Recent developments in the engineering of zinc finger proteins

Abstract

Abstract Within the last 20 years, the understanding of the biology of the ‘classical’ or Cys2His2 zinc finger domain has progressed rapidly from the initial identification of the zinc finger as a repetitive zinc-binding motif in transcription factors to its use in biotechnology. The domain is the most abundant DNA-binding motif in the human genome and is a component of many key eukaryotic transcription factors involved in growth and development. Numerous structures now exist for this domain and its mode of action is known in a variety of zinc finger–DNA complexes. Application of this knowledge has led to the development of ‘designer’ transcription factors where zinc fingers have been engineered to bind desired DNA sequences. Recently, advances have been made in this field that potentially allow the targeting of any DNA site. Consideration of chromatin structure and the use of effector domains in these ‘designer’ transcription factors have made possible the regulation of a number of endogenous genes. These advances in the customised regulation of genes will be discussed in detail, as well as the potential to use these proteins in functional genomics and gene therapy applications.