Evidence map›Paper›PMID 14645549›Full record

ArticleJournal of virology2003

Targeting of adenovirus via genetic modification of the viral capsid combined with a protein bridge.

Nikolay Korokhov, Galina Mikheeva, Alexander Krendelshchikov, Natalya Belousova, Vera Simonenko, Valentina Krendelshchikova, Alexander Pereboev, Alexander Kotov, Olga Kotova, Pierre L Triozzi and 7 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.7field-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

30 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
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  8. Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters.Proceedings of the National Academy of Sciences of the United States of America · 2013
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  13. Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins.Journal of controlled release : official journal of the Controlled Release Society · 2011
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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

17 authors at 3 institutions in 2 countries.

Nikolay KorokhovVectorLogics, Inc., Alabama 35294, USA.
Galina Mikheeva
Alexander Krendelshchikov
Natalya Belousova
Vera Simonenko
Valentina Krendelshchikova
Alexander Pereboev
Alexander Kotov
Olga Kotova
Pierre L Triozzi
Wayne A Aldrich
Joanne T Douglas
Kin-Ming Lo
Papia T Banerjee
Stephen D Gillies
David T Curiel
Victor Krasnykh
Gene Therapy Laboratory · FRU-M Rogel Cancer CenterUniversity of Alabama at Birmingham · US

Funding

UAB Rexinoids for Breast Cancer PreventionP50CA089019 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GRIZZLE, WILLIAM E. · 2000 to 2011
$26.0M
DENDRITIC CELL SPECIFIC VECTORR01CA086881 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CURIEL, DAVID TERRY · 2000 to 2004
$1.1M
Derivation of Dendritic Cell-Specific Adenovirus VectorsR41CA091608 · NCI · VECTORLOGICS, INC. · PI KRASNYKH, VICTOR · 2001 to 2001
$100k
NCI NIH HHS 1R41CA 91608-01NCI NIH HHS P50 CA089019NCI NIH HHS P50 CA89019NCI NIH HHS R01 CA086881NCI NIH HHS R01 CA86881
6 · The paper itself

Abstract

A potential barrier to the development of genetically targeted adenovirus (Ad) vectors for cell-specific delivery of gene therapeutics lies in the fact that several types of targeting protein ligands require posttranslational modifications, such as the formation of disulfide bonds, which are not available to Ad capsid proteins due to their nuclear localization during assembly of the virion. To overcome this problem, we developed a new targeting strategy, which combines genetic modifications of the Ad capsid with a protein bridge approach, resulting in a vector-ligand targeting complex. The components of the complex associate by virtue of genetic modifications to both the Ad capsid and the targeting ligand. One component of this mechanism of association, the Fc-binding domain of Staphylococcus aureus protein A, is genetically incorporated into the Ad fiber protein. The ligand is comprised of a targeting component fused with the Fc domain of immunoglobulin, which serves as a docking moiety to bind to these genetically modified fibers during the formation of the Ad-ligand complex. The modular design of the ligand solves the problem of structural and biosynthetic compatibility with the Ad and thus facilitates targeting of the vector to a variety of cellular receptors. Our study shows that targeting ligands incorporating the Fc domain and either an anti-CD40 single-chain antibody or CD40L form stable complexes with protein A-modified Ad vectors, resulting in significant augmentation of gene delivery to CD40-positive target cells. Since this gene transfer is independent of the expression of the native Ad5 receptor by the target cells, this strategy results in the derivation of truly targeted Ad vectors suitable for tissue-specific gene therapy.

Indexed as

Gene TargetingGenetic VectorsAdenoviruses, HumanCapsid ProteinsCD40 AntigensCell LineDisulfidesGenetic EngineeringGene Transfer TechniquesHumansImmunoglobulin FragmentsLigandsRecombinant ProteinsStaphylococcal Protein ATransduction, GeneticCapsid ProteinsCD40 AntigensDisulfideshexon capsid protein, AdenovirusImmunoglobulin FragmentsLigandsRecombinant ProteinsStaphylococcal Protein A

Identifiers

PMID14645549
PMCPMC296051
OpenAlexW2147393870

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.