Evidence map›Paper›PMID 30834641›Full record

ArticleAngewandte Chemie (International ed. in English)2019

A Singular System with Precise Dosing and Spatiotemporal Control of CRISPR-Cas9.

Debasish Manna, Basudeb Maji, Soumyashree A Gangopadhyay, Kurt J Cox, Qingxuan Zhou, Benjamin K Law, Ralph Mazitschek, Amit Choudhary

Open access · greenAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. A supramolecular approach towards the photorelease of encapsulated caged acids in water: 7-diethylaminothio-4-coumarinyl molecules as triggers.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2024
    Article
  7. Review
  8. Review
  9. Site-Specific mAngewandte Chemie (International ed. in English) · 2023
    Article
  10. Review
  11. Review
  12. Article
  13. Spatiotemporal control of CRISPR/Cas9 gene editing.Signal transduction and targeted therapy · 2021
    Review
  14. Article
  15. Controlling and enhancing CRISPR systems.Nature chemical biology · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Efficient Genome Editing inMicroorganisms · 2020
    Article
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

8 authors at 1 institution in 1 country.

Debasish MannaChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID 0000-0003-4446-7318
Basudeb MajiChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Soumyashree A GangopadhyayChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Kurt J CoxChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Qingxuan ZhouChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Benjamin K LawChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Ralph MazitschekChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Amit ChoudharyChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID 0000-0002-8437-0150
Broad Institute · US

Funding

Identification of potent small molecule inhibitors of Cas9R21AI126239 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI CHOUDHARY, AMIT · 2016 to 2017
$488k
Army Research Office Award W911NF1610586Defense Advanced Research Projects Agency N66001-17-2-4055NIAID NIH HHS R21 AI126239
6 · The paper itself

Abstract

Several genome engineering applications of CRISPR-Cas9, an RNA-guided DNA endonuclease, require precision control of Cas9 activity over dosage, timing, and targeted site in an organism. While some control of Cas9 activity over dose and time have been achieved using small molecules, and spatial control using light, no singular system with control over all the three attributes exists. Furthermore, the reported small-molecule systems lack wide dynamic range, have background activity in the absence of the small-molecule controller, and are not biologically inert, while the optogenetic systems require prolonged exposure to high-intensity light. We previously reported a small-molecule-controlled Cas9 system with some dosage and temporal control. By photocaging this Cas9 activator to render it biologically inert and photoactivatable, and employing next-generation protein engineering approaches, we have built a system with a wide dynamic range, low background, and fast photoactivation using a low-intensity light while rendering the small-molecule activator biologically inert. We anticipate these precision controls will propel the development of practical applications of Cas9.

Indexed as

Binding SitesCell Line, TumorCRISPR-Cas SystemsCrystallography, X-RayGene EditingHumansProtein EngineeringProtein Structure, TertiaryTetrahydrofolate DehydrogenaseTranscriptional ActivationTrimethoprimUltraviolet RaysTetrahydrofolate DehydrogenaseTrimethoprimCRISPR-Cas9genome editingphotocagingtranscriptiontrimethoprim

Identifiers

PMID30834641
PMCPMC7067309
OpenAlexW2919028532

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.