Evidence map›Paper›PMID 29116194›Full record

ArticleScientific reports2017

Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome.

Jayanth S Chandran, Paul S Sharp, Evangelia Karyka, João Miguel da Conceição Aves-Cruzeiro, Ian Coldicott, Lydia Castelli, Guillaume Hautbergue, Mark O Collins, Mimoun Azzouz

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
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  4. Casein kinase 2 activity is a host restriction factor for AAV transduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
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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

9 authors at 1 institution in 1 country.

Jayanth S ChandranDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK.
Paul S SharpDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK.
Evangelia KarykaDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK.
João Miguel da Conceição Aves-CruzeiroDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK.
Ian ColdicottDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK.
Lydia CastelliDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK.
Guillaume HautbergueDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK.ORCID 0000-0002-1621-261X
Mark O CollinsDepartment of Biomedical Science, The University of Sheffield, Sheffield, UK.ORCID 0000-0002-7656-4975
Mimoun AzzouzDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385A Glossop Road, Sheffield, S10 2HQ, UK. m.azzouz@sheffield.ac.uk.
University of Sheffield · GB

Funding

European Research Council 294745Medical Research Council G1001492
6 · The paper itself

Abstract

Adeno-associated viruses (AAVs) are attractive gene therapy vectors due to their low toxicity, high stability, and rare integration into the host genome. Expressing ligands on the viral capsid can re-target AAVs to new cell types, but limited sites have been identified on the capsid that tolerate a peptide insertion. Here, we incorporated a site-specific tetracysteine sequence into the AAV serotype 9 (AAV9) capsid, to permit labelling of viral particles with either a fluorescent dye or biotin. We demonstrate that fluorescently labelled particles are detectable in vitro, and explore the utility of the method in vivo in mice with time-lapse imaging. We exploit the biotinylated viral particles to generate two distinct AAV interactomes, and identify several functional classes of proteins that are highly represented: actin/cytoskeletal protein binding, RNA binding, RNA splicing/processing, chromatin modifying, intracellular trafficking and RNA transport proteins. To examine the biological relevance of the capsid interactome, we modulated the expression of two proteins from the interactomes prior to AAV transduction. Blocking integrin αVβ6 receptor function reduced AAV9 transduction, while reducing histone deacetylase 4 (HDAC4) expression enhanced AAV transduction. Our method demonstrates a strategy for inserting motifs into the AAV capsid without compromising viral titer or infectivity.

Indexed as

MutationAmino Acid SequenceAnimalsAntigens, NeoplasmCapsidCell Line, TumorCysteineDependovirusGenetic VectorsHEK293 CellsHistone DeacetylasesHumansIntegrinsMaleimidesMiceOptical ImagingAntigens, NeoplasmCysteineHDAC4 protein, humanHistone Deacetylasesintegrin alphavbeta6IntegrinsMaleimidesRepressor ProteinsViral Proteins

Identifiers

PMID29116194
PMCPMC5676692
OpenAlexW2765807033

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.