Evidence map›Paper›PMID 19603000›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009

Influence of coagulation factor x on in vitro and in vivo gene delivery by adenovirus (Ad) 5, Ad35, and chimeric Ad5/Ad35 vectors.

Jenny A Greig, Suzanne Mk Buckley, Simon N Waddington, Alan L Parker, David Bhella, Rebecca Pink, Ahad A Rahim, Takashi Morita, Stuart A Nicklin, John H McVey and 1 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
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  5. Interactions of viruses and the humoral innate immune response.Clinical immunology (Orlando, Fla.) · 2020
    Review
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

11 authors at 6 institutions in 2 countries.

Jenny A GreigBritish Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
Suzanne Mk Buckley
Simon N Waddington
Alan L Parker
David Bhella
Rebecca Pink
Ahad A Rahim
Takashi Morita
Stuart A Nicklin
John H McVey
Andrew H Baker
British Heart Foundation · GBThe Royal Free Hospital · GBUniversity of Glasgow · GBMeiji Pharmaceutical University · JPThrombosis Research Institute · GBUniversity College London · GB

Funding

Biotechnology and Biological Sciences Research Council BB/E021301/1Biotechnology and Biological Sciences Research Council BB/E02145X/1Biotechnology and Biological Sciences Research Council BB/E02145X/2British Heart FoundationMedical Research Council MC_U130115834
6 · The paper itself

Abstract

The binding of coagulation factor X (FX) to the hexon of adenovirus (Ad) 5 is pivotal for hepatocyte transduction. However, vectors based on Ad35, a subspecies B Ad, are in development for cancer gene therapy, as Ad35 utilizes CD46 (which is upregulated in many cancers) for transduction. We investigated whether interaction of Ad35 with FX influenced vector tropism using Ad5, Ad35, and Ad5/Ad35 chimeras: Ad5/fiber(f)35, Ad5/penton(p)35/f35, and Ad35/f5. Surface plasmon resonance (SPR) revealed that Ad35 and Ad35/f5 bound FX with approximately tenfold lower affinities than Ad5 hexon-containing viruses, and electron cryomicroscopy (cryo-EM) demonstrated a direct Ad35 hexon:FX interaction. The presence of physiological levels of FX significantly inhibited transduction of vectors containing Ad35 fibers (Ad5/f35, Ad5/p35/f35, and Ad35) in CD46-positive cells. Vectors were intravenously administered to CD46 transgenic mice in the presence and absence of FX-binding protein (X-bp), resulting in reduced liver accumulation for all vectors. Moreover, Ad5/f35 and Ad5/p35/f35 efficiently accumulated in the lung, whereas Ad5 demonstrated poor lung targeting. Additionally, X-bp significantly reduced lung genome accumulation for Ad5/f35 and Ad5/p35/f35, whereas Ad35 was significantly enhanced. In summary, vectors based on the full Ad35 serotype will be useful vectors for selective gene transfer via CD46 due to a weaker FX interaction compared to Ad5.

Indexed as

AdenoviridaeAnimalsCell LineCHO CellsCricetinaeCricetulusCryoelectron MicroscopyFactor XGenetic VectorsHumansMembrane Cofactor ProteinMiceMice, TransgenicTransduction, GeneticFactor XMembrane Cofactor Protein

Identifiers

PMID19603000
PMCPMC2835023
OpenAlexW2114233076

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.