Evidence map›Paper›PMID 19429866›Full record

ArticleBlood2009

Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer.

Raul Alba, Angela C Bradshaw, Alan L Parker, David Bhella, Simon N Waddington, Stuart A Nicklin, Nico van Rooijen, Jerome Custers, Jaap Goudsmit, Dan H Barouch and 2 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% 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

114 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.

  1. Pooled it
  2. Article
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  6. Article
  7. Molecular therapy. Methods & clinical development · 2025
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  10. Article
  11. Article
  12. Review
  13. Article
  14. Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Raul AlbaBritish Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, G12 8TA, UK.
Angela C Bradshaw
Alan L Parker
David Bhella
Simon N Waddington
Stuart A Nicklin
Nico van Rooijen
Jerome Custers
Jaap Goudsmit
Dan H Barouch
John H McVey
Andrew H Baker
British Heart Foundation · GBBeth Israel Deaconess Medical Center · USMedical Research Council · GBThe Royal Free Hospital · GBThrombosis Research Institute · GBVrije Universiteit Amsterdam · NL

Funding

Preclinical Evaluation of Novel Adenovirus Prime-Boost HIV-1 VaccineU19AI078526 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BAROUCH, DAN H. · 2008 to 2012
$44.0M
Preclinical Evaluation of Novel Adenovirus VectorsU19AI066305 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI GOUDSMIT, JAAP · 2005 to 2009
$19.8M
Novel Adenovirus Vaccine Vectors for HIV/SIVR01AI066924 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BAROUCH, DAN H. · 2006 to 2010
$3.5M
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_U130115834NIAID NIH HHS AI066305NIAID NIH HHS AI066924NIAID NIH HHS AI078526NIAID NIH HHS R01 AI066924NIAID NIH HHS U19 AI066305NIAID NIH HHS U19 AI078526
6 · The paper itself

Abstract

Recent studies have demonstrated the importance of coagulation factor X (FX) in adenovirus (Ad) serotype 5-mediated liver transduction in vivo. FX binds to the adenovirus hexon hypervariable regions (HVRs). Here, we perform a systematic analysis of FX binding to Ad5 HVRs 5 and 7, identifying domains and amino acids critical for this interaction. We constructed a model of the Ad5-FX interaction using crystallographic and cryo-electron microscopic data to identify contact points. Exchanging Ad5 HVR5 or HVR7 from Ad5 to Ad26 (which does not bind FX) diminished FX binding as analyzed by surface plasmon resonance, gene delivery in vitro, and liver transduction in vivo. Exchanging Ad5-HVR5 for Ad26-HVR5 produced deficient virus maturation. Importantly, defined mutagenesis of just 2 amino acids in Ad5-HVR5 circumvented this and was sufficient to block liver gene transfer. In addition, mutation of 4 amino acids in Ad5-HVR7 or a single mutation at position 451 also blocked FX-mediated effects in vitro and in vivo. We therefore define the regions and amino acids on the Ad5 hexon that bind with high affinity to FX thereby better defining adenovirus infectivity pathways. These vectors may be useful for gene therapy applications where evasion of liver transduction is a prerequisite.

Indexed as

Mutagenesis, Site-DirectedTransduction, GeneticAdenoviruses, HumanAmino Acid SequenceAnimalsBinding SitesCapsid ProteinsCell LineConserved SequenceCryoelectron MicroscopyCrystallography, X-RayFactor XGenetic VectorsHumansLiverMaleCapsid ProteinsFactor Xhexon capsid protein, AdenovirusRecombinant Fusion Proteins

Identifiers

PMID19429866
PMCPMC2721791
OpenAlexW1982651102

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.