Modeling Dynamic Transcriptional Circuits with CRISPRi
- Creators
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Clamons, Samuel
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Murray, Richard M.
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.
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.Attached Files
Submitted - 225318v2.full.pdf
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Additional details
- Eprint ID
- 90539
- Resolver ID
- CaltechAUTHORS:20181031-100007899
- Human Frontier Science Program
- CCF-1317694
- NSF
- W911NF-19-D-0001
- Army Research Office (ARO)
- Created
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2018-11-01Created from EPrint's datestamp field
- Updated
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2022-02-17Created from EPrint's last_modified field