Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking
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| Title | Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking |
|---|---|
| Authors | Samuel Clamons and Richard Murray |
| Source | bioRxiv preprint |
| Abstract | Synthetic transcriptional networks built from CRISPR-based repressors (CRISPRi) rely on shared use of a core dCas9 protein. In E. coli, CRISPRi cannot support 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. |
| Type | Preprint |
| URL | https://www.biorxiv.org/content/10.1101/719278v2 |
| DOI | |
| Tag | CM19-biorxiv |
| ID | 2019g |
| Funding | ICB Network19 |
| Flags | Biocircuits |
