Evidence map›Paper›PMID 12438615›Full record

ArticleJournal of virology2002

Conjugate-based targeting of recombinant adeno-associated virus type 2 vectors by using avidin-linked ligands.

Selvarangan Ponnazhagan, Gandham Mahendra, Sanjay Kumar, John A Thompson, Mark Castillas

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 130 citations in OpenAlex.

  1. Review
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  12. Review
  13. Nanobody-Enhanced Targeting of AAV Gene Therapy Vectors.Molecular therapy. Methods & clinical development · 2019
    Article
  14. Physical, chemical, and synthetic virology: Reprogramming viruses as controllable nanodevices.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2019
    Review
  15. 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

5 authors at 1 institution in 1 country.

Selvarangan PonnazhaganDepartment of Pathology, LHRB 513, The University of Alabama at Birmingham, 701 19th Street South, Birmingham, AL 35294, USA. sponnazh@path.uab.edu
Gandham Mahendra
Sanjay Kumar
John A Thompson
Mark Castillas
University of Alabama at Birmingham · US

Funding

UAB Core Center for Musculoskeletal DisordersP30AR046031 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ZAYZAFOON, MAJD · 2001 to 2010
$5.6M
MOLECULAR MECHANISMS OF ANGIOGENESISR01HL045990 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI THOMPSON, JOHN ANTHONY · 1993 to 2006
$1.8M
Viral and Host Proteins as Therapeutic TargetsZ01BC010494 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LE GRICE, STUART F. J. · 2003 to 2008
$1.0M
Novel dendritic cell therapy for human cancersR01CA090850 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2002 to 2005
$954k
SUPPRESSION OF TUMORIGENICITY IN HUMAN BREAST CELLSF32CA008359 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI YASWEN, PAUL I · 1987 to 1990
–
Intramural NIH HHS Z01 BC010494NCI NIH HHS 5P50 CA 8359NCI NIH HHS R01 CA090850NCI NIH HHS R01 CA 90850NHLBI NIH HHS R01 HL045990NHLBI NIH HHS R01 HL 45990NIAMS NIH HHS 1P30 AR 46031NIAMS NIH HHS P30 AR046031
6 · The paper itself

Abstract

The development of targeted vectors, capable of tissue-specific transduction, remains one of the important aspects of vector modification for gene therapy applications. Recombinant adeno-associated virus type 2 (rAAV-2)-based vectors are nonpathogenic, have relatively low immunogenicity, and are capable of long-term transgene expression. AAV-2 vectors bind primarily to heparan sulfate proteoglycan (HSPG), a receptor that is present in many tissues and cell types. Because of the widespread expression of HSPG on many tissues, targeted transduction in vivo appears to be limited with AAV-2 vectors. Thus, development of strategies to achieve transductional targeting will have a profound benefit in the future application of these vectors. We report here a novel conjugate-based targeting method to enhance tissue-specific transduction of AAV-2-based vectors. The present report utilized a high-affinity biotin-avidin interaction as a molecular bridge to cross-link purified targeting ligands, produced genetically as fusion proteins to core-streptavidin, in a prokaryotic expression system. Conjugation of the bispecific targeting protein to the vector was achieved by biotinylating purified rAAV-2 without abolishing the capsid structure, internalization, and subsequent transgene expression. The tropism-modified vectors, targeted via epidermal growth factor receptor (EGFR) or fibroblast growth factor 1alpha receptor (FGFR1alpha), resulted in a significant increase in transduction efficiency of EGFR-positive SKOV3.ip1 cells and FGFR1alpha-positive M07e cells, respectively. Further optimization of this method of targeting should enhance the potential of AAV-2 vectors in ex vivo and in vivo gene therapy and may form the basis for developing targeting methods for other AAV serotype capsids.

Indexed as

Recombination, GeneticBiotinylationCell LineDependovirusErbB ReceptorsGenetic TherapyGenetic VectorsHeparan Sulfate ProteoglycansHumansLigandsReceptor, Fibroblast Growth Factor, Type 1Receptor Protein-Tyrosine KinasesReceptors, Fibroblast Growth FactorStreptavidinTransduction, GeneticErbB ReceptorsFGFR1 protein, humanHeparan Sulfate ProteoglycansLigandsReceptor, Fibroblast Growth Factor, Type 1Receptor Protein-Tyrosine KinasesReceptors, Fibroblast Growth FactorStreptavidin

Identifiers

PMID12438615
PMCPMC136730
OpenAlexW2134124671

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.