Evidence map›Paper›PMID 9811719›Full record

ArticleJournal of virology1998

Adeno-associated virus type 2-mediated gene transfer: role of epidermal growth factor receptor protein tyrosine kinase in transgene expression.

C Mah, K Qing, B Khuntirat, S Ponnazhagan, X S Wang, D M Kube, M C Yoder, A Srivastava

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

50 citing papers in PubMed, 102 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Article
  6. Review
  7. Review
  8. Best of most possible worlds: Hybrid gene therapy vectors based on parvoviruses and heterologous viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Capsid Modifications for Targeting and Improving the Efficacy of AAV Vectors.Molecular therapy. Methods & clinical development · 2019
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  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

8 authors at 2 institutions in 1 country.

C MahDepartment of Microbiology and Immunology, Indianapolis, Indiana 46202, USA.
K Qing
B Khuntirat
S Ponnazhagan
X S Wang
D M Kube
M C Yoder
A Srivastava
Walther Cancer Foundation · USIndiana University School of Medicine

Funding

VectorP01HL053586 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI CLAPP, DAVID W · 1995 to 2009
$16.0M
PILOT AND FEASIBILITY STUDIESP30DK049218 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SROUR, EDWARD F · 1999 to 2004
$4.6M
PARVOVIRUS VECTORS FOR HUMAN GENE THERAPYR01HL058881 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SRIVASTAVA, ARUN · 1997 to 2002
$1.2M
GENETIC MODIFICATION/ALTERNATIVE SOURCES OF STEM CELLP50DK049218 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI LIECHTY, EDWARD A · 1994 to 1998
–
PARVOVIRUS-MEDIATED GENE TRANSFER IN STEM CELLSR01HL048342 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SRIVASTAVA, ARUN · 1992 to 1996
–
NHLBI NIH HHS HL-48342NHLBI NIH HHS HL-53586NHLBI NIH HHS HL-58881NHLBI NIH HHS P01 HL053586NHLBI NIH HHS R01 HL058881NIDDK NIH HHS P30 DK049218NIDDK NIH HHS P50 DK049218
6 · The paper itself

Abstract

Adeno-associated virus type 2 (AAV), a single-stranded, DNA-containing, nonpathogenic human parvovirus, has gained attention as a potentially useful vector for human gene therapy. However, the transduction efficiency of AAV vectors varies greatly in different cells and tissues in vitro and in vivo. We have recently documented that a cellular tyrosine phosphoprotein, designated the single-stranded D-sequence-binding protein (ssD-BP), plays an important role in AAV-mediated transgene expression (K. Y. Qing et al., Proc. Natl. Acad. Sci. USA 94:10879-10884, 1997) and that a strong correlation exists between the phosphorylation state of the ssD-BP and AAV transduction efficiency in vitro as well as in vivo (K. Y. Qing et al., J. Virol. 72:1593-1599, 1998). In this report, we document that treatment of cells with specific inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK) activity, such as tyrphostin, leads to significant augmentation of AAV transduction efficiency, and phosphorylation of the ssD-BP is mediated by the EGF-R PTK. Treatment of cells with EGF results in phosphorylation of the ssD-BP, whereas treatment with tyrphostin causes dephosphorylation of the ssD-BP and consequently leads to increased expression of the transgene. Furthermore, AAV transduction efficiency inversely correlates with expression of the EGF-R in different cell types, and stable transfection of the EGF-R cDNA causes phosphorylation of the ssD-BP, leading to significant inhibition in AAV-mediated transgene expression which can be overcome by the tyrphostin treatment. These data suggest that the PTK activity of the EGF-R is a crucial determinant in the life cycle of AAV and that further studies on the interaction between the EGF-R and the ssD-BP may yield new insights not only into its role in the host cell but also in the successful use of AAV vectors in human gene therapy.

Indexed as

Gene ExpressionGene Transfer TechniquesCell LineDependovirusDNA-Binding ProteinsDNA, ComplementaryEnzyme InhibitorsErbB ReceptorsGenetic TherapyGenisteinHumansHydroxyureaPhosphorylationTransduction, GeneticTyrphostinsDNA-Binding ProteinsDNA, ComplementaryEnzyme InhibitorsErbB ReceptorsGenisteinHydroxyureaTyrphostins

Identifiers

PMID9811719
PMCPMC110495
OpenAlexW2152187442

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.