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Engineering polydactyl zinc-finger transcription factors

Nature Biotechnology volume 20, pages 135–141 (2002)Cite this article

Abstract

The availability of rapid and robust methods for controlling gene function is of prime importance not only for assigning functions to newly discovered genes, but also for therapeutic intervention. Traditionally, gene function has been probed by often-laborious methods that either increase the level of a gene product or decrease it. Advances now make it possible to rapidly produce zinc-finger proteins capable of recognizing virtually any 18 bp stretch of DNA—a sequence long enough to specify a unique address in any genome. The attachment of functional domains also allows the design of tailor-made transcription factors for specific genes. Recent studies demonstrate that artificial transcription factors are capable of controlling the expression of endogenous genes in their native chromosomal context with a high degree of specificity in both animals and plants. Dominant regulatory control of expression of any endogenous gene can be achieved rapidly and can be also placed under chemical control. A wide range of potential applications is now within reach.

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Figure 1: Zinc-finger–based DNA recognition and modification devices.
Figure 2: Strategies for the production of ZFPs with desired DNA-binding specificity.
Figure 3: Structure of a 1,400 bp human erbB-2 promoter fragment.

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  1. Roger R. Beerli

    Present address: Cytos Biotechnology AG, Wagistrasse 21, 8952, Zurich-Schlieren, Switzerland

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  1. The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, La Jolla, 92037, CA

    Roger R. Beerli & Carlos F. Barbas III

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  2. Carlos F. Barbas III
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Correspondence to Carlos F. Barbas III.

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Beerli, R., Barbas, C. Engineering polydactyl zinc-finger transcription factors. Nat Biotechnol 20, 135–141 (2002). https://doi.org/10.1038/nbt0202-135

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