Evidence map›Paper›PMID 18496575›Full record

ArticleGene therapy2008

Cell-specific nuclear import of plasmid DNA in smooth muscle requires tissue-specific transcription factors and DNA sequences.

A M Miller, D A Dean

Open access · bronzeAbstract read
In one paragraph

Article in Gene therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.7field-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

26 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Lipid-based nucleic acid therapeutics with in vivo efficacy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023
    Review
  5. Review
  6. Review
  7. Leptomycin B alters the subcellular distribution of CRM1 (Exportin 1).Biochemical and biophysical research communications · 2017
    Article
  8. Article
  9. Advanced Design of Dumbbell-shaped Genetic Minimal Vectors Improves Non-coding and Coding RNA Expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Article
  10. Article
  11. Electroporation-mediated gene delivery.Advances in genetics · 2015
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Gene therapy for ALI/ARDS.Critical care clinics · 2011
    Review
  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

2 authors at 1 institution in 1 country.

A M MillerDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
D A Dean
Northwestern University · US

Funding

Role of LUBAC and Na K-ATPase in Acute Lung InjuryP01HL071643 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHANDEL, NAVDEEP S · 2003 to 2019
$30.8M
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 P01 HL071643NHLBI NIH HHS R01 HL059956
6 · The paper itself

Abstract

Two shortcomings of nonviral gene therapy are a lack of tissue-specific targeting of vectors and low levels of gene transfer. Our laboratory has begun to address these limitations by designing plasmids that enter the nucleus of specific cell types in the absence of cell division, thereby enhancing expression in a controlled manner. We have shown that a 176 bp portion of the smooth muscle gamma-actin (SMGA) promoter can mediate plasmid nuclear import specifically in smooth muscle cells (SMCs). Here, we demonstrate that the binding sites for serum response factor (SRF) and NKX3-1/3-2 within this DNA nuclear targeting sequence (DTS) are required for plasmid nuclear import. Knockdown of these factors with siRNA abrogates plasmid nuclear import, indicating that they are necessary cofactors. In addition, coinjection of recombinant SRF and Nkx3.2 with the vector in TC7 epithelial cells rescues import. Finally, we show that the SRF nuclear localization sequence (NLS) is required for vector nuclear import. We propose that SRF and NKX3-1/3-2 bind the SMGA DTS in the cytoplasm, thus coating the plasmid with NLSs that mediate translocation across the nuclear pore complex. This discovery could aid in the development of more efficient nonviral vectors for gene transfer to SMCs.

Indexed as

Active Transport, Cell NucleusPlasmidsTransfectionAnimalsBase SequenceCell LineElectroporationGene ExpressionHomeodomain ProteinsMicroscopy, FluorescenceMolecular Sequence DataMuscle, SmoothNuclear Localization SignalsPromoter Regions, GeneticRNA InterferenceRNA, Small InterferingHomeodomain ProteinsNkx3-2 protein, mouseNuclear Localization SignalsRNA, Small InterferingSerum Response FactorTranscription Factors

Identifiers

PMID18496575
PMCPMC3744158
OpenAlexW2072139568

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.