Evidence map›Paper›PMID 15215884›Full record

ArticleGene therapy2004

Extended plasma circulation time and decreased toxicity of polymer-coated adenovirus.

N K Green, C W Herbert, S J Hale, A B Hale, V Mautner, R Harkins, T Hermiston, K Ulbrich, K D Fisher, L W Seymour

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 202 citations in OpenAlex.

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32 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

N K GreenHybrid Systems Ltd, Oxford BioBusiness Centre, Littlemore Park, Littlemore, Oxford, UK.
C W Herbert
S J Hale
A B Hale
V Mautner
R Harkins
T Hermiston
K Ulbrich
K D Fisher
L W Seymour
University of Oxford · GBCzech Academy of Sciences, Institute of Macromolecular Chemistry · CZUniversity of Birmingham · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Systemic delivery of adenoviral vectors is a major goal in cancer gene therapy, but is currently prohibited by rapid hepatic uptake of virus following intravenous injection with levels of viable virus in the murine plasma typically falling to less than 0.1% after 30 min. We have used a surface-masking technique based on multivalent copolymers of poly(N-(2-hydroxypropyl)methacrylamide) to ablate all pathways of receptor-mediated infection, combined with dose modulation to achieve partial saturation of nonspecific uptake pathways. Polymer coating gave at least 100-fold decreased hepatic transgene expression at all doses and even high doses of coated virus (pc-virus) showed no weight loss or stimulation of serum transaminases. Low doses of virus and pc-virus (10(9) viral particles (vp)/mouse) were mainly captured by the liver (assessed by quantitative PCR), although higher doses led to greater fractional persistence in the plasma (measured after 30 min). Coated virus at a dose of 6 x 10(11) vp/mouse showed nearly 50% plasma circulation, representing a 3.5-fold greater area under the concentration-time curve (0-30 min) compared to unmodified virus. Such an increase in the bioavailability of adenovirus, coupled with substantial decreases in toxicity and unwanted transgene expression is an important step towards producing systemically available tumour-targeted viruses.

Indexed as

AdenoviridaePolymersAnimalsGene ExpressionGene TargetingGenetic TherapyGenetic VectorsInjections, IntravenousLiverMiceNeoplasmsPhagocytosisPlasmaReceptors, VirusRecombination, GeneticTransduction, GeneticPolymersReceptors, Virus

Identifiers

PMID15215884
OpenAlexW2079852426

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.