Discov Med. 2003 Dec;3(19):32-5.
Discovery medicine
Stacey A Thibodeau, J Keith Joung
PMID: 20705034
Extract: The Cys2His2 zinc finger domain (hereafter simply "zinc finger") provides a useful scaffold for creating customized DNA-binding proteins, a technology with potential applications in biological research, molecular medicine, and gene therapy. Using a combination of targeted randomization and selection methodologies (e.g., phage display), many research groups have successfully altered the DNA-binding specificities of single zinc fingers, which typically recognize three to four base pairs of DNA. In these experiments, potential DNA-binding residues in a finger's a-helix (or "recognition helix") were randomized to generate a library of variants and then selection methods were used to identify fingers with desired DNA-binding specificities. To create synthetic multi-finger proteins capable of recognizing longer DNA sequences, various investigators have linked together three or more pre-selected or pre-characterized finger domains. This type of strategy, which assumes that individual fingers behave in a modular fashion, permits the rapid assembly of multi-finger proteins directed to bind a wide variety of different DNA sequences.
