Evidence map›Paper›PMID 26755332›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Genome-wide Profiling Reveals Remarkable Parallels Between Insertion Site Selection Properties of the MLV Retrovirus and the piggyBac Transposon in Primary Human CD4(+) T Cells.

Andreas Gogol-Döring, Ismahen Ammar, Saumyashree Gupta, Mario Bunse, Csaba Miskey, Wei Chen, Wolfgang Uckert, Thomas F Schulz, Zsuzsanna Izsvák, Zoltán Ivics

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
–field-weighted citation impact
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

106 citing papers in PubMed.

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  15. ThebioRxiv : the preprint server for biology · 2025
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  20. Generation and GMP scale-up of human CAR-T cells using non-viralMolecular therapy. Methods & clinical development · 2025
    Article

46 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

10 authors.

Andreas Gogol-DöringInstitute of Computer Science, Martin Luther University Halle-Wittenberg, Wittenberg, Germany.
Ismahen AmmarMax Delbrück Center for Molecular Medicine, Berlin, Germany.
Saumyashree GuptaInstitute of Virology, Hannover Medical School, Hannover, Germany.
Mario BunseMax Delbrück Center for Molecular Medicine, Berlin, Germany.
Csaba MiskeyDivision of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.
Wei ChenMax Delbrück Center for Molecular Medicine, Berlin, Germany.
Wolfgang UckertMax Delbrück Center for Molecular Medicine, Berlin, Germany.
Thomas F SchulzInstitute of Virology, Hannover Medical School, Hannover, Germany.
Zsuzsanna IzsvákMax Delbrück Center for Molecular Medicine, Berlin, Germany.
Zoltán IvicsDivision of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The inherent risks associated with vector insertion in gene therapy need to be carefully assessed. We analyzed the genome-wide distributions of Sleeping Beauty (SB) and piggyBac (PB) transposon insertions as well as MLV retrovirus and HIV lentivirus insertions in human CD4(+) T cells with respect to a panel of 40 chromatin states. The distribution of SB transposon insertions displayed the least deviation from random, while the PB transposon and the MLV retrovirus showed unexpected parallels across all chromatin states. Both MLV and PB insertions are enriched at transcriptional start sites (TSSs) and co-localize with BRD4-associated sites. We demonstrate physical interaction between the PB transposase and bromodomain and extraterminal domain proteins (including BRD4), suggesting convergent evolution of a tethering mechanism that directs integrating genetic elements into TSSs. We detect unequal biases across the four systems with respect to targeting genes whose deregulation has been previously linked to serious adverse events in gene therapy clinical trials. The SB transposon has the highest theoretical chance of targeting a safe harbor locus in the human genome. The data underscore the significance of vector choice to reduce the mutagenic load on cells in clinical applications.

Indexed as

DNA Transposable ElementsGenome-Wide Association StudyVirus IntegrationAnimalsBinding SitesCD4-Positive T-LymphocytesChromatinChromosome MappingGene Expression RegulationGenetic VectorsHumansLeukemia Virus, MurineProtein BindingTranscription Initiation SiteTransposasesChromatinDNA Transposable ElementsTransposases

Identifiers

PMID26755332
PMCPMC4786924

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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.