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Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs

Author

Listed:
  • Kale Kundert

    (University of California San Francisco)

  • James E. Lucas

    (University of California San Francisco)

  • Kyle E. Watters

    (University of California Berkeley)

  • Christof Fellmann

    (University of California Berkeley)

  • Andrew H. Ng

    (University of California San Francisco)

  • Benjamin M. Heineike

    (University of California San Francisco)

  • Christina M. Fitzsimmons

    (University of California San Francisco
    National Institutes of Health)

  • Benjamin L. Oakes

    (University of California Berkeley)

  • Jiuxin Qu

    (University of California San Francisco)

  • Neha Prasad

    (University of California San Francisco)

  • Oren S. Rosenberg

    (University of California San Francisco
    Chan Zuckerberg Biohub)

  • David F. Savage

    (University of California Berkeley)

  • Hana El-Samad

    (Chan Zuckerberg Biohub
    University of California San Francisco)

  • Jennifer A. Doudna

    (University of California Berkeley
    University of California Berkeley)

  • Tanja Kortemme

    (Chan Zuckerberg Biohub
    University of California San Francisco)

Abstract

The CRISPR-Cas9 system provides the ability to edit, repress, activate, or mark any gene (or DNA element) by pairing of a programmable single guide RNA (sgRNA) with a complementary sequence on the DNA target. Here we present a new method for small-molecule control of CRISPR-Cas9 function through insertion of RNA aptamers into the sgRNA. We show that CRISPR-Cas9-based gene repression (CRISPRi) can be either activated or deactivated in a dose-dependent fashion over a >10-fold dynamic range in response to two different small-molecule ligands. Since our system acts directly on each target-specific sgRNA, it enables new applications that require differential and opposing temporal control of multiple genes.

Suggested Citation

  • Kale Kundert & James E. Lucas & Kyle E. Watters & Christof Fellmann & Andrew H. Ng & Benjamin M. Heineike & Christina M. Fitzsimmons & Benjamin L. Oakes & Jiuxin Qu & Neha Prasad & Oren S. Rosenberg &, 2019. "Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09985-2
    DOI: 10.1038/s41467-019-09985-2
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    Cited by:

    1. Gregory W. Goldberg & Manjunatha Kogenaru & Sarah Keegan & Max A. B. Haase & Larisa Kagermazova & Mauricio A. Arias & Kenenna Onyebeke & Samantha Adams & Daniel K. Beyer & David Fenyö & Marcus B. Noye, 2024. "Engineered transcription-associated Cas9 targeting in eukaryotic cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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