Evidence map›Paper›PMID 25253445›Full record

ArticleGene therapy2014

The uptake mechanism of PEGylated DNA polyplexes by the liver influences gene expression.

S Khargharia, N J Baumhover, S T Crowley, J Duskey, K G Rice

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. The reduced-charge melittin analogue MelP5 improves the transfection of non-viral DNA nanoparticles.Journal of peptide science : an official publication of the European Peptide Society · 2022
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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

5 authors at 1 institution in 1 country.

S KharghariaDivision of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
N J BaumhoverDivision of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
S T CrowleyDivision of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
J DuskeyDivision of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
K G RiceDivision of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
University of Iowa · US

Funding

PREDOCTORAL TRAINING PROGRAM IN BIOTECHNOLOGYT32GM008365 · NIGMS · UNIVERSITY OF IOWA · PI KERNS, ROBERT JOHN · 1990 to 2021
$3.8M
National Research Service Award Institutional Research Training Grants (T32)T32HL080070 · NHLBI · UNIVERSITY OF IOWA · PI O'DORISIO, M. SUE · 2005 to 2014
$1.5M
Polyacridine Peptide Mediated Gene TargetingR01GM097093 · NIGMS · UNIVERSITY OF IOWA · PI RICE, KEVIN G · 2011 to 2014
$1.1M
NHLBI NIH HHS T32HL080070NIGMS NIH HHS GM097093NIGMS NIH HHS T32GM008365
6 · The paper itself

Abstract

Two uptake mechanisms were identified for PEGylated DNA polyplex biodistribution to the liver. At a low polyplex dose, a rapid-uptake mechanism dominates, resulting in 60% capture by liver in 5 min, due to a saturable receptor-mediated process. Rapid-uptake led to the fast metabolism of polyplexes by liver (t1/2 = 2.1 h), correlating with a 1-μg pGL3 polyplex dose losing full transfection competency after 4 h in the liver. Dose escalation of either polyplex or poly(ethylene glycol) (PEG) peptide led to the saturation of rapid-uptake and revealed a delayed-uptake mechanism for polyplexes by liver. Delayed-uptake was characterized by the slower liver accumulation of 40% of the polyplex dose over 40 min, followed by slow metabolism (t1/2 = 15 h) and an extended time (12 h) for a 1-μg pGL3 polyplex dose, remaining fully transfection competent in the liver. The delayed-uptake mechanism is consistent with polyplexes crossing liver fenestrated endothelial cells to reach steady state in the space of Disse. The results describe how to control polyplex biodistribution to liver to avoid rapid-uptake and metabolism, in favor of delayed-uptake, to preserve polyplex transfection competency in the liver for up to 12 h.

Indexed as

AnimalsDNAEndothelial CellsGene ExpressionKupffer CellsLiverMicePlasmidsPolyethylene GlycolsTissue DistributionTransfectionDNAPolyethylene Glycols

Identifiers

PMID25253445
OpenAlexW2041925668

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.