Evidence map›Paper›PMID 19532138›Full record

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

Identification of protein cofactors necessary for sequence-specific plasmid DNA nuclear import.

Aaron M Miller, Felix M Munkonge, Eric W F W Alton, David A Dean

Open access · bronzeAbstract 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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-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

18 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Electroporation-mediated gene delivery.Advances in genetics · 2015
    Article
  11. Article
  12. Proteomic and functional analyses of protein-DNA complexes during gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2013
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. 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

4 authors at 2 institutions in 2 countries.

Aaron M MillerDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Felix M Munkonge
Eric W F W Alton
David A Dean
Imperial College London · GBNorthwestern University · US

Funding

Alveolar Epithelial Cell-Specific Gene Therapy PlasmidsR01HL081148 · NHLBI · UNIVERSITY OF ROCHESTER · PI DEAN, DAVID A · 2006 to 2010
$1.8M
VASCULAR SMOOTH MUSCLE SPECIFIC GENE THERAPY VECTORSR01HL059956 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI DEAN, DAVID A · 1998 to 2007
$1.8M
NHLBI NIH HHS HL59956NHLBI NIH HHS HL81148NHLBI NIH HHS R01 HL059956NHLBI NIH HHS R01 HL081148
6 · The paper itself

Abstract

Although transfections are routinely used in the laboratory, the mechanism(s) by which exogenous DNA is transported into the nucleus is poorly understood. By improving our understanding of how vectors circumvent the numerous cellular barriers to gene transfer, more efficient gene delivery methods can be devised. We have begun to design plasmid constructs that enter the nucleus of specific cell types in the absence of cell division, thereby enhancing levels of expression. We have shown that inclusion of specific DNA sequences in plasmid constructs mediates nuclear import both in vitro and in vivo. Here, we use plasmid affinity chromatography, mass spectrometry (MS), and live-cell pulldowns of transfected plasmid constructs to identify protein cofactors that interact in a sequence-specific manner with these DNA nuclear targeting sequences (DTSs). Importin beta(1), importin 7, and the small guanosine triphosphatase Ran all demonstrate DTS-specific interaction in both MS and pull-down assays, consistent with our model of plasmid nuclear import. In addition, knockdown of importin beta(1) with small interfering RNA (siRNA) abrogates plasmid nuclear import, indicating that it is a necessary cofactor. Our discovery that specific karyopherins mediate plasmid nuclear import can be used to design more effective vectors for gene delivery.

Indexed as

Active Transport, Cell Nucleusbeta KaryopherinsChromatography, AffinityHumansKaryopherinsMass SpectrometryPlasmidsran GTP-Binding ProteinReceptors, Cytoplasmic and NuclearRNA, Small Interferingbeta KaryopherinsIPO7 protein, humanKaryopherinsran GTP-Binding ProteinReceptors, Cytoplasmic and NuclearRNA, Small Interfering

Identifiers

PMID19532138
PMCPMC2835029
OpenAlexW2064927698

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.