Evidence map›Paper›PMID 21716302›Full record

ArticleGene therapy2012

Transcription factor plasmid binding modulates microtubule interactions and intracellular trafficking during gene transfer.

M A Badding, E E Vaughan, D A Dean

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.1field-weighted citation impact, top 25% 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, 50 citations in OpenAlex.

  1. Review
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  18. Non-viral therapeutic approaches to ocular diseases: An overview and future directions.Journal of controlled release : official journal of the Controlled Release Society · 2015
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

M A BaddingDivision of Neonatology, Department of Pediatrics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
E E Vaughan
D A Dean
Northwestern University · US

Funding

VISUAL INDICES OF NEUROTOXICITYP30ES001247 · NIEHS · UNIVERSITY OF ROCHESTER · PI Martha Susiarjo · 1985 to 2026
$42.8M
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
Training in Environment ToxicologyT32ES007026 · NIEHS · UNIVERSITY OF ROCHESTER · PI Alison Elder, Marissa Sobolewski Terry · 1985 to 2026
$20.2M
Cytoplasmic trafficking of non-viral gene therapy vectorsR01EB009903 · NIBIB · UNIVERSITY OF ROCHESTER · PI DEAN, DAVID A · 2009 to 2017
$2.7M
BCL-2, ROS, AND CELL DEATH IN DEVELOPMENTAL TOXICITYR01ES007026 · NIEHS · UNIVERSITY OF WASHINGTON · PI MIRKES, PHILIP E · 1996 to 2002
$1.2M
NHLBI NIH HHS HL71643NHLBI NIH HHS P01 HL071643NIBIB NIH HHS EB9903NIBIB NIH HHS R01 EB009903NIEHS NIH HHS ES01247NIEHS NIH HHS ES07026NIEHS NIH HHS P30 ES001247NIEHS NIH HHS R01 ES007026NIEHS NIH HHS T32 ES007026
6 · The paper itself

Abstract

For non-viral gene delivery to be successful, plasmids must move through the cytoplasm to the nucleus in order to be transcribed. While the cytoskeletal meshwork acts as a barrier to plasmid DNA movement in the cytoplasm, the microtubule network is required for directed plasmid trafficking to the nucleus. We have shown previously that plasmid-microtubule interactions require cytoplasmic adapter proteins such as molecular motors, transcription factors (TFs) and importins. However, not all plasmid sequences support these interactions to allow movement to the nucleus. We now demonstrate that microtubule-DNA interactions can show sequence specificity with promoters containing binding sites for cyclic AMP response-element binding protein (CREB), including the cytomegalovirus immediate early promoter (CMV(iep)). Plasmids containing CREB-binding sites showed stringent interactions in an in vitro microtubule-binding assay. Using microinjection and real-time particle tracking, we show that the inclusion of TF binding sites within plasmids permits cytoplasmic trafficking of plasmids during gene transfer. We found that CREB-binding sites are bound by CREB in the cytoplasm during transfection, and allow for enhanced rates of movement and subsequent nuclear accumulation. Moreover, small interfering RNA knockdown of CREB prevented this enhanced trafficking. Therefore, TF binding sites within plasmids are necessary for interactions with microtubules and enhance movement to the nucleus.

Indexed as

Gene Transfer TechniquesBinding SitesBiological TransportCell LineCell NucleusCyclic AMP Response Element-Binding ProteinCytoplasmEnhancer Elements, GeneticGenetic VectorsHumansMicrotubulesModels, BiologicalPlasmidsPromoter Regions, GeneticProtein BindingTranscription FactorsCyclic AMP Response Element-Binding ProteinTranscription Factors

Identifiers

PMID21716302
PMCPMC4150871
OpenAlexW2009241639

What OpenQuestion holds

Textmetadata
LicenceTDM
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.