Engineering zinc finger protein transcription factors: The therapeutic relevance of switching endogenous gene expression on or off at command

Modulating gene expression directly at the DNA level represents a novel approach to control cellular processes. In this respect, zinc finger protein DNA-binding domains can be engineered to target virtually any gene. Coupling of a transcription activation or repression domain to these zinc fingers permits regulating gene expression at will, providing a platform of unlimited therapeutic applications. In this review, steps involved in the engineering of zinc finger protein transcription factors are described. In addition, an overview of endogenous genes successfully targeted for modulating expression by engineered zinc finger protein transcription factors is given. So far, research has mainly focused on targeting genes involved in cancer and angiogenesis, with encouraging evaluation in vivo and progression into a clinical trial. Altogether, engineered zinc finger proteins offer a new and exciting direction in the field of medical research with promising prospects. (c) 2005 Elsevier Ltd. All rights reserved.