Abstract

Zinc-finger nucleases (ZFNs) are emerging as very powerful tools for directed genome modifications. Their key features are: a DNA-binding domain comprised of zinc fingers that can be designed to favor very specific targets; a nonspecific cleavage domain that must dimerize to cut DNA - this requirement enhances specificity and minimizes random cleavage. ZFNs have been shown to be effective in a wide range of organisms and cell types. This article reviews discoveries that led to the development of ZFNs, cites examples of successes in genome engineering, and projects how ZFNs may be used in the future, particularly in applications to humans.

Keywords: DNA repair, gene targeting, homologous recombination, nonhomologous end joining (NHEJ), zinc-finger nuclease (ZFN), zinc fingers, Zinc-finger nucleases, genome engineering, Cys2His2, double-strand break, polymerase chain reaction, protein-protein interactions, multi-finger proteins, plasmid DNA, oligonucleotide, Xenopus oocyte system, agrobacterial transformation, Drosophila: polymorphisms