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Modeling Dynamic Transcriptional Circuits with CRISPRi

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 (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20181031-100007899

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Abstract

Targeted transcriptional repression with catalytically inactive Cas9 (CRISPRi) promises to reproduce the functions of traditional synthetic transcriptional circuits, but with better orthogonality, programmability, and extensibility. However, CRISPRi lacks obvious cooperativity–a feature classically considered critical for several classic gene regulatory circuits. We use a simple dynamical model of CRISPRi to show that it can be used to build repressilators, toggle switches, and incoherent feed-forward loops. We also show that the function some of these circuits are expected to be sensitive to several key parameters, and we provide specifications for those parameters. 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, Samuel0000-0002-7993-2278
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. Version 1 - November 27, 2017; Version 2 - February 11, 2022. This work was supported by the Human Frontiers Science Program, by National Science Foundation award number 1317694, and by the Institute for Collaborative Biotechnologies through contract W911NF-19-D-0001 from the U.S. Army Research Office. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
NSFCCF-1317694
Army Research Office (ARO)W911NF-19-D-0001
DOI:10.1101/225318
Record Number:CaltechAUTHORS:20181031-100007899
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20181031-100007899
Official Citation:Modeling Dynamic Transcriptional Circuits with CRISPRi. Samuel 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:17 Feb 2022 00:08

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