Evidence map›Paper›PMID 26665132›Full record

ArticleMolecular therapy. Methods & clinical development2015

Super-resolution imaging of nuclear import of adeno-associated virus in live cells.

Joseph M Kelich, Jiong Ma, Biao Dong, Qizhao Wang, Mario Chin, Connor M Magura, Weidong Xiao, Weidong Yang

Abstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
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

45 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Casein kinase 2 activity is a host restriction factor for AAV transduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  16. Article
  17. Review
  18. Review
  19. Review
  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

8 authors.

Joseph M KelichDepartment of Biology, Temple University , Philadelphia, Pennsylvania, USA.
Jiong MaDepartment of Biology, Temple University , Philadelphia, Pennsylvania, USA.
Biao DongDepartment of Microbiology and Immunology, School of Medicine, Temple University , Philadelphia, Pennsylvania, USA.
Qizhao WangDepartment of Microbiology and Immunology, School of Medicine, Temple University , Philadelphia, Pennsylvania, USA.
Mario ChinDepartment of Microbiology and Immunology, School of Medicine, Temple University , Philadelphia, Pennsylvania, USA.
Connor M MaguraDepartment of Biology, Temple University , Philadelphia, Pennsylvania, USA.
Weidong XiaoDepartment of Microbiology and Immunology, School of Medicine, Temple University , Philadelphia, Pennsylvania, USA.
Weidong YangDepartment of Biology, Temple University , Philadelphia, Pennsylvania, USA.

Funding

Molecular Biology of Recombinant AAV GenomesR01HL080789 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAO, WEIDONG · 2006 to 2014
$3.1M
Novel adeno-associated virus vector production system developmentR01HL114152 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAO, WEIDONG · 2012 to 2016
$2.2M
Structure and Function of the Ciliary Pore ComplexR01GM116204 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VERHEY, KRISTEN J., YANG, WEIDONG · 2015 to 2018
$2.1M
Development of highly efficient factor VIII mini-gene therapyR01HL130871 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAO, WEIDONG · 2016 to 2019
$1.9M
Molecular engineering of factor VIII gene for rAAV deliveryR01HL084381 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI XIAO, WEIDONG · 2008 to 2012
$1.9M
Three-Dimensional Super-Resolution Microscopy Study of Nuclear TransportR01GM097037 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, WEIDONG · 2011 to 2015
$1.3M
Single-Molecule Three-Dimensional Snapshots of Nuclear TransportR15GM094041 · NIGMS · BOWLING GREEN STATE UNIVERSITY · PI YANG, WEIDONG · 2010 to 2010
$348k
NHLBI NIH HHS R01 HL080789NHLBI NIH HHS R01 HL084381NHLBI NIH HHS R01 HL114152NIGMS NIH HHS R01 GM097037NIGMS NIH HHS R01 GM116204NIGMS NIH HHS R15 GM094041
6 · The paper itself

Abstract

Adeno-associated virus (AAV) has been developed as a promising human gene therapy vector. Particularly, recombinant AAV vector (rAAV) achieves its transduction of host cells by crossing at least three physiological barriers including plasma membrane, endosomal membrane, and nuclear envelope (NE). So far, the AAV transduction mechanism has not been explored thoroughly at the single viral particle level. In this study, we employed high-speed super-resolution single-point edge-excitation sub-diffraction (SPEED) microscopy to map the events of single rAAV2 particles infecting live human cells with an unprecedented spatiotemporal resolution of 9-12 nm and 2-20 ms. Data reveal that rAAV2 particles are imported through nuclear pore complexes (NPCs) rather than nuclear membrane budding into the nucleus. Moreover, approximately 17% of the rAAV2 molecules starting from the cytoplasm successfully transverse the NPCs to reach the nucleoplasm, revealing that the NPCs act as a strict selective step for AAV delivery. This study lastly suggests a new pathway to improve AAV vectors for human gene therapy.

Identifiers

PMID26665132
PMCPMC4667716

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Registered trials

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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.