Evidence map›Paper›PMID 31685959›Full record

ArticleNature biotechnology2019

A highly soluble Sleeping Beauty transposase improves control of gene insertion.

Irma Querques, Andreas Mades, Cecilia Zuliani, Csaba Miskey, Miriam Alb, Esther Grueso, Markus Machwirth, Tobias Rausch, Hermann Einsele, Zoltán Ivics and 2 more

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

60 citing papers in PubMed, 93 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024
    Review
  13. A novel hyperactive variant of theMolecular therapy. Nucleic acids · 2024
    Article
  14. Review
  15. Article
  16. Engineering of potent CAR NK cells using non-viral Sleeping Beauty transposition from minimalistic DNA vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. Article
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

12 authors at 5 institutions in 1 country.

Irma Querques *Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-1113-2773
Andreas Mades *Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Cecilia Zuliani *Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-6026-7207
Csaba MiskeyDivision of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.ORCID http://orcid.org/0000-0002-7566-9556
Miriam AlbMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0001-6454-9906
Esther GruesoDivision of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.
Markus MachwirthMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Tobias RauschGenomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5773-5620
Hermann EinseleMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Zoltán IvicsDivision of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.ORCID http://orcid.org/0000-0002-7803-6658
Michael HudecekMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany. hudecek_m@ukw.de.ORCID http://orcid.org/0000-0002-2280-2202
Orsolya BarabasStructural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. barabas@embl.de.ORCID http://orcid.org/0000-0002-2873-5872
Universitätsklinikum Würzburg · DEPaul Ehrlich Institut · DEEuropean Molecular Biology Laboratory · DEEuropean Molecular Biology Laboratory · DEUniversitäts-Kinderklinik Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Sleeping Beauty (SB) transposon system is an efficient non-viral gene transfer tool in mammalian cells, but its broad use has been hampered by uncontrolled transposase gene activity from DNA vectors, posing a risk of genome instability, and by the inability to use the transposase protein directly. In this study, we used rational protein design based on the crystal structure of the hyperactive SB100X variant to create an SB transposase (high-solubility SB, hsSB) with enhanced solubility and stability. We demonstrate that hsSB can be delivered with transposon DNA to genetically modify cell lines and embryonic, hematopoietic and induced pluripotent stem cells (iPSCs), overcoming uncontrolled transposase activity. We used hsSB to generate chimeric antigen receptor (CAR) T cells, which exhibit potent antitumor activity in vitro and in xenograft mice. We found that hsSB spontaneously penetrates cells, enabling modification of iPSCs and generation of CAR T cells without the use of transfection reagents. Titration of hsSB to modulate genomic integration frequency achieved as few as two integrations per genome.

Indexed as

Cell EngineeringCell LineCells, CulturedGenetic EngineeringHeLa CellsHumansMutagenesis, InsertionalRecombinant Fusion ProteinsStem CellsTransposasesRecombinant Fusion Proteinssleeping beauty transposase, humanTransposases

Identifiers

PMID31685959
PMCPMC6894935
OpenAlexW2983301825

What OpenQuestion holds

Textmetadata
LicenceTDM
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.