Evidence map›Paper›PMID 32644042›Full record

ArticleeLife2020

A high-throughput small molecule screen identifies farrerol as a potentiator of CRISPR/Cas9-mediated genome editing.

Weina Zhang, Yu Chen, Jiaqing Yang, Jing Zhang, Jiayu Yu, Mengting Wang, Xiaodong Zhao, Ke Wei, Xiaoping Wan, Xiaojun Xu and 4 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Impaired end joining induces cardiac atrophy in a Hutchinson-Gilford progeria mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  16. Article
  17. Article
  18. Gene Editing in Hematopoietic Stem Cells.Advances in experimental medicine and biology · 2023
    Review
  19. Article
  20. 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

14 authors at 3 institutions in 1 country.

Weina Zhang *Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID 0000-0003-2852-4079
Yu Chen *Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID 0000-0002-9661-3914
Jiaqing YangClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Jing ZhangClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Jiayu YuClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Mengting WangClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Xiaodong ZhaoClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Ke WeiClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Xiaoping WanClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Xiaojun XuState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Ying JiangClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Jiayu ChenClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID 0000-0003-4755-8901
Shaorong GaoClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID 0000-0003-1041-3928
Zhiyong MaoClinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.ORCID 0000-0002-5298-1918
Shanghai First Maternity and Infant Hospital · CNChina Pharmaceutical University · CNTongji University · CN

Funding

Chinese National Program on Key Basic Research Project 2016YFA0100400Chinese National Program on Key Basic Research Project 2017YFA010330Chinese National Program on Key Basic Research Project 2017YFA0103300Chinese National Program on Key Basic Research Project 2018YFC2000100National Science Foundation of China 31721003National Science Foundation of China 31871438National Science Foundation of China 31871446National Science Foundation of China 81972457Program of Shanghai Academic Research Leader 19XD1403000Shanghai Municipal Medical and Health Discipline Construction Projects 2017ZZ02015Shanghai Rising-Star Program 19QA1409600"Shuguang Program" of Shanghai Education Development Foundation and Shanghai Municipal Education Commission 19SG18Shuguang Program" of Shanghai Education Development Foundation and Shanghai Municipal Education Commission" 19SG18the Fundamental Research Funds for the Central Universities, Program of Shanghai Academic Research Leader 19XD1403000the key project of the Science and Technology of Shanghai Municipality 19JC1415300The key project of the Science and Technology of Shanghai Municipality 19JC1415300the National Science Foundation of China 31721003the National Science Foundation of China 31871438the National Science Foundation of China 31871446the National Science Foundation of China 81972457the Shanghai Municipal Medical and Health Discipline Construction Projects 2017ZZ02015the Shanghai Rising-Star Program 19QA1409600the Young Elite Scientist Sponsorship Program by CAST 2018QNRC001The Young Elite Scientist Sponsorship Program by CAST 2018QNRC001
6 · The paper itself

Abstract

Directly modulating the choice between homologous recombination (HR) and non-homologous end joining (NHEJ) - two independent pathways for repairing DNA double-strand breaks (DSBs) - has the potential to improve the efficiency of gene targeting by CRISPR/Cas9. Here, we have developed a rapid and easy-to-score screening approach for identifying small molecules that affect the choice between the two DSB repair pathways. Using this tool, we identified a small molecule, farrerol, that promotes HR but does not affect NHEJ. Further mechanistic studies indicate that farrerol functions through stimulating the recruitment of RAD51 to DSB sites. Importantly, we demonstrated that farrerol effectively promotes precise targeted integration in human cells, mouse cells and mouse embryos at multiple genomic loci. In addition, treating cells with farrerol did not have any obvious negative effect on genomic stability. Moreover, farrerol significantly improved the knock-in efficiency in blastocysts, and the subsequently generated knock-in mice retained the capacity for germline transmission.

Indexed as

CRISPR-Cas SystemsGene EditingHigh-Throughput Screening AssaysAnimalsChromonesHEK293 CellsHumansMiceChromonesfarrerolcell biologyCRISPR/Cas9farrerolgeneticsgenomicshomologous recombination (HR)humanknock-inmousenon-homologous end joining (NHEJ)

Identifiers

PMID32644042
PMCPMC7380943
OpenAlexW3042200620

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.