Evidence map›Paper›PMID 14671083›Full record

ArticleJournal of virology2004

Long-term transgene expression in proliferating cells mediated by episomally maintained high-capacity adenovirus vectors.

Florian Kreppel, Stefan Kochanek

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

31 citing papers in PubMed, 75 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Long-term correction of hemophilia B using adenoviral delivery of CRISPR/Cas9.Journal of controlled release : official journal of the Controlled Release Society · 2019
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Innate immunity to adenovirus.Human gene therapy · 2014
    Review
  10. Nanomedicine for gene therapy.Drug delivery and translational research · 2013
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Cocaine hydrolase gene therapy for cocaine abuse.Future medicinal chemistry · 2012
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Development of a hybrid baculoviral vector for sustained transgene expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2009
    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

2 authors at 1 institution in 1 country.

Florian KreppelCenter for Molecular Medicine Cologne, University of Cologne, D-50931 Cologne, Germany.
Stefan Kochanek
University of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High-capacity "gutless" adenovirus vectors (HC-AdV) mediate long-term transgene expression in resting cells in vitro and in vivo because of low toxicity and immunogenicity. However, in proliferating cells, expression is transient since HC-AdV genomes do not possess elements that allow for replication and segregation of the replicated genomes to daughter cells. We developed a binary HC-AdV system that, under certain conditions, allows for significantly prolonged episomal maintenance of HC-AdV genomes in proliferating tissue culture cells, resulting in sustained transgene expression. After transduction of target cells the linear HC-AdV genomes were circularized by the DNA recombinase FLPe, which was expressed from the second HC-AdV. The oriP/EBNA-1 replication system derived from Epstein-Barr virus, as well as the human replication origin from the lamin B2 locus, were used as cis elements to test for replication of the 28-kb circular vector genomes with or without selective pressure. Depending on the system, up to 98% of the circularized genomes were replicated and segregated to daughter cells, as demonstrated by Southern assays and as confirmed by monitoring EGFP transgene expression. Surprisingly, in the absence of FLPe recombinase, a small but significant number of HC-AdV genomes spontaneously circularized after transduction of target cells. These circles, found to contain end-to-end joined adenovirus termini, replicated with increased efficiency compared to vectors circularized by FLPe. After further improvements, this HC-AdV system might be suitable for gene therapy applications requiring long-term transgene expression.

Indexed as

Gene Expression Regulation, ViralGenetic VectorsAdenoviruses, HumanCell DivisionCell Line, TumorEpstein-Barr Virus Nuclear AntigensHeLa CellsHumansLaminsPlasmidsReplication OriginTransduction, GeneticTransgenesVirus ReplicationEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensLamins

Identifiers

PMID14671083
PMCPMC303378
OpenAlexW2115295878

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.