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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.

设计用于特异性控制基因表达的DNA结合蛋白是后基因组时代一些研究实验室面临的巨大挑战之一。具有所需 DNA 结合特异性的人工转录因子可以作为调节靶基因的强大工具和药物。锌指蛋白通常包含许多以串联方式连接的指状蛋白，是研究最深入的 DNA 结合蛋白之一。特别是，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型锌指结构域的DNA识别简单模式为设计具有新功能的蛋白质提供了理想的框架。我们的实验室利用多种设计策略，通过重新设计Cys_2His_2型锌指基序来创造新的锌指肽/蛋白质。本研究重点关注设计策略方面，主要来自我们最近的研究成果，用于创建人工锌指蛋白，并讨论了锌指技术在基因调控和基因治疗中的可能应用。特别是针对所需内源基因调控的锌指技术正在迅速进展，其在医学治疗中的应用已经明确实现。这些演示表明，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，构建复杂的合成细胞网络并随意控制更好的高级生命功能可能成为可能。