Evidence map›Paper›PMID 28155910›Full record

ArticleScientific reports2017

Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos.

Zhuchi Tu, Weili Yang, Sen Yan, An Yin, Jinquan Gao, Xudong Liu, Yinghui Zheng, Jiezhao Zheng, Zhujun Li, Su Yang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

81 citing papers in PubMed, 133 citations in OpenAlex.

  1. Article
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  5. Review
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  8. AeLife · 2024
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  12. 3 Biotech · 2024
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  13. Article
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  15. Article
  16. Review
  17. Efficient Genome Editing of Mice by CRISPR Electroporation of Zygotes.Journal of visualized experiments : JoVE · 2022
    Article
  18. Review
  19. Review
  20. Article

21 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 2 countries.

Zhuchi TuState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101 China.
Weili YangState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101 China.
Sen YanGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, 510632, China.
An YinState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101 China.
Jinquan GaoState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101 China.
Xudong LiuState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101 China.
Yinghui ZhengState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101 China.
Jiezhao ZhengYuanxi Biotech Inc., Guangzhou, 510663 China.
Zhujun LiYuanxi Biotech Inc., Guangzhou, 510663 China.
Su YangDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Shihua LiDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Xiangyu GuoGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, 510632, China.
Xiao-Jiang LiState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101 China.
Jinan University · CNChinese Academy of Sciences · CNEmory University · USInstitute of Genetics and Developmental Biology · CN

Funding

Neuronal function of huntingtin-associated proteinR01NS036232 · NINDS · EMORY UNIVERSITY · PI ESCAYG, ANDREW P · 1998 to 2021
$6.7M
Nuclear Toxicity of Huntington Disease ProteinR01NS041669 · NINDS · EMORY UNIVERSITY · PI LI, XIAO-JIANG · 2001 to 2015
$4.6M
N-terminal huntingtin and Huntington disease neuropathologyR01NS101701 · NINDS · EMORY UNIVERSITY · PI ESCAYG, ANDREW P · 2017 to 2021
$2.2M
Glial huntingtin and neurodegenerationR01NS095181 · NINDS · EMORY UNIVERSITY · PI WEINSHENKER, DAVID · 2015 to 2019
$1.7M
Polyglutamine Expansion Length Dependent PathologyR01NS095279 · NINDS · EMORY UNIVERSITY · PI WARREN, STEPHEN T. · 2015 to 2019
$1.7M
NINDS NIH HHS R01 NS036232NINDS NIH HHS R01 NS041669NINDS NIH HHS R01 NS095181NINDS NIH HHS R01 NS095279NINDS NIH HHS R01 NS101701
6 · The paper itself

Abstract

CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing.

Indexed as

MosaicismMutationAnimalsBacterial ProteinsCRISPR-Associated Protein 9EndonucleasesGene EditingGene Expression RegulationMolecular BiologyPrimatesProteolysisRecombinant Fusion ProteinsUbiquitinBacterial ProteinsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9EndonucleasesRecombinant Fusion ProteinsUbiquitin

Identifiers

PMID28155910
PMCPMC5290468
OpenAlexW2585802341

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.