Evidence map›Paper›PMID 32042045›Full record

ArticleScientific reports2020

Specificity profiling of CRISPR system reveals greatly enhanced off-target gene editing.

Yao Wang, Mingrui Wang, Ting Zheng, Yingzi Hou, Pingjing Zhang, Tao Tang, Jing Wei, Quan Du

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. 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
1.9field-weighted citation impact, top 14% 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, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Emerging Gene Therapeutics for Epidermolysis Bullosa under Development.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Review
  8. Genome Editing and Fatty Liver.Advances in experimental medicine and biology · 2023
    Review
  9. Review
  10. Review
  11. Article
  12. Controlling CRISPR with small molecule regulation for somatic cell genome editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  13. Review
  14. Characterization of in vitro models of SLC30A10 deficiency.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021
    Article
  15. How Zebrafish Can Drive the Future of Genetic-based Hearing and Balance Research.Journal of the Association for Research in Otolaryngology : JARO · 2021
    Review
  16. Article
  17. Single-Base Resolution: Increasing the Specificity of the CRISPR-Cas System in Gene Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  18. Article
  19. Review
  20. Review
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 3 institutions in 1 country.

Yao WangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Mingrui WangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Ting ZhengState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Yingzi HouState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Pingjing ZhangBiomics Biotechnologies co. Ltd, Nantong, 226016, Jiangsu Province, China.
Tao TangDepartment of Obstetrics & Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Jing WeiThe Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
Quan DuState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. quan.du@pku.edu.cn.
Peking University · CNChinese University of Hong Kong · CNNantong Tumor Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To explore the editing specificity of CRISPR/Cpf1 system, effects of target mutation were systematically examined using a reporter activation assay, with a set of single-nucleotide mutated target site. Consistent with our previous study performed with CRISPR/Cas9, a "core" sequence region that is highly sensitive to target mutation was characterized. The region is of 4-nucleotide long, located from +4 to +7 position of the target site, and positioned within a positively charged central channel when assembled into Cpf1 endonuclease. Single-nucleotide mutation at the core sequence could abolish gene editing mediated by a however active sgRNA. With a great majority of the target sites, a kind of 'super' off-target gene editing was observed with both CRISPR/Cpf1 and CRISPR/Cas9. For a given target site, mutation at certain positions led to greatly enhanced off-target gene editing efficacy, even up to 10-fold of that of the fully-matched target. Study further found that these effects were determined by the identity of target nucleotide, rather than the nucleotide of crRNA. This likely suggests that the interactions between target nucleotide and the endonuclease are involved in this process.

Indexed as

Bacterial ProteinsCRISPR-Associated Protein 9CRISPR-Associated ProteinsCRISPR-Cas SystemsEndodeoxyribonucleasesGene EditingHEK293 CellsHumansMutationNucleotidesRNA, Guide, CRISPR-Cas SystemsBacterial ProteinsCas12a proteinCRISPR-Associated Protein 9CRISPR-Associated ProteinsEndodeoxyribonucleasesNucleotidesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID32042045
PMCPMC7010781
OpenAlexW3004567324

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.