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

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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.