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Multistable and dynamic CRISPRi-based synthetic circuits

Author

Listed:
  • Javier Santos-Moreno

    (University of Lausanne)

  • Eve Tasiudi

    (ETH Zurich and SIB Swiss Institute of Bioinformatics)

  • Joerg Stelling

    (ETH Zurich and SIB Swiss Institute of Bioinformatics)

  • Yolanda Schaerli

    (University of Lausanne)

Abstract

Gene expression control based on CRISPRi (clustered regularly interspaced short palindromic repeats interference) has emerged as a powerful tool for creating synthetic gene circuits, both in prokaryotes and in eukaryotes; yet, its lack of cooperativity has been pointed out as a potential obstacle for dynamic or multistable synthetic circuit construction. Here we use CRISPRi to build a synthetic oscillator (“CRISPRlator”), bistable network (toggle switch) and stripe pattern-forming incoherent feed-forward loop (IFFL). Our circuit designs, conceived to feature high predictability and orthogonality, as well as low metabolic burden and context-dependency, allow us to achieve robust circuit behaviors in Escherichia coli populations. Mathematical modeling suggests that unspecific binding in CRISPRi is essential to establish multistability. Our work demonstrates the wide applicability of CRISPRi in synthetic circuits and paves the way for future efforts towards engineering more complex synthetic networks, boosted by the advantages of CRISPR technology.

Suggested Citation

  • Javier Santos-Moreno & Eve Tasiudi & Joerg Stelling & Yolanda Schaerli, 2020. "Multistable and dynamic CRISPRi-based synthetic circuits," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16574-1
    DOI: 10.1038/s41467-020-16574-1
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    Cited by:

    1. Javier Santos-Moreno & Eve Tasiudi & Hadiastri Kusumawardhani & Joerg Stelling & Yolanda Schaerli, 2023. "Robustness and innovation in synthetic genotype networks," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Ankush Auradkar & Annabel Guichard & Saluja Kaduwal & Marketta Sneider & Ethan Bier, 2023. "tgCRISPRi: efficient gene knock-down using truncated gRNAs and catalytically active Cas9," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Yuanli Gao & Lei Wang & Baojun Wang, 2023. "Customizing cellular signal processing by synthetic multi-level regulatory circuits," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. William M. Shaw & Lucie Studená & Kyler Roy & Piotr Hapeta & Nicholas S. McCarty & Alicia E. Graham & Tom Ellis & Rodrigo Ledesma-Amaro, 2022. "Inducible expression of large gRNA arrays for multiplexed CRISPRai applications," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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