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Modeling Dynamic Transcriptional Circuits with CRISPRi

Clamons, Samuel E. and Murray, Richard M. (2017) Modeling Dynamic Transcriptional Circuits with CRISPRi. . (Unpublished) http://resolver.caltech.edu/CaltechAUTHORS:20181031-100007899

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Abstract

Targeted transcriptional repression with catalytically inactive Cas9 (CRISPRi) can be used to build gene regulatory nets similar in principle to those made with traditional transcription factors, and promises to do so with better orthogonality, programmability, and extensibility. We use a simple dynamical model of CRISPRi to understand its behavior and requirements, and to show that CRISPRi can recapitulate several classic gene regulatory circuits, including the repressilator, a toggle switch, and an incoherent feed-forward loop pulse generator. Our model also predicts that these circuits are highly sensitive to promoter leak, but that promoter leak can be offset with active degradation of dCas. We provide specifications for required fold-repression and dCas degradation rates for several dynamic circuits. Our modeling reveals key engineering requirements and considerations for the construction of dynamic CRISPRi circuits, and provides a roadmap for building those circuits.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/225318DOIDiscussion Paper
ORCID:
AuthorORCID
Clamons, Samuel E.0000-0002-7993-2278
Murray, Richard M.0000-0002-5785-7481
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. bioRxiv preprint first posted online Nov. 27, 2017. This work was supported by the Human Frontiers Science Program, and by National Science Foundation award number 1317694.
Funders:
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
NSFCCF-1317694
Record Number:CaltechAUTHORS:20181031-100007899
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20181031-100007899
Official Citation:Modeling Dynamic Transcriptional Circuits with CRISPRi. Samuel E Clamons, Richard M Murray. bioRxiv 225318; doi: https://doi.org/10.1101/225318
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90539
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Nov 2018 18:16
Last Modified:01 Nov 2018 18:16

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