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Drug-tunable multidimensional synthetic gene control using inducible degron-tagged dCas9 effectors

Author

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  • Dirk A. Kleinjan

    (Biochemistry, and Biotechnology, SynthSys, School of Biological Sciences, University of Edinburgh)

  • Caroline Wardrope

    (Biochemistry, and Biotechnology, SynthSys, School of Biological Sciences, University of Edinburgh)

  • Si Nga Sou

    (Biochemistry, and Biotechnology, SynthSys, School of Biological Sciences, University of Edinburgh)

  • Susan J. Rosser

    (Biochemistry, and Biotechnology, SynthSys, School of Biological Sciences, University of Edinburgh
    University of Edinburgh)

Abstract

The nuclease-deactivated variant of CRISPR-Cas9 proteins (dCas9) fused to heterologous transactivation domains can act as a potent guide RNA sequence-directed inducer or repressor of gene expression in mammalian cells. In such a system the long-term presence of a stable dCas9 effector can be a draw-back precluding the ability to switch rapidly between repressed and activated target gene expression states, imposing a static environment on the synthetic regulatory circuits in the cell. To address this issue we have generated a toolkit of conditionally degradable or stabilisable orthologous dCas9 or Cpf1 effector proteins, thus opening options for multidimensional control of functional activities through combinations of orthogonal, drug-tunable artificial transcription factors.

Suggested Citation

  • Dirk A. Kleinjan & Caroline Wardrope & Si Nga Sou & Susan J. Rosser, 2017. "Drug-tunable multidimensional synthetic gene control using inducible degron-tagged dCas9 effectors," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01222-y
    DOI: 10.1038/s41467-017-01222-y
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    Cited by:

    1. Gemma Noviello & Rutger A. F. Gjaltema & Edda G. Schulz, 2023. "CasTuner is a degron and CRISPR/Cas-based toolkit for analog tuning of endogenous gene expression," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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