Evidence map›Paper›PMID 30646876›Full record

ArticleBMC biotechnology2019

Homologous recombination-mediated targeted integration in monkey embryos using TALE nucleases.

Chu Chu, Zhaohui Yang, Jiayin Yang, Li Yan, Chenyang Si, Yu Kang, Zhenzhen Chen, Yongchang Chen, Weizhi Ji, Yuyu Niu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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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

10 authors at 3 institutions in 2 countries.

Chu ChuYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Zhaohui YangYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Jiayin YangThe Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, SAR, China.
Li YanYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Chenyang SiYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Yu KangYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Zhenzhen ChenYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Yongchang ChenYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Weizhi JiYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.
Yuyu NiuYunnan Key Laboratory of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. niuyy@lpbr.cn.
Kunming University of Science and Technology · CNYunnan Yingmao Biotechnology (China) · CNChinese University of Hong Kong · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNon-human primate (NHP) models can closely mimic human physiological functions and are therefore highly valuable in biomedical research. Genome editing is now developing rapidly due to the precision and efficiency offered by engineered site-specific endonuclease-based systems, such as transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) system. It has been demonstrated that these programmable nucleases can introduce genetic changes in embryos from many species including NHPs. In 2014, we reported the first genetic editing of macaques using TALENs and CRISPR/Cas9. Subsequently, we characterized the phenotype of a methyl CpG binding protein 2 (MECP2)-mutant cynomolgus monkey model of Rett syndrome generated using the TALEN approach. These efforts not only accelerated the advance of modeling genetic diseases in NHPs, but also encouraged us to develop specific gene knock-in monkeys. In this study, we assess the possibility of homologous recombination (HR)-mediated gene replacement using TALENs in monkeys, and generate preimplantation embryos carrying an EmGFP fluorescent reporter constructed in the OCT4 gene.

resultWe assembled a pair of TALENs specific to the first exon of the OCT4 gene and constructed a donor vector consisting of the homology arms cloned from the monkey genome DNA, flanking an EmGFP cassette. Next, we co-injected the TALENs-coding plasmid and donor plasmid into the cytoplasm of 122 zygotes 6-8 h after fertilization. Sequencing and immunofluorescence revealed that the OCT4-EmGFP knock-in allele had been successfully generated by TALENs-mediated HR at an efficiency of 11.3% (7 out of 62) or 11.1% (1 out of 9), respectively, in monkey embryos.

conclusionWe have successfully, for the first time, obtained OCT4-EmGFP knock-in monkey embryos via HR mediated by TALENs. Our results suggest that gene targeting through TALEN-assisted HR is a useful approach to introduce precise genetic modification in NHPs.

Indexed as

Homologous RecombinationAnimalsAnimals, Genetically ModifiedFemaleGene EditingGene Knock-In TechniquesGenotypeGreen Fluorescent ProteinsMacaca fascicularisOctamer Transcription Factor-3Transcription Activator-Like Effector NucleasesGreen Fluorescent ProteinsOctamer Transcription Factor-3Transcription Activator-Like Effector NucleasesGene editingHomologous recombinationNon-human primateTALENs

Identifiers

PMID30646876
PMCPMC6334428
OpenAlexW2917784891

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.