Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking: Difference between revisions
From Murray Wiki
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
{{Paper | {{Paper | ||
|Title=Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking | |Title=Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking | ||
|Authors=Samuel Clamons, Richard Murray | |Authors=Samuel Clamons, Richard M. Murray | ||
|Source=bioRxiv preprint | |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. | |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. | ||
Latest revision as of 18:16, 9 October 2022
| 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 M. 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 | |
| Flags | Biocircuits |
