Evidence map›Paper›PMID 25072692›Full record

ArticleMolecular therapy. Nucleic acids2014

A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an HDV Ribozyme and a Short Hairpin RNA.

Robert J Scarborough, Michel V Lévesque, Etienne Boudrias-Dalle, Ian C Chute, Sylvanne M Daniels, Rodney J Ouellette, Jean-Pierre Perreault, Anne Gatignol

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2014. 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 22% 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, 20 citations in OpenAlex.

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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

8 authors at 3 institutions in 1 country.

Robert J Scarborough1] Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Montréal, Québec, Canada [2] Department of Microbiology & Immunology, McGill University, Montréal, Québec, Canada.
Michel V LévesqueDépartement de Biochimie, RNA Group/Groupe ARN, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Etienne Boudrias-Dalle1] Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Montréal, Québec, Canada [2] Department of Microbiology & Immunology, McGill University, Montréal, Québec, Canada.
Ian C ChuteAtlantic Cancer Research Institute, Moncton, New Brunswick, Canada.
Sylvanne M Daniels1] Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Montréal, Québec, Canada [2] Department of Microbiology & Immunology, McGill University, Montréal, Québec, Canada.
Rodney J OuelletteAtlantic Cancer Research Institute, Moncton, New Brunswick, Canada.
Jean-Pierre PerreaultDépartement de Biochimie, RNA Group/Groupe ARN, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Anne Gatignol1] Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Montréal, Québec, Canada [2] Department of Microbiology & Immunology, McGill University, Montréal, Québec, Canada [3] Department of Medicine, McGill University, Montréal, Québec, Canada.
McGill University · CAAtlantic Cancer Research Institute · CAUniversité de Sherbrooke · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antisense-based molecules targeting HIV-1 RNA have the potential to be used as part of gene or drug therapy to treat HIV-1 infection. In this study, HIV-1 RNA was screened to identify more conserved and accessible target sites for ribozymes based on the hepatitis delta virus motif. Using a quantitative screen for effects on HIV-1 production, we identified a ribozyme targeting a highly conserved site in the Gag coding sequence with improved inhibitory potential compared to our previously described candidates targeting the overlapping Tat/Rev coding sequence. We also demonstrate that this target site is highly accessible to short hairpin directed RNA interference, suggesting that it may be available for the binding of antisense RNAs with different modes of action. We provide evidence that this target site is structurally conserved in diverse viral strains and that it is sufficiently different from the human transcriptome to limit off-target effects from antisense therapies. We also show that the modified hepatitis delta virus ribozyme is more sensitive to a mismatch in its target site compared to the short hairpin RNA. Overall, our results validate the potential of a new target site in HIV-1 RNA to be used for the development of antisense therapies.

Identifiers

PMID25072692
PMCPMC4121520
OpenAlexW2108528276

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.