys_2His_2-type zinc-finger domain provides an ideal framework for designing proteins with new function. Our laboratory has utilized several design strategies to create new zinc-finger peptides/proteins by redesigning the Cys_2His_2-type zinc-finger motif. This research focuses on the aspects of design strategies, mainly from our recent results, for the creation of artificial zinc-finger proteins, and discusses the possible application of zinc-finger technology for gene regulation and gene therapy. In particular, the zinc-finger technology toward desired endogenous gene regulation is quickly progressing and its application to medical treatment has definitely been realized. These demonstration suggest that designer zinc-finger proteins have great potential for applications in biomedicine and biotechnology. In the near future, as zinc-finger research advances, it may become possible to construct complicated synthetic cell network and control better higher level vital functions at will.

设计特异性调控基因表达的DNA结合蛋白是后基因组时代许多研究实验室面临的重大挑战之一。具有所需DNA结合特异性的人工转录因子可以作为调控靶基因的有力工具和药物。锌指蛋白通常包含许多以串联方式连接的指，是研究最深入的DNA结合蛋白。Cys_2His_2型锌指是真核生物中最常见的DNA结合基序之一。Cys_2His_2型锌指结构域识别DNA的简单模式为设计具有新功能的蛋白质提供了理想的框架。我们的实验室已经利用了几种设计策略，通过重新设计Cys_2His_2型锌指基序来创建新的锌指肽/蛋白。本研究主要从锌指蛋白的设计策略等方面，探讨了锌指蛋白在基因调控和基因治疗中的应用前景。特别是针对内源性基因调控的锌指技术正在快速发展，其在医学治疗中的应用已经明确实现。这些结果表明，设计的锌指蛋白在生物医学和生物技术中具有巨大的应用潜力。在不久的将来，随着锌指研究的进展，有可能构建复杂的合成细胞网络，并更好地控制更高层次的生命功能。