Evidence map›Paper›PMID 26527686›Full record

ArticleThe Journal of biological chemistry2016

Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction.

Garrett E Berry, Aravind Asokan

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  12. CRISPR Activation EnhancesMolecular therapy. Methods & clinical development · 2019
    Article
  13. Article
  14. An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs.Molecular therapy. Methods & clinical development · 2018
    Article
  15. Article
  16. Review
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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

2 authors at 2 institutions in 2 countries.

Garrett E BerryFrom the Gene Therapy Center, Department of Genetics, Curriculum in Genetics and Molecular Biology, and.
Aravind AsokanFrom the Gene Therapy Center, Department of Genetics, Department of Biochemistry and Biophysics, The University of North Carolina, Chapel Hill, North Carolina 27599-7352 aravind@med.unc.edu.
Gene Therapy Laboratory · FRUniversity of North Carolina at Chapel Hill · US

Funding

VECTOR AND MOLECULAR BIOLOGY COREP01HL112761 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SAMULSKI, RICHARD J · 2013 to 2017
$11.3M
Determinants of AAV TropismR01HL089221 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Aravind Asokan · 2009 to 2026
$8.1M
NRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9M
Linking DNA Replication Origin Licensing with Cell Cycle ProgressionF31CA165891 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COLEMAN, KATE E · 2013 to 2015
$85k
NHLBI NIH HHS P01 HL112761NHLBI NIH HHS P01HL112761NHLBI NIH HHS R01 HL089221NHLBI NIH HHS R01HL089221NIGMS NIH HHS 5T32GM007092NIGMS NIH HHS T32 GM007092
6 · The paper itself

Abstract

Intracellular trafficking of viruses can be influenced by a variety of inter-connected cellular sorting and degradation pathways involving endo-lysosomal vesicles, the ubiquitin-proteasome system, and autophagy-based or endoplasmic reticulum-associated machinery. In the case of recombinant adeno-associated viruses (AAV), proteasome inhibitors are known to prevent degradation of ubiquitinated AAV capsids, thereby leading to increased nuclear accumulation and transduction. However, the impact of other cellular degradation pathways on AAV trafficking is not well understood. In the current study, we screened a panel of small molecules focused on modulating different cellular degradation pathways and identified eeyarestatin I (EerI) as a novel reagent that enhances AAV transduction. EerI improved AAV transduction by an order of magnitude regardless of vector dose, genome architecture, cell type, or serotype. This effect was preceded by sequestration of AAV within enlarged vesicles that were dispersed throughout the cytoplasm. Specifically, EerI treatment redirected AAV particles toward large vesicles positive for late endosomal (Rab7) and lysosomal (LAMP1) markers. Notably, MG132 and EerI (proteasomal and endoplasmic reticulum-associated degradation inhibitors, respectively) appear to enhance AAV transduction by increasing the intracellular accumulation of viral particles in a mutually exclusive fashion. Taken together, our results expand on potential strategies to redirect recombinant AAV vectors toward more productive trafficking pathways by deregulating cellular degradation mechanisms.

Indexed as

EndocytosisTransduction, GeneticAnimalsCapsidCell Line, TumorChickensCytosolDependovirusEndosomesGenome, ViralHEK293 CellsHumansHydrazonesHydroxyureaLeupeptinsLysosomal-Associated Membrane Protein 11-(4-chlorophenyl)-3-(3-(4-chlorophenyl)-5,5-dimethyl-1-(3-(5-nitrofuran-2-yl)allyldienehydrazinocarbonylmethyl)-2-oxoimidazolidin-4-yl)-1-hydroxyureabenzyloxycarbonylleucyl-leucyl-leucine aldehydeHydrazonesHydroxyureaLAMP1 protein, humanLeupeptinsLysosomal-Associated Membrane Protein 1Lysosomal Membrane Proteinsrab7 GTP-Binding Proteinsrab7 GTP-binding proteins, humanrab GTP-Binding Proteinsadeno-associated virusconfocal microscopygene therapyintracellular traffickingproteasometransductionvesiclevirus

Identifiers

PMID26527686
PMCPMC4705411
OpenAlexW2226328347

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.