Evidence map›Paper›PMID 28809467›Full record

ArticleACS chemical biology2018

Multidimensional Control of Cas9 by Evolved RNA Polymerase-Based Biosensors.

Jinyue Pu, Kaitlin Kentala, Bryan C Dickinson

Abstract read
In one paragraph

Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 35 citations in OpenAlex.

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  14. Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Jinyue PuDepartment of Chemistry, The University of Chicago , Chicago, Illinois 60637, United States.
Kaitlin KentalaDepartment of Chemistry, The University of Chicago , Chicago, Illinois 60637, United States.
Bryan C DickinsonDepartment of Chemistry, The University of Chicago , Chicago, Illinois 60637, United States.ORCID 0000-0002-9616-1911
University of Chicago · US

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI CHIEN-MIN KAO · 1985 to 2026
$122.1M
Rapid selection approaches to understand and reprogram proteins and peptidesR35GM119840 · NIGMS · UNIVERSITY OF CHICAGO · PI Bryan Dickinson · 2016 to 2026
$4.8M
Predoctoral Training Program in Chemistry & BiologyT32GM008720 · NIGMS · UNIVERSITY OF CHICAGO · PI PICCIRILLI, JOSEPH ANTHONY · 1999 to 2020
$4.7M
NCI NIH HHS P30 CA014599NIGMS NIH HHS R35 GM119840NIGMS NIH HHS T32 GM008720
6 · The paper itself

Abstract

Systems to control Cas9 with spatial and temporal precision offer opportunities to decrease side effects, protect sensitive tissues, and create gene therapies that are only activated at defined times and places. Here, we present the design of new Cas9 controllers based on RNA polymerase (RNAP)-based biosensors that produce gRNAs, thereby regulating target knockout. After development and validation of a new abscisic acid-inducible biosensor to control Cas9, we lowered the background of the system using continuous evolution. To showcase the versatility of the approach, we designed biosensors that measure medically relevant protein-protein interactions to drive knockout. Finally, to test whether orthogonal RNAP biosensors could integrate multiple input signals to drive multiple gRNA-based outputs with a single Cas9 protein, we designed an "on-switch/off switch" controller. The addition of one input activates the "on switch" and induces knockout, while the addition of a second input activates the "off switch" and produces a gRNA that directs the Cas9 protein to degrade the "on switch" gRNA vector, thereby deactivating it. This combined activation and deactivation system displayed very low background and inducible target knockout using different combinations of small-molecule treatment. Our results establish engineered RNAP biosensors as deployable Cas9 control elements and open up new opportunities for driving genetic editing technologies by diverse input signals.

Indexed as

Abscisic AcidBacterial ProteinsBH3 Interacting Domain Death Agonist ProteinBiosensing TechniquesComputers, MolecularCRISPR-Associated ProteinsCRISPR-Cas SystemsDNA-Directed RNA PolymerasesEndonucleasesGene Knockout TechniquesHEK293 CellsHumansLogicProtein EngineeringProto-Oncogene Proteins c-bcl-2RNA, Guide, CRISPR-Cas SystemsAbscisic AcidBacterial ProteinsBH3 Interacting Domain Death Agonist ProteinCRISPR-Associated ProteinsDNA-Directed RNA PolymerasesEndonucleasesProto-Oncogene Proteins c-bcl-2RNA, Guide, CRISPR-Cas Systems

Identifiers

PMID28809467
PMCPMC5828011
OpenAlexW2747242121

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.