Evidence map›Paper›PMID 21776025›Full record

ArticleGene therapy2012

Development of optimized AAV3 serotype vectors: mechanism of high-efficiency transduction of human liver cancer cells.

B Cheng, C Ling, Y Dai, Y Lu, L G Glushakova, S W Y Gee, K E McGoogan, G V Aslanidi, M Park, P W Stacpoole and 4 more

Abstract read
In one paragraph

Article in Gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.6field-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

35 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022
    Review
  5. Article
  6. Review
  7. Article
  8. Role of Essential Metal Ions in AAV Vector-Mediated Transduction.Molecular therapy. Methods & clinical development · 2020
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Adeno-associated virus (AAV) vectors in cancer gene therapy.Journal of controlled release : official journal of the Controlled Release Society · 2016
    Review
  17. Article
  18. Strategies to generate high-titer, high-potency recombinant AAV3 serotype vectors.Molecular therapy. Methods & clinical development · 2016
    Article
  19. Comparative Study of Liver Gene Transfer With AAV Vectors Based on Natural and Engineered AAV Capsids.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    Article
  20. Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    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

14 authors at 3 institutions in 2 countries.

B ChengDivision of Cellular and Molecular Therapy, Departments of Pediatics and Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610-3633, USA.
C Ling
Y Dai
Y Lu
L G Glushakova
S W Y Gee
K E McGoogan
G V Aslanidi
M Park
P W Stacpoole
D Siemann
C Liu
A Srivastava
C Ling
University of Florida · USFlorida College · USMcGill University · CA

Funding

UF Clinical and Translational Science AwardUL1TR000064 · NCATS · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2012 to 2014
$12.2M
Strategies for Sustained Effect of AAV-mediated Correction of Pompe DiseaseP01DK058327 · NIDDK · UNIVERSITY OF FLORIDA · PI CAMPBELL-THOMPSON, MARTHA · 2000 to 2009
$11.0M
Next Generation of Recombinant AAV Serotype Vectors for Gene TherapyR01HL097088 · NHLBI · UNIVERSITY OF FLORIDA · PI GAO, GUANGPING, HERZOG, ROLAND W. · 2010 to 2018
$5.4M
Human Parvovirus B19 Vectors: Mechanism of TransductionR01HL076901 · NHLBI · UNIVERSITY OF FLORIDA · PI SRIVASTAVA, ARUN · 2004 to 2008
$1.8M
NCATS NIH HHS UL1 TR000064NHLBI NIH HHS R01 HL-076901NHLBI NIH HHS R01 HL076901NHLBI NIH HHS R01 HL-097088NHLBI NIH HHS R01 HL097088NIDDK NIH HHS P01 DK-058327NIDDK NIH HHS P01 DK058327
6 · The paper itself

Abstract

Our recent studies have revealed that among the 10 different commonly used adeno-associated virus (AAV) serotypes, AAV3 vectors transduce human liver cancer cells extremely efficiently because these cells express high levels of human hepatocyte growth factor receptor (hHGFR), and AAV3 utilizes hHGFR as a cellular co-receptor for viral entry. In this report, we provide further evidence that both extracellular as well as intracellular kinase domains of hHGFR are involved in AAV3 vector entry and AAV3-mediated transgene expression. We also document that AAV3 vectors are targeted for degradation by the host cell proteasome machinery, and that site-directed mutagenesis of surface-exposed tyrosine (Y) to phenylalanine (F) residues on AAV3 capsids significantly improves the transduction efficiency of Y701F, Y705F and Y731F mutant AAV3 vectors. The transduction efficiency of the Y705+731F double-mutant vector is significantly higher than each of the single mutants in liver cancer cells in vitro. In immunodeficient mouse xenograft models, direct intratumoral injection of AAV3 vectors also led to high-efficiency transduction of human liver tumor cells in vivo. We also document here that the optimized tyrosine-mutant AAV3 vectors lead to increased transduction efficiency following both intratumoral and tail-vein injections in vivo. The optimized tyrosine-mutant AAV3 serotype vectors containing proapoptotic genes should prove useful for the potential gene therapy of human liver cancers.

Indexed as

Genetic VectorsTransduction, GeneticAnimalsBreast NeoplasmsCarcinoma, HepatocellularCell Line, TumorDependovirusFemaleHumansLiver NeoplasmsMiceMutagenesis, Site-DirectedProteasome InhibitorsProtein Structure, TertiaryProto-Oncogene Proteins c-metTransplantation, HeterologousProteasome InhibitorsProto-Oncogene Proteins c-metTyrosine

Identifiers

PMID21776025
PMCPMC3519243
OpenAlexW2041705668

What OpenQuestion holds

Textmetadata
LicenceTDM
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.