Evidence map›Paper›PMID 39082815›Full record

ArticleJournal of virology2024

Sub-genomic flaviviral RNA elements increase the stability and abundance of recombinant AAV vector transcripts.

Rita M Meganck, Roza Ogurlu, Jiacheng Liu, Sven Moller-Tank, Victor Tse, Leo O Blondel, Alan Rosales, Aaron C Hall, Heather A Vincent, Nathaniel J Moorman and 2 more

Abstract read
In one paragraph

Article in Journal of virology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

12 authors.

Rita M MeganckDepartment of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Roza OgurluDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Jiacheng LiuGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Sven Moller-TankGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Victor TseGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Leo O BlondelDepartment of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Alan RosalesDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Aaron C HallDepartment of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Heather A VincentDepartment of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Nathaniel J MoormanDepartment of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
William F MarzluffDepartment of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Aravind AsokanDepartment of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.ORCID 0000-0001-5563-4877

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
NHLBI NIH HHS R01 HL089221NIGMS NIH HHS R01 GM127708NINDS NIH HHS R01 NS099371
6 · The paper itself

Abstract

Many viruses have evolved structured RNA elements that can influence transcript abundance and translational efficiency, and help evade host immune factors by hijacking cellular machinery during replication. Here, we evaluated the functional impact of sub-genomic flaviviral RNAs (sfRNAs) known to stall exoribonuclease activity, by incorporating these elements into recombinant adeno-associated viral (AAV) genome cassettes. Specifically, sfRNAs from Dengue, Zika, Japanese Encephalitis, Yellow Fever, Murray Valley Encephalitis, and West Nile viruses increased transcript stability and transgene expression compared to a conventional woodchuck hepatitis virus element (WPRE). Further dissection of engineered transcripts revealed that sfRNA elements (i) require incorporation in IMPORTANCE: Viral RNA elements can hijack host cell machinery to control stability of transcripts and consequently, infection. Studies that help better understand such viral elements can provide insights into antiviral strategies and also potentially leverage these features for therapeutic applications. In this study, by incorporating structured flaviviral RNA elements into recombinant adeno-associated viral (AAV) vector genomes, we show improved AAV transcript stability and transgene expression can be achieved, with implications for gene transfer.

Indexed as

DependovirusGenetic VectorsRNA, Viral3' Untranslated RegionsAnimalsExoribonucleasesFlaviviridaeGenome, ViralHEK293 CellsHumansMiceRNA StabilityTransgenes3' Untranslated RegionsExoribonucleasesRNA, ViralAAV vectorsexpressionflavivirusgene therapymRNA stabilitytranslation

Identifiers

PMID39082815
PMCPMC11334430

What OpenQuestion holds

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LicenceCC BY
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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.