Evidence map›Paper›PMID 18985029›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009

Shielding of sleeping beauty DNA transposon-delivered transgene cassettes by heterologous insulators in early embryonal cells.

Trine Dalsgaard, Brian Moldt, Nynne Sharma, Gernot Wolf, Alexander Schmitz, Finn S Pedersen, Jacob G Mikkelsen

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

21 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Gene therapy for hemoglobinopathies: progress and challenges.Translational research : the journal of laboratory and clinical medicine · 2013
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Hybrid lentiviral vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2010
    Review
  16. Helper-independent piggyBac plasmids for gene delivery approaches: strategies for avoiding potential genotoxic effects.Proceedings of the National Academy of Sciences of the United States of America · 2010
    Article
  17. Article
  18. PiggyBac transposon-based inducible gene expression in vivo after somatic cell gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2009
    Article
  19. Genome-wide mapping of PiggyBac transposon integrations in primary human T cells.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2009
    Article
  20. Beyond the rat models of human neurodegenerative disorders.Cellular and molecular neurobiology · 2009
    Review
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

7 authors at 1 institution in 1 country.

Trine DalsgaardDepartment of Human Genetics, University of Aarhus, Aarhus, Denmark.
Brian Moldt
Nynne Sharma
Gernot Wolf
Alexander Schmitz
Finn S Pedersen
Jacob G Mikkelsen
Aarhus University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Sleeping Beauty (SB) transposon system represents an important alternative to viral integrating vector systems but may, as its viral counterparts, be subject to transcriptional silencing. To investigate shielding of SB-delivered transgene cassettes against transcriptional repression, we establish silencing assays in which SB vector-containing F9 murine teratocarcinoma cell clones are identified by strategies that include or exclude selection for transgene expression. Among clones carrying one or more SB transposon vectors, more than one-third are immediately silenced, and most of the remaining clones move toward silencing during prolonged passage. In line with the lack of an intrinsic ability of SB to resist silencing, we show that the stable transfection rate of SB vectors in F9 cells is significantly improved by flanking the transgene with heterologous 5'-HS4 chicken beta-globin (cHS4) insulators. In approaches based on drug selection and subsequent flow-cytometric detection of transgene expression, clones containing cHS4-insulated vectors are to a much higher degree protected against transcriptional silencing, resulting in long-term expression of the fluorescent marker. Our findings demonstrate that SB vectors, prone for transcriptional silencing by positional effects in F9 cells, are protected by insulators. We believe that insulated SB-derived vectors will become useful tools in transposon-based transgenesis and therapeutic gene transfer.

Indexed as

Cell Line, TumorDNA Transposable ElementsGenetic VectorsHumansTeratocarcinomaTranscription, GeneticTransposasesDNA Transposable Elementssleeping beauty transposase, humanTransposases

Identifiers

PMID18985029
PMCPMC2834987
OpenAlexW2074957003

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.