Evidence map›Paper›PMID 21574868›Full record

ArticleHuman gene therapy2011

Unique characteristics of AAV1, 2, and 5 viral entry, intracellular trafficking, and nuclear import define transduction efficiency in HeLa cells.

Nicholas W Keiser, Ziying Yan, Yulong Zhang, Diana C M Lei-Butters, John F Engelhardt

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

26 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Emerging Technologies for Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018
    Article
  14. Article
  15. Article
  16. Riding the R Train into the Cell.PLoS pathogens · 2015
    Review
  17. 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

5 authors at 1 institution in 1 country.

Nicholas W KeiserDepartment of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Ziying Yan
Yulong Zhang
Diana C M Lei-Butters
John F Engelhardt
University of Iowa · US

Funding

Vector Core-Core 2P30DK054759 · NIDDK · UNIVERSITY OF IOWA · PI Alejandro Antonio Pezzulo · 1998 to 2026
$30.5M
MECHANISMS OF RAAV TRANSDUCTION IN THE AIRWAYR01HL058340 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ENGELHARDT, JOHN F · 1996 to 2008
$3.0M
rAAV-directed gene therapy to the lung in cystic fibrosis ferret modelsR01HL108902 · NHLBI · UNIVERSITY OF IOWA · PI ENGELHARDT, JOHN F · 2011 to 2014
$2.2M
NHLBI NIH HHS HL058340NHLBI NIH HHS HL108902NHLBI NIH HHS R01 HL108902NIDDK NIH HHS P30 DK054759
6 · The paper itself

Abstract

Biological differences between recombinant adeno-associated virus (rAAV) serotypes define their efficiencies in expressing a transgene in a particular target cell. Few studies have directly compared how differences in viral entry, intracellular trafficking, and nuclear import of rAAV serotypes influence the effectiveness of transduction in the same cell type. We evaluated these characteristics for three rAAV serotypes in HeLa cells, using biochemical techniques and fluorescence-based detection of multiple serotypes in the same cell. Although rAAV2 exhibited the slowest entry, intracellular trafficking, and nuclear import among the three serotypes, it elicited the highest levels of transduction. Conversely, rAAV1 exhibited more rapid entry and nuclear import than the other serotypes, yet was ineffective at transducing HeLa cells due to impaired capsid disassembly in the nucleus. rAAV5, which entered the cell less rapidly than rAAV1, was imported efficiently into the nucleus, but then rapidly degraded, resulting in poor transduction of HeLa cells. We conclude that rAAV1, 2, and 5 utilize distinct mechanisms for intracellular trafficking, and that post-nuclear events play an important role in determining the efficiency of HeLa cell transduction by these serotypes. Thus, overcoming post-nuclear barriers that limit uncoating and/or promote virion degradation may enhance the efficiency of certain AAV serotypes.

Indexed as

Transduction, GeneticActive Transport, Cell NucleusCell MembraneCell NucleusDependovirusGenetic VectorsHeLa CellsHumans

Identifiers

PMID21574868
PMCPMC3225038
OpenAlexW2044291926

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.