Evidence map›Paper›PMID 20438780›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2010

Reducible DNA nanoparticles enhance in vitro gene transfer via an extracellular mechanism.

Wenchao Sun, Pamela B Davis

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

15 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. A review of the tortuous path of nonviral gene delivery and recent progress.International journal of biological macromolecules · 2021
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Reducible HPMA-co-oligolysine copolymers for nucleic acid delivery.International journal of pharmaceutics · 2012
    Article
  14. Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release.Journal of controlled release : official journal of the Controlled Release Society · 2012
    Article
  15. 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.

Wenchao SunDepartment of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Pamela B Davis
University School · US

Funding

Translational Research in Cystic FibrosisP30DK027651 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI DRUMM, MITCHELL L · 1986 to 2014
$15.6M
GENE THERAPY FOR CYSTIC FIBROSIS VIA THE SEC RECEPTORR01DK058318 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2000 to 2008
$2.8M
Nucleolin-mediated cell entry of DNA nanoparticlesR21DK084371 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2009 to 2010
$432k
NIDDK NIH HHS P30 DK027651NIDDK NIH HHS P30DK27651NIDDK NIH HHS R01 DK058318NIDDK NIH HHS R01DK058318NIDDK NIH HHS R21 DK084371
6 · The paper itself

Abstract

We developed polylysine based DNA nanoparticles (DNA NPs) that contain disulfide linkage in the carrier and demonstrated that this reducible DNA NP enhances in vitro gene transfer via an extracellular mechanism. Polylysine was conjugated through an N-terminal cysteine to a polyethylene glycol chain (PEG) by either a disulfide bond (SS) or a thioether bond (CS), and the resulting PEG-peptide conjugates were used to compact plasmid DNA into reducible SS-DNA NPs or non-reducible CS-DNA NPs with identical physical properties. SS-DNA NPs mediated more than 10-fold higher in vitro gene transfer. Others have suggested that disulfide bonds in synthetic gene carriers undergo cleavage in the reducing environment inside the cell, allowing increased intracellular DNA release. In this study, however, both higher cellular uptake of SS-DNA NPs and inhibition of SS-DNA NP mediated in vitro gene transfer by blocking extracellular free thiols suggested an extracellular mechanism. DePEGylation of SS-DNA NPs by extracellular thiols caused aggregation which might lead to higher cellular uptake and higher transgene expression. A series of SS-DNA NPs prepared with stabilized disulfide bonds survived the extracellular environment without aggregation but lost the superior gene transfer ability, indicating that, in our system, intracellular mechanisms are not involved. These results provided further insight into the mechanisms of in vitro gene transfer enhancement by introducing reducible linkages, contributing to the rational design of more efficient non-viral gene delivery systems.

Indexed as

Gene Transfer TechniquesCell Culture TechniquesCell MembraneCell SurvivalCysteineDNADrug CarriersElectrophoresis, Polyacrylamide GelExtracellular SpaceFlow CytometryHeLa CellsHumansMicroscopy, Electron, TransmissionNanoparticlesPlasmidsPolyethyleneCysteineDNADrug CarriersPolyethylenePolylysineSulfhydryl Compounds

Identifiers

PMID20438780
PMCPMC3031909
OpenAlexW2060088722

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.