Evidence map›Paper›PMID 15113916›Full record

ArticleJournal of virology2004

Analysis of adenovirus sequestration in the liver, transduction of hepatic cells, and innate toxicity after injection of fiber-modified vectors.

Dmitry M Shayakhmetov, Zong-Yi Li, Shaoheng Ni, André Lieber

Abstract read
In one paragraph

Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
10.8field-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

95 citing papers in PubMed, 205 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. iPSC-hepatocyte organoids as a novel platform to predict AAV gene therapy efficacy.Molecular therapy. Methods & clinical development · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Generation of Adenovirus for In Vitro and In Vivo Studies of Hepatocytes.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  18. Article
  19. Article
  20. Sphingomyelin synthase related protein is a mammalian phosphatidylethanolamine phospholipase C.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021
    Article

35 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

4 authors at 2 institutions in 2 countries.

Dmitry M ShayakhmetovDivision of Medical Genetics, University of Washington, Seattle, WA 98195, USA.
Zong-Yi Li
Shaoheng Ni
André Lieber
Medical Genetics Center · DEUniversity of Washington · US

Funding

PILOT STUDY--RETROVIRUS MEDIATED TRANSFER OF HUMAN GLUCOCEREBROSIDASE GENEP30DK047754 · NIDDK · UNIVERSITY OF WASHINGTON · PI MILLER, ARTHUR DUSTY · 1994 to 2008
$8.4M
ONCOLYTIC ADENOVIRUSES FOR CERVICAL CANCER GENE THERAPYR01CA080192 · NCI · UNIVERSITY OF WASHINGTON · PI LIEBER, ANDRE MICHAEL · 1999 to 2009
$2.0M
NCI NIH HHS R01 CA080192NCI NIH HHS R01 CA 80192NHLBI NIH HHS HL 00008NIDDK NIH HHS P30 DK047754NIDDK NIH HHS P30 DK 47754
6 · The paper itself

Abstract

After intravenous administration, adenovirus (Ad) vectors are predominantly sequestered by the liver. Delineating the mechanisms for Ad accumulation in the liver is crucial for a better understanding of Ad clearance and Ad-associated innate toxicity. To help address these issues, in this study, we used Ad vectors with different fiber shaft lengths and either coxsackievirus-Ad receptor (CAR)-interacting Ad serotype 9 (Ad9) or non-CAR-interacting Ad35 fiber knob domains. We analyzed the kinetics of Ad vector accumulation in the liver, uptake into hepatocytes and Kupffer cells, and induction of cytokine expression and release in response to systemic vector application. Immediately after intravenous injection, all Ad vectors accumulated equally efficiently in the liver; however, only genomes of long-shafted Ads were maintained in the liver tissue over time. We found that Kupffer cell uptake of long-shafted Ads was mediated by the fiber knob domain and was CAR independent. The short-shafted Ads were unable to efficiently interact with hepatocellular receptors and were not taken up by Kupffer cells. Moreover, our studies indicated that Kupffer cells were not the major reservoir for the observed accumulation of Ads (used in this study) in the liver within the first 30 min after virus infusion. The lower level of liver cell transduction by short-shafted Ads correlated with a significantly reduced inflammatory anti-Ad response as well as liver damage induced by the systemic administration of these vectors. This study contributes to a better understanding of the biology of systemically applied Ad and will help in designing safer vectors that can efficiently transduce target tissues.

Indexed as

AdenoviridaeAlanine TransaminaseAnimalsCytokinesGenetic VectorsHepatocytesInterleukin-6Kupffer CellsLiverMiceMice, Inbred C57BLReceptors, VirusTumor Necrosis Factor-alphaAlanine TransaminaseCytokinesInterleukin-6Receptors, VirusTumor Necrosis Factor-alpha

Identifiers

PMID15113916
PMCPMC400378
OpenAlexW1966037150

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.