Evidence map›Paper›PMID 26942476›Full record

ArticleHuman gene therapy2016

Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction.

Ping-Jie Xiao, Angela M Mitchell, Lu Huang, Chengwen Li, R Jude Samulski

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Myospreader improves gene editing in skeletal muscle by myonuclear propagation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. 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.

Ping-Jie Xiao1 Gene Therapy Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
Angela M Mitchell1 Gene Therapy Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
Lu Huang4 Department of Statistics, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
Chengwen Li1 Gene Therapy Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
R Jude Samulski1 Gene Therapy Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
VECTOR AND MOLECULAR BIOLOGY COREP01HL112761 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MONAHAN, PAUL E · 2013 to 2017
$11.3M
Rational and Combinatorial Engineering of AAV VectorsR01AI072176 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HIRSCH, MATTHEW LOUIS, SAMULSKI, RICHARD J · 2008 to 2017
$3.7M
AAV Gene Therapy for AAT DeficiencyR01DK084033 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LI, CHENGWEN · 2009 to 2016
$2.2M
Overcoming our clinical complications: AAV vector design for the treatment of DMDR01AR064369 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HIRSCH, MATTHEW LOUIS, SAMULSKI, RICHARD J · 2013 to 2017
$1.6M
NCI NIH HHS P30 CA016086NHLBI NIH HHS P01HL112761NIAID NIH HHS R01 AI072176NIAID NIH HHS R01AI072176NIAMS NIH HHS R01AR064369NIDDK NIH HHS R01DK084033
6 · The paper itself

Abstract

Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion.

Indexed as

Transduction, GeneticVirus InternalizationAnimalsCell Cycle CheckpointsCell NucleusDependovirusGenetic VectorsHEK293 CellsHeLa CellsHumansMice, Inbred BALB CMice, SCIDMicrotubule-Organizing CenterMicrotubulesNocodazolePromoter Regions, GeneticNocodazole

Identifiers

PMID26942476
PMCPMC4841008
OpenAlexW2336758640

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.