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Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors

Gene Therapy volume 10, pages 513–522 (2003)Cite this article

Abstract

Epigenetic control of transcription is essential for mammalian development and its deregulation causes human disease. For example, loss of proper imprinting control at the IGF2–H19 domain is a hallmark of cancer and Beckwith–Wiedemann syndrome, with no targeted therapeutic approaches available. To address this deficiency, we engineered zinc-finger transcription proteins (ZFPs) that specifically activate or repress the IGF2 and H19 genes in a domain-dependent manner. Importantly, we used these ZFPs successfully to reactivate the transcriptionally silent IGF2 and H19 alleles, thus overriding the natural mechanism of imprinting and validating an entirely novel avenue for ‘transcription therapy’ of human disease.

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Author notes

  1. A P Wolffe: Deceased.

Authors and Affiliations

  1. Sangamo BioSciences, Inc., Point Richmond Tech Center, Richmond, CA, USA

    Y Jouvenot, L Zhang, P-Q Liu & P D Gregory

  2. Department of Development and Genetics, Evolution Biology Centre, Uppsala University, Uppsala, Sweden

    V Ginjala & Rolf Ohlsson

  3. Division of Molecular and Cellular Genetics, Faculty of Medicine, Tottori University, Tottori, Japan

    M Oshimura

  4. Institute of Genetic Medicine, Johns Hopkins University School of Medicine, MA, USA

    A P Feinberg

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  1. Y Jouvenot
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Jouvenot, Y., Ginjala, V., Zhang, L. et al. Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors. Gene Ther 10, 513–522 (2003). https://doi.org/10.1038/sj.gt.3301930

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  • DOI: https://doi.org/10.1038/sj.gt.3301930

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