Evidence map›Paper›PMID 11406766›Full record

ArticleGene therapy2001

Triggered intracellular activation of disulfide crosslinked polyelectrolyte gene delivery complexes with extended systemic circulation in vivo.

D Oupický, R C Carlisle, L W Seymour

Abstract read
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In one paragraph

Article in Gene therapy, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.9field-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

35 citing papers in PubMed, 152 citations in OpenAlex.

  1. Highly efficient production of HIV-1Journal of virology · 2025
    Article
  2. Photochemical Stabilization of Self-Assembled Spherical Nucleic Acids.Small (Weinheim an der Bergstrasse, Germany) · 2025
    Article
  3. Article
  4. Article
  5. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Decationized polyplexes as stable and safe carrier systems for improved biodistribution in systemic gene therapy.Journal of controlled release : official journal of the Controlled Release Society · 2014
    Article
  14. Article
  15. Review
  16. Article
  17. Well-defined cross-linked antioxidant nanozymes for treatment of ischemic brain injury.Journal of controlled release : official journal of the Controlled Release Society · 2012
    Article
  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 1 institution in 1 country.

D OupickýCRC Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TA, UK.
R C Carlisle
L W Seymour
University of Birmingham · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have developed polyelectrolyte gene delivery vectors that display good extracellular stability and are activated intracellularly to permit transgene expression. The strategy comprises covalent crosslinking of primary amines in poly-L-lysine/DNA complexes with a crosslinking agent that can later be cleaved by reduction. Crosslinked complexes maintained the same size and surface charge but showed increased stability against polyelectrolyte exchange with poly-L-aspartic acid. Surface modification with polyethyleneglycol improved solubility and masked their positive surface charge. Crosslinked complexes showed 10-fold increased plasma circulation following intravenous administration to Balb/c mice. In the absence of chloroquine, the levels of transgene expression in B16F10 murine melanoma cells were similar for crosslinked and non-crosslinked complexes, however, chloroquine selectively potentiated transgene expression by the non-crosslinked complexes. Cellular uptake of the complexes was the same, irrespective of crosslinking. Following microinjection into the cytoplasm of Xenopus oocytes, or the cytoplasm or nucleus of Rat-1 fibroblasts, crosslinked complexes mediated the same transgene expression as non-crosslinked complexes, indicating crosslinked complexes are rapidly reduced and activated intracellularly. We therefore hypothesize that the lower in vitro transfection activity of crosslinked complexes in the presence of chloroquine is due to reduced transfer from endosome to cytoplasm, mainly due to increased stability against destabilization by chloroquine. The extended systemic circulation together with triggered intracellular activation makes these complexes a promising system for targeted gene delivery in vivo.

Indexed as

Gene Transfer TechniquesAnimalsCross-Linking ReagentsDisulfidesDNAElectrolytesFemaleGenetic VectorsLiverMiceMice, Inbred BALB CMicroinjectionsPolyethylene GlycolsPolylysineSodium ChlorideSolubilityCross-Linking ReagentsDisulfidesDNAElectrolytesPolyethylene GlycolsPolylysineSodium Chloride

Identifiers

PMID11406766
OpenAlexW2313680690

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.