Evidence map›Paper›PMID 28666380›Full record

ArticleNucleic acids research2017

Comparative analysis of chimeric ZFP-, TALE- and Cas9-piggyBac transposases for integration into a single locus in human cells.

Wentian Luo, Daniel L Galvan, Lauren E Woodard, Dan Dorset, Shawn Levy, Matthew H Wilson

Open access · goldAbstract readComparative Study
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

28 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
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  7. International journal of molecular sciences · 2023
    Article
  8. Article
  9. Article
  10. Gene editing and its applications in biomedicine.Science China. Life sciences · 2022
    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

6 authors at 3 institutions in 1 country.

Wentian LuoDepartment of Veterans Affairs, Nashville, TN 37212 USA and Department of Medicine, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Daniel L GalvanCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Lauren E WoodardDepartment of Veterans Affairs, Nashville, TN 37212 USA and Department of Medicine, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Dan DorsetHudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
Shawn LevyHudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
Matthew H WilsonDepartment of Veterans Affairs, Nashville, TN 37212 USA and Department of Medicine, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Vanderbilt University Medical Center · USHudsonAlpha Institute for Biotechnology · USBaylor College of Medicine · US

Funding

Novel cell therapy for sustained therapeutic protein delivery in vivoR01DK093660 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, MATTHEW H · 2012 to 2022
$3.4M
Kidney specific site-directed integration for cystinuriaI01BX002190 · VA · VETERANS HEALTH ADMINISTRATION · PI WILSON, MATTHEW H · 2014 to 2017
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In Situ Reprogramming of Induced Nephron Progenitor Cells for Kidney RegenerationIK2BX002797 · VA · VETERANS HEALTH ADMINISTRATION · PI WOODARD, LAUREN ELIZABETH · 2015 to 2020
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BLRD VA I01 BX002190BLRD VA IK2 BX002797NIDDK NIH HHS R01 DK093660
6 · The paper itself

Abstract

Integrating DNA delivery systems hold promise for many applications including treatment of diseases; however, targeted integration is needed for improved safety. The piggyBac (PB) transposon system is a highly active non-viral gene delivery system capable of integrating defined DNA segments into host chromosomes without requiring homologous recombination. We systematically compared four different engineered zinc finger proteins (ZFP), four transcription activator-like effector proteins (TALE), CRISPR associated protein 9 (SpCas9) and the catalytically inactive dSpCas9 protein fused to the amino-terminus of the transposase enzyme designed to target the hypoxanthine phosphoribosyltransferase (HPRT) gene located on human chromosome X. Chimeric transposases were evaluated for expression, transposition activity, chromatin immunoprecipitation at the target loci, and targeted knockout of the HPRT gene in human cells. One ZFP-PB and one TALE-PB chimera demonstrated notable HPRT gene targeting. In contrast, Cas9/dCas9-PB chimeras did not result in gene targeting. Instead, the HPRT locus appeared to be protected from transposon integration. Supplied separately, PB permitted highly efficient isolation of Cas9-mediated knockout of HPRT, with zero transposon integrations in HPRT by deep sequencing. In summary, these tools may allow isolation of 'targeted-only' cells, be utilized to protect a genomic locus from transposon integration, and enrich for Cas9-mutated cells.

Indexed as

Gene Transfer TechniquesBacterial ProteinsCell Line, TumorCRISPR-Associated Protein 9CRISPR-Cas SystemsDNA Transposable ElementsEndonucleasesGene Knockout TechniquesGene TargetingHumansHypoxanthine PhosphoribosyltransferaseMutagenesis, InsertionalRecombinant Fusion ProteinsReproducibility of ResultsTranscription Activator-Like Effector NucleasesTranscription Activator-Like EffectorsBacterial ProteinsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9DNA Transposable ElementsEndonucleasesHypoxanthine PhosphoribosyltransferaseRecombinant Fusion ProteinsTranscription Activator-Like Effector NucleasesTranscription Activator-Like EffectorsTransposases

Identifiers

PMID28666380
PMCPMC5737283
OpenAlexW2731089673

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.