Evidence map›Paper›PMID 25894090›Full record

ArticleProtein & cell2015

CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes.

Puping Liang, Yanwen Xu, Xiya Zhang, Chenhui Ding, Rui Huang, Zhen Zhang, Jie Lv, Xiaowei Xie, Yuxi Chen, Yujing Li and 6 more

Open access · diamondAbstract read
In one paragraph

Article in Protein & cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 392 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
392citing papers in PubMed, 2 pooled it
83.3field-weighted citation impact, top 1% 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

392 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,104 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
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332 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Puping Liang *Guangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Yanwen Xu *Guangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Xiya Zhang *Guangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Chenhui Ding *Guangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Rui HuangGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Zhen ZhangGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Jie LvGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Xiaowei XieGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Yuxi ChenGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Yujing LiGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Ying SunGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Yaofu BaiGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Zhou SongyangGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Wenbin MaGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Canquan ZhouGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Junjiu HuangGuangdong Province Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, and Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275 China.
Sun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.

Indexed as

BlastocystCRISPR-Cas SystemsZygoteHemoglobins, AbnormalHumansHemoglobins, Abnormal

Identifiers

PMID25894090
PMCPMC4417674
OpenAlexW2141825721

What OpenQuestion holds

Textmetadata
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.