Evidence map›Paper›PMID 22497875›Full record

ArticleVaccine2012

High-efficiency transduction of human monocyte-derived dendritic cells by capsid-modified recombinant AAV2 vectors.

George V Aslanidi, Angela E Rivers, Luis Ortiz, Lakshmanan Govindasamy, Chen Ling, Giridhara R Jayandharan, Sergei Zolotukhin, Mavis Agbandje-McKenna, Arun Srivastava

Open access · greenAbstract read
In one paragraph

Article in Vaccine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

36 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Capsid Modifications for Targeting and Improving the Efficacy of AAV Vectors.Molecular therapy. Methods & clinical development · 2019
    Review
  13. Article
  14. E2F-1 promotes DAPK2-induced anti-tumor immunity of gastric cancer cells by targeting miR-34a.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  15. Article
  16. Article
  17. Microglia-specific targeting by novel capsid-modified AAV6 vectors.Molecular therapy. Methods & clinical development · 2016
    Article
  18. Article
  19. Article
  20. Review
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

9 authors at 3 institutions in 2 countries.

George V AslanidiDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida, College of Medicine, Gainesville, FL, USA. aslanidi@peds.ufl.edu
Angela E Rivers
Luis Ortiz
Lakshmanan Govindasamy
Chen Ling
Giridhara R Jayandharan
Sergei Zolotukhin
Mavis Agbandje-McKenna
Arun Srivastava
Florida College · USUniversity of Florida · USChristian Medical College & Hospital · IN

Funding

VIRAL VECTOR DELIVERY OF ANTISENSE TO ACE MRNA IN CARDIOVASCULAR DISEASEP01HL059412 · NHLBI · UNIVERSITY OF FLORIDA · PI MUZYCZKA, NICHOLAS · 1998 to 2012
$20.2M
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
Structural studies of AAV capsids and their glycan receptor interactionsR01GM082946 · NIGMS · UNIVERSITY OF FLORIDA · PI ROBERT MCKENNA · 2007 to 2026
$6.1M
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
Development of AAV vectors for the phenotypic correction of sickle cell diseaseK01HL103172 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI RIVERS, ANGELA · 2010 to 2014
$697k
NCATS NIH HHS UL1 TR000064NHLBI NIH HHS K01 HL103172NHLBI NIH HHS P01 HL059412NHLBI NIH HHS R01 HL-097088NHLBI NIH HHS R01 HL097088NIDDK NIH HHS P01 DK058327NIGMS NIH HHS R01 GM-082946NIGMS NIH HHS R01 GM082946
6 · The paper itself

Abstract

Phosphorylation of surface-exposed tyrosine residues negatively impacts the transduction efficiency of recombinant AAV2 vectors. Pre-treatment of cells with specific cellular serine/threonine kinase inhibitors also significantly increased the transduction efficiency of AAV2 vectors. We reasoned that site-directed mutagenesis of surface-exposed serine residues might allow the vectors to evade phosphorylation and thus lead to higher transduction efficiency. Each of the 15 surface-exposed serine (S) residues was substituted with valine (V) residues, and the transduction efficiency of three of these mutants, S458V, S492V and S662V, was increased by up to ≈ 20-fold in different cell types. The S662V mutant was efficient in transducing human monocyte-derived dendritic cells (moDCs), a cell type not readily amenable to transduction by the conventional AAV vectors, and did not induce any phenotypic changes in these cells. Recombinant S662V-AAV2 vectors encoding a truncated human telomerase (hTERT) gene were generated and used to stimulate cytotoxic T cells (CTLs) against target cells. S662V-AAV2-hTERT vector-transduced DCs resulted in rapid, specific T-cell clone proliferation and generation of robust CTLs, which led to specific cell lysis of K562 cells. These studies suggest that high-efficiency transduction of moDCs by serine-modified AAV2 vectors is feasible, which supports the potential utility of these vectors for future human DCs vaccine studies.

Indexed as

Genetic VectorsTransduction, GeneticAdenoviruses, HumanAmino Acid SubstitutionCapsid ProteinsCells, CulturedDendritic CellsHumansMutagenesis, Site-DirectedMutant ProteinsSerineCapsid ProteinsMutant ProteinsSerine

Identifiers

PMID22497875
PMCPMC3356484
OpenAlexW1974237315

What OpenQuestion holds

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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.