Evidence map›Paper›PMID 25952271›Full record

ArticleACS nano2015

Quantitative Measurement of Cationic Polymer Vector and Polymer-pDNA Polyplex Intercalation into the Cell Plasma Membrane.

Sriram Vaidyanathan, Kevin B Anderson, Rachel L Merzel, Binyamin Jacobovitz, Milan P Kaushik, Christina N Kelly, Mallory A van Dongen, Casey A Dougherty, Bradford G Orr, Mark M Banaszak Holl

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS nano, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

13 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Engineering poly- and micelleplexes for nucleic acid delivery - A reflection on their endosomal escape.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Review
  6. Article
  7. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. 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

10 authors at 1 institution in 1 country.

Sriram Vaidyanathan†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Kevin B Anderson†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Rachel L Merzel†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Binyamin Jacobovitz†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Milan P Kaushik†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Christina N Kelly†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Mallory A van Dongen†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Casey A Dougherty†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Bradford G Orr†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
Mark M Banaszak Holl†Departments of Biomedical Engineering, ‡Chemistry, and §Physics, and ∥the Programs in Applied Physics and ⊥Biophysics, University of Michigan, Ann Arbor, Michigan 48109, United States.
University of Michigan–Ann Arbor · US

Funding

The Role of Cell Membrane Disruption in Non-Viral Vector Oligonucleotide DeliveryR01EB005028 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BANASZAK HOLL, MARK M · 2006 to 2013
$2.8M
NIBIB NIH HHS EB005028NIBIB NIH HHS R01 EB005028
6 · The paper itself

Abstract

Cationic gene delivery agents (vectors) are important for delivering nucleotides, but are also responsible for cytotoxicity. Cationic polymers (L-PEI, jetPEI, and G5 PAMAM) at 1× to 100× the concentrations required for translational activity (protein expression) induced the same increase in plasma membrane current of HEK 293A cells (30-50 nA) as measured by whole cell patch-clamp. This indicates saturation of the cell membrane by the cationic polymers. The increased currents induced by the polymers are not reversible for over 15 min. Irreversibility on this time scale is consistent with a polymer-supported pore or carpet model and indicates that the cell is unable to clear the polymer from the membrane. For polyplexes, although the charge concentration was the same (at N/P ratio of 10:1), G5 PAMAM and jetPEI polyplexes induced a much larger current increase (40-50 nA) than L-PEI polyplexes (<20 nA). Both free cationic lipid and lipid polyplexes induced a lower increase in current than cationic polymers (<20 nA). To quantify the membrane bound material, partition constants were measured for both free vectors and polyplexes into the HEK 293A cell membrane using a dye influx assay. The partition constants of free vectors increased with charge density of the vectors. Polyplex partition constants did not show such a trend. The long lasting cell plasma permeability induced by exposure to the polymer vectors or the polyplexes provides a plausible mechanism for the toxicity and inflammatory response induced by exposure to these materials.

Indexed as

CationsCell MembraneCell Membrane PermeabilityDNAGenetic VectorsGene Transfer TechniquesHEK293 CellsHumansIntercalating AgentsParticle SizePolymersPorositySurface PropertiesCationsDNAIntercalating AgentsPolymersgene deliverygene therapypolymer−cell membrane interactionspolymer-membrane partitionpolyplex−membrane partitionstable pore modelwhole cell patch clamp

Identifiers

PMID25952271
PMCPMC4771022
OpenAlexW2471890311

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.