Evidence map›Paper›PMID 34878926›Full record

ArticleJournal of virology2022

Epigenetic Silencing of Recombinant Adeno-associated Virus Genomes by NP220 and the HUSH Complex.

Anshuman Das, Madhuvanthi Vijayan, Eric M Walton, V Grace Stafford, David N Fiflis, Aravind Asokan

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

49 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Epigenetic regulation of transgenes.Journal of biotechnology · 2026
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  17. Nonclinical strategies and considerations to enable the redosing of gene therapies.Molecular therapy. Methods & clinical development · 2025
    Review
  18. Article
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  20. Article
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

6 authors at 1 institution in 1 country.

Anshuman Das *Department of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.
Madhuvanthi Vijayan *Department of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.
Eric M WaltonDepartment of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.
V Grace StaffordDepartment of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.
David N FiflisDepartment of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.
Aravind AsokanDepartment of Surgery, Duke University School of Medicinegrid.471396.e, Durham, North Carolina, USA.ORCID 0000-0001-5563-4877
Duke University · US

Funding

Determinants of AAV TropismR01HL089221 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Aravind Asokan · 2009 to 2026
$8.1M
RE-ENGINEERING AAV GENOME PACKAGINGR01GM127708 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2018 to 2021
$2.0M
CircRNAs and CNS Gene TransferR01NS099371 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2017 to 2021
$1.9M
HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL089221HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM127708HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS099371NHLBI NIH HHS R01 HL089221NIGMS NIH HHS R01 GM127708NINDS NIH HHS R01 NS099371
6 · The paper itself

Abstract

The single-stranded DNA genome of adeno-associated viruses (AAV) undergoes second-strand synthesis and transcription in the host cell nucleus. While wild-type AAV genomes are naturally silenced upon integration into the host genome, recombinant AAV (rAAV) genomes typically provide robust expression of transgenes persisting as extrachromosomal DNA or episomes. Episomal DNA associating with host histones is subject to epigenetic modifications, although the mechanisms underlying such are not well understood. Here, we provide evidence that the double-stranded DNA binding protein NP220, in association with the human silencing hub (HUSH) complex, mediates transcriptional silencing of single-stranded as well as self-complementary rAAV genomes. In cells lacking NP220 or other components of the HUSH complex, AAV genome transcript levels are increased and correlate with a marked reduction in repressive H3K9 histone methylation marks. We also provide evidence that the AAV capsid (serotype) can profoundly influence NP220-mediated silencing of packaged genomes, indicating potential role(s) for capsid-genome or capsid-host factor interactions in regulating epigenetic silencing of rAAV genomes.

Indexed as

Gene SilencingAntigens, NeoplasmCapsidDependovirusDNA-Binding ProteinsEpigenesis, GeneticGenome, ViralHEK293 CellsHumansMultiprotein ComplexesNuclear ProteinsPhosphoproteinsRNA-Binding ProteinsSerogroupTranscription FactorsTranscription, GeneticAntigens, NeoplasmDNA-Binding ProteinsMPHOSPH8 protein, humanMultiprotein ComplexesNuclear ProteinsPhosphoproteinsPPHLN1 protein, humanRNA-Binding ProteinsTASOR protein, humanTranscription FactorsZNF638 protein, humanAAVDNA damagegene silencinggene therapyvirus-host interactions

Identifiers

PMID34878926
PMCPMC8865469
OpenAlexW4200019166

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.