A Model for Resource Competition in CRISPR-Mediated Gene Repression
Name
266015v1.full.pdf
Description
Submitted version
Size
1.46 MB
Format
Adobe PDF
Checksum (MD5)
66f7a56faf65e4539a51ecc090d53b1d
Author(s)
Chen, Pin-Yi
Qian, Yili
Del Vecchio, Domitilla
Date Issued
December 2018
Journal
Proceedings of the IEEE Conference on Decision and Control
Publisher
IEEE
Citation
Chen, Pin-Yi, Qian, Yili and Del Vecchio, Domitilla. 2018. "A Model for Resource Competition in CRISPR-Mediated Gene Repression." Proceedings of the IEEE Conference on Decision and Control, 2018-December.
Version
Original manuscript
Abstract
© 2018 IEEE. CRISPR-mediated gene regulation is known for its ability to control multiple targets simultaneously due to its modular nature: the same dCas9 effector can target different genes simply by changing the associated gRNA. However, multiplexing requires the sharing of limited amounts of dCas9 protein among multiple gRNAs, leading to resource competition. In turn, competition between gRNAs for the same resource may hamper network function. In this work, we develop a general model that takes into account the sharing of limited amounts of dCas9 protein for arbitrary CRISPR-mediated gene repression networks. We demonstrate that, as a result of resource competition, hidden interactions appear, which modifies the intended network regulations. As a case study, we analyze the effects of these hidden interactions on repression cascades. In particular, we illustrate that perfect adaptation to resource fluctuations can be achieved in cascades with an even number of repressors. In contrast, cascades with an odd number of repressors are substantially impacted by resource competition.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1109/cdc.2018.8619016
