Evidence map›Paper›PMID 20511542›Full record

ArticleBlood2010

Adenovirus capsid-display of the retro-oriented human complement inhibitor DAF reduces Ad vector-triggered immune responses in vitro and in vivo.

Sergey S Seregin, Yasser A Aldhamen, Daniel M Appledorn, Zachary C Hartman, Nathaniel J Schuldt, Jeannine Scott, Sarah Godbehere, Haixiang Jiang, Michael M Frank, Andrea Amalfitano

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Immunology of Adenoviral Vectors in Cancer Therapy.Molecular therapy. Methods & clinical development · 2019
    Review
  8. Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018
    Article
  9. Article
  10. Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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 2 institutions in 1 country.

Sergey S SereginDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48823, USA.
Yasser A Aldhamen
Daniel M Appledorn
Zachary C Hartman
Nathaniel J Schuldt
Jeannine Scott
Sarah Godbehere
Haixiang Jiang
Michael M Frank
Andrea Amalfitano
Michigan State University · USDuke Medical Center · US

Funding

RNA TRASFECTED DENDRITIC CELLS FOR CANCER IMMUNOTHERAPYP01CA078673 · NCI · DUKE UNIVERSITY · PI MORSE, MICHAEL A · 1999 to 2008
$13.2M
Adenovirus vectors and complement systemR01DK069884 · NIDDK · MICHIGAN STATE UNIVERSITY · PI AMALFITANO, ANDREA NA · 2005 to 2007
$775k
NCI NIH HHS P01 CA078673NIDDK NIH HHS R01 DK069884NIDDK NIH HHS R01DK-069884
6 · The paper itself

Abstract

Adenovirus (Ad) vectors are widely used in human clinical trials. However, at higher dosages, Ad vector-triggered innate toxicities remain a major obstacle to many applications. Ad interactions with the complement system significantly contribute to innate immune responses in several models of Ad-mediated gene transfer. We constructed a novel class of Ad vectors, genetically engineered to "capsid-display" native and retro-oriented versions of the human complement inhibitor decay-accelerating factor (DAF), as a fusion protein from the C-terminus of the Ad capsid protein IX. In contrast to conventional Ad vectors, DAF-displaying Ads dramatically minimized complement activation in vitro and complement-dependent immune responses in vivo. DAF-displaying Ads did not trigger thrombocytopenia, minimized endothelial cell activation, and had diminished inductions of proinflammatory cytokine and chemokine responses. The retro-oriented display of DAF facilitated the greatest improvements in vivo, with diminished activation of innate immune cells, such as dendritic and natural killer cells. In conclusion, Ad vectors can capsid-display proteins in a manner that not only retains the functionality of the displayed proteins but also potentially can be harnessed to improve the efficacy of this important gene transfer platform for numerous gene transfer applications.

Indexed as

AdenoviridaeAmino Acid SequenceAnimalsBase SequenceCapsid ProteinsCD55 AntigensComplement ActivationComplement C3Dendritic CellsFlow CytometryGreen Fluorescent ProteinsHumansImmunity, InnateInflammation MediatorsLiverMiceCapsid ProteinsCD55 AntigensComplement C3Green Fluorescent ProteinsInflammation MediatorsRecombinant Fusion Proteins

Identifiers

PMID20511542
PMCPMC2947391
OpenAlexW1965001360

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.