Evidence map›Paper›PMID 15647765›Full record

ArticleGene therapy2005

PEGylated helper-dependent adenoviral vectors: highly efficient vectors with an enhanced safety profile.

M A Croyle, H T Le, K D Linse, V Cerullo, G Toietta, A Beaudet, L Pastore

Abstract read
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In one paragraph

Article in Gene therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

62 citing papers in PubMed, 112 citations in OpenAlex.

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  19. Integrin Receptors Play a Key Role in the Regulation of Hepatic CYP3A.Drug metabolism and disposition: the biological fate of chemicals · 2016
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2 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

7 authors at 4 institutions in 2 countries.

M A CroyleCollege of Pharmacy, Division of Pharmaceutics, The University of Texas at Austin, TX 78712, USA.
H T Le
K D Linse
V Cerullo
G Toietta
A Beaudet
L Pastore
The University of Texas at Austin · USBaylor College of Medicine · USCeinge Biotecnologie Avanzate (Italy) · ITUniversity of Naples Federico II · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transgene expression from helper-dependent adenoviral (HD-Ad) vectors is effective and long lasting, but not permanent. Their use is also limited by the host response against capsid proteins that precludes successful gene expression upon readministration. In this report, we test the hypothesis that PEGylation of HD-Ad reduces its toxicity and promotes transgene expression upon readministration. PEGylation did not compromise transduction efficiency in vitro and in vivo and reduced peak serum IL-6 levels two-fold. IL-12 and TNF-alpha levels were reduced three- and seven-fold, respectively. Thrombocytopenia was not detected in mice treated with the PEGylated vector. Serum transaminases were not significantly elevated in mice treated with either vector. Mice immunized with 1 x 10(11) particles of unmodified HD-Ad expressing human alpha-1 antitrypsin (hA1AT) were rechallenged 28 days later with 8 x 10(10) particles of unmodified or PEG-conjugated vector expressing beta-galactosidase. Trace levels of beta-galactosidase (52.23+/-19.2 pg/mg protein) were detected in liver homogenates of mice that received two doses of unmodified HD-Ad. Mice rechallenged with PEGylated HD-Ad produced significant levels of beta-galactosidase (5.1+/-0.4 x 10(5) pg/mg protein, P=0.0001). This suggests that PEGylation of HD-Ad vectors may be appropriate for their safe and efficient use in the clinic.

Indexed as

Polyethylene GlycolsAdenoviridaeAnimalsbeta-GalactosidaseChemical PhenomenaChemistry, PhysicalCytokinesDrug CarriersGene ExpressionGenetic VectorsLiverMaleMiceMice, Inbred C57BLPlatelet CountSurface Propertiesbeta-GalactosidaseCytokinesDrug Carriersmonomethoxypolyethylene glycolPolyethylene GlycolsTransaminases

Identifiers

PMID15647765
OpenAlexW1982794080

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.