Modeling Dynamic Transcriptional Circuits with CRISPRi

Title	Modeling Dynamic Transcriptional Circuits with CRISPRi
Authors	Samuel E Clamons and Richard M Murray
Source	2018 Winter q-bio
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.
Type	Conference paper
URL	https://www.biorxiv.org/content/early/2017/11/27/225318
DOI
Tag	cm18-wqbio
ID	2017k
Funding	HFSP TX-TL
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