Evidence map›Paper›PMID 15331734›Full record

ArticleJournal of virology2004

Genome size and structure determine efficiency of postinternalization steps and gene transfer of capsid-modified adenovirus vectors in a cell-type-specific manner.

Dmitry M Shayakhmetov, Zong-Yi Li, Anuj Gaggar, Helen Gharwan, Vladimir Ternovoi, Volker Sandig, André Lieber

Open access · greenAbstract 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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Developing the next-generation of adenoviral vector vaccines.Human vaccines & immunotherapeutics · 2025
    Review
  3. Review
  4. HDAd6/35++ - A new helper-dependent adenovirus vector platform forMolecular therapy. Methods & clinical development · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Adenovirus virion stability and the viral genome: size matters.Molecular therapy : the journal of the American Society of Gene Therapy · 2009
    Article
  16. Article
  17. Article
  18. Article
  19. Article
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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 2 institutions in 2 countries.

Dmitry M ShayakhmetovDivision of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA.
Zong-Yi Li
Anuj Gaggar
Helen Gharwan
Vladimir Ternovoi
Volker Sandig
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 CA80192NHLBI NIH HHS HL-00-008NIDDK NIH HHS P30 DK047754NIDDK NIH HHS P30 DK47754
6 · The paper itself

Abstract

Adenovirus serotype 5 (Ad5) vectors containing Ad B-group fibers have become increasingly popular as gene transfer vectors because they efficiently transduce human cell types that are relatively refractory to Ad5 infection. So far, most B-group fiber-containing vectors have been first-generation vectors, deleted of E1 and/or E3 genes. Transduction with these vectors, however, results in viral gene expression and is associated with cytotoxicity and immune responses against transduced cells. To circumvent these problems, we developed fiber-chimeric Ad vectors devoid of all viral genes that were produced either by the homologous recombination of first-generation vectors or by using the Cre/lox-based helper virus system. In this study we compared early steps of infection between first-generation (35-kb genome) and Ad vectors devoid of all viral genes with genome sizes of 28 kb and 12.6 kb. All vectors possessed an Ad35-derived fiber knob domain, which uses CD46 as a primary attachment receptor. Using immortalized human hematopoietic cell lines and primary human CD34-positive hematopoietic cells, we found that the Ad genome size did not affect the efficiency of virus attachment to and internalization into cells. Furthermore, independently of the genome length and structure, all vectors migrated to the nucleus through late endosomal and lysosomal cellular compartments. However, the vector containing the short 12.6-kb genome was unable to efficiently escape from endosomes and deliver its DNA into the nucleus. Moreover, compared to other vectors, these Ad particles were less stable and had an abnormal capsid protein composition, including a lack of capsid-stabilizing protein IX. Our data indicate that the size and structure of the packaged viral genomes can affect the integrity of Ad particles, which in turn results in lower infectivity of Ad vectors.

Indexed as

Genome, ViralActive Transport, Cell NucleusAdenoviruses, HumanCapsid ProteinsCell LineDNA, ViralEndosomesGenetic VectorsGene Transfer TechniquesGreen Fluorescent ProteinsHumansLuminescent ProteinsMicroscopy, ElectronRecombinant ProteinsCapsid ProteinsDNA, ViralGreen Fluorescent ProteinsLuminescent ProteinsRecombinant Proteins

Identifiers

PMID15331734
PMCPMC514985
OpenAlexW2018932621

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.