Evidence map›Paper›PMID 14724672›Full record

ArticleGene therapy2004

Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation.

Z Wang, P J Troilo, X Wang, T G Griffiths, S J Pacchione, A B Barnum, L B Harper, C J Pauley, Z Niu, L Denisova and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

139 citing papers in PubMed, 318 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. DNA-based delivery of G-CSF as a durable and efficacious approach to treat severe chronic neutropenia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  6. Article
  7. Article
  8. Advances in nucleic acid-based cancer vaccines.Journal of biomedical science · 2025
    Review
  9. Review
  10. Orthogonal transcriptional modulation and gene editing using multiple CRISPR-Cas systems.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  11. Review
  12. Vaccine approaches to treat urothelial cancer.Human vaccines & immunotherapeutics · 2024
    Review
  13. Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024
    Review
  14. Article
  15. Review
  16. Review
  17. Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024
    Review
  18. Review
  19. Review
  20. Review

79 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

17 authors at 3 institutions in 2 countries.

Z WangDepartment of Biologics Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA.
P J Troilo
X Wang
T G Griffiths
S J Pacchione
A B Barnum
L B Harper
C J Pauley
Z Niu
L Denisova
T T Follmer
G Rizzuto
G Ciliberto
E Fattori
N L Monica
S Manam
B J Ledwith
United States Military Academy · USInstitute of Molecular Biology and Pathology · ITMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Plasmid vectors have been widely used for DNA vaccines and gene therapy. Following intramuscular injection, the plasmid that persists is extrachromosomal and integration into host DNA, if it occurs at all, is negligible. However, new technologies for improving DNA delivery could increase the frequency of integration. In the present study, we tested the effect of electroporation on plasmid uptake and potential integration following intramuscular injection in mice, using a plasmid containing the mouse erythropoietin gene. Electroporation increased plasmid tissue levels by approximately six- to 34-fold. Using a quantitative gel-purification assay for integration, electroporation was found to markedly increase the level of plasmid associated with high-molecular-weight genomic DNA. To confirm integration and identify the insertion sites, we developed a new assay - referred to as repeat-anchored integration capture (RAIC) PCR - that is capable of detecting rare integration events in a complex mixture in vivo. Using this assay, we identified four independent integration events. Sequencing of the insertion sites suggested a random integration process, but with short segments of homology between the vector breakpoint and the insertion site in three of the four cases. This is the first definitive demonstration of integration of plasmid DNA into genomic DNA following injection in vivo.

Indexed as

GenomeAnimalsDNAElectroporationErythropoietinGenetic TherapyInjections, IntramuscularMiceMice, Inbred BALB CPolymerase Chain ReactionTransfectionDNAErythropoietin

Identifiers

PMID14724672
OpenAlexW2016110802

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.