Zinc finger proteins as designer transcription factors

Recent progress in the design and selection of novel zinc finger proteins with desired DNA binding specificities now allows construction of tailor-made DNA-binding proteins that specifically recognize almost any predetermined DNA sequence. Such novel or "designer" zinc finger proteins with desired DNA binding specificities can serve as efficient transcription factors in various mammalian cell Lines. In addition, they may be broadly useful in the regulation of endogenous genes in transgenic organisms and eventually in gene therapy applications. In this report, we use a series of transient and stable transfection experiments to demonstrate that the expression of a target gene can be controlled by changing the in vivo concentration of designer zinc finger proteins in a dose-dependent manner. We also report that designer zinc finger proteins can access their binding sites integrated into the genome and function as potent transcription factors. Our results suggest that designer zinc finger transcription factors that specifically recognize appropriate sites in the promoter of a target gene may have broad applications in the post-genomic era.