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Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking

Clamons, Samuel and Murray, Richard (2019) Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20190731-095458774

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Abstract

Synthetic transcriptional networks built from CRISPR-based repressors (CRISPRi) rely on shared use of a core dCas9 protein. In E. coli, CRISPRi cannot sup- port more than about a dozen simultaneous gRNAs before the fold repression of any individual gRNA drops below 10x. We show with a simple model based on previous characterization of competition in CRISPRi that activation by CRISPR-based activators (CRISPRa) is much less sensitive to dCas9 bottle- necking than CRISPRi. We predict that E. coli should be able to support dozens to hundreds of CRISPRa gRNAs at > 10-fold activation.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/719278DOIDiscussion Paper
ORCID:
AuthorORCID
Clamons, Samuel0000-0002-7993-2278
Murray, Richard0000-0002-5785-7481
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 4.0 International license. bioRxiv preprint first posted online Jul. 30, 2019.
Record Number:CaltechAUTHORS:20190731-095458774
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190731-095458774
Official Citation:Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking. Samuel Clamons, Richard Murray. bioRxiv 719278; doi: https://doi.org/10.1101/719278
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:97545
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:31 Jul 2019 20:01
Last Modified:21 Dec 2020 21:05

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