Evidence map›Paper›PMID 25511918›Full record

ArticlePharmaceutical research2015

Dependence of PEI and PAMAM Gene Delivery on Clathrin- and Caveolin-Dependent Trafficking Pathways.

Mark E Hwang, Rahul K Keswani, Daniel W Pack

Abstract read
In one paragraph

Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

22 citing papers in PubMed, 44 citations in OpenAlex.

  1. Penetratin Decoration Increases RNAi Silencing Effects of Polymeric Carriers.Chemistry of materials : a publication of the American Chemical Society · 2026
    Article
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  9. Review
  10. A Polymeric Nanoparticle Formulation for Targeted mRNA Delivery to Fibroblasts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. The Effect of Size and Shape of RNA Nanoparticles on Biodistribution.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  17. Review
  18. Article
  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

3 authors at 2 institutions in 1 country.

Mark E HwangDepartment of Bioengineering, University of Illinois Urbana-Champaign, Urbana, Illinois, 61801, USA.
Rahul K Keswani
Daniel W Pack
University of Illinois Urbana-Champaign · USUniversity of Kentucky · US

Funding

Effects of Uptake Mechanism on Polyplex Design CriteriaR01GM085222 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI PACK, DANIEL W · 2009 to 2012
$1.2M
Targeted Delivery, Trafficking, and Vector Design for Respiratory Gene TransferF30DK083875 · NIDDK · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI HWANG, MARK EUGENE · 2009 to 2014
$274k
NIDDK NIH HHS DK083875NIDDK NIH HHS F30 DK083875NIGMS NIH HHS GM085222NIGMS NIH HHS R01 GM085222
6 · The paper itself

Abstract

purposeNon-viral gene delivery vehicles such as polyethylenimine and polyamidoamine dendrimer effectively condense plasmid DNA, facilitate endocytosis, and deliver nucleic acid cargo to the nucleus in vitro. Better understanding of intracellular trafficking mechanisms involved in polymeric gene delivery is a prerequisite to clinical application. This study investigates the role of clathrin and caveolin endocytic pathways in cellular uptake and subsequent vector processing.

methodsWe formed 25-kD polyethylenimine (PEI) and generation 4 (G4) polyamidoamine (PAMAM) polyplexes at N/P 10 and evaluated internalization pathways and gene delivery in HeLa cells. Clathrin- and caveolin-dependent endocytosis inhibitors were used at varying concentrations to elucidate the roles of these important pathways.

resultsPEI and PAMAM polyplexes were internalized by both pathways. However, the amount of polyplex internalized poorly correlated with transgene expression. While the caveolin-dependent pathway generally led to effective gene delivery with both polymers, complete inhibition of the clathrin-dependent pathway was also deleterious to transfection with PEI polyplexes. Inhibition of one endocytic pathway may lead to an overall increase in uptake via unaffected pathways, suggesting the existence of compensatory endocytic mechanisms.

conclusionsThe well-studied clathrin- and caveolin-dependent endocytosis pathways are not necessarily independent, and perturbing one mechanism of trafficking influences the larger trafficking network.

Indexed as

EndocytosisCaveolinsClathrinDendrimersDose-Response Relationship, DrugGene Expression RegulationGenes, ReporterHeLa CellsHumansLuciferases, FireflyPlasmidsPolyethyleneimineTransfectionCaveolinsClathrinDendrimersLuciferases, FireflyPAMAM StarburstPolyethyleneimine

Identifiers

PMID25511918
PMCPMC4425630
OpenAlexW1982381743

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.