Zinc finger proteins as designer transcription factors

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