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J Biol Chem, Vol. 275, Issue 12, 8742-8748, March 24, 2000
and
§¶
From the Recent progress in the design and selection of
novel zinc finger proteins with desired DNA binding specificities now
allows construction of tailor-made DNA-binding proteins that
specifically recognize almost any predetermined DNA sequence. Such
novel or "designer" zinc finger proteins with desired DNA binding
specificities can serve as efficient transcription factors in various
mammalian cell lines. In addition, they may be broadly useful in the
regulation of endogenous genes in transgenic organisms and eventually
in gene therapy applications. In this report, we use a series of transient and stable transfection experiments to demonstrate that the
expression of a target gene can be controlled by changing the in
vivo concentration of designer zinc finger proteins in a
dose-dependent manner. We also report that designer zinc
finger proteins can access their binding sites integrated into the
genome and function as potent transcription factors. Our results
suggest that designer zinc finger transcription factors that
specifically recognize appropriate sites in the promoter of a target
gene may have broad applications in the post-genomic era.
Samsung Biomedical Research Institute and
§ Toolgen Incorporation, Sungkyunkwan University School of
Medicine, 300 Chunchun-Dong, Changan-Ku,
Suwon, Republic of Korea
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