Evidence map›Paper›PMID 25539920›Full record

ArticleNucleic acids research2015

Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors.

Soroush T Sarvestani, H James Stunden, Mark A Behlke, Samuel C Forster, Claire E McCoy, Michelle D Tate, Jonathan Ferrand, Kim A Lennox, Eicke Latz, Bryan R G Williams and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

26 citing papers in PubMed, 45 citations in OpenAlex.

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  15. MicroRNA Targets for Asthma Therapy.Advances in experimental medicine and biology · 2021
    Article
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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

11 authors at 5 institutions in 4 countries.

Soroush T SarvestaniCentre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Victoria 3168, Australia Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia.
H James StundenInstitute of Innate Immunity, Biomedical Center, University Hospitals Bonn, Bonn 53127, Germany.
Mark A BehlkeIntegrated DNA Technologies Inc., Coralville, IA 52241, USA.
Samuel C ForsterHost-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Claire E McCoyCentre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Victoria 3168, Australia Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia.
Michelle D TateDepartment of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria 3168, Australia.
Jonathan FerrandCentre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Victoria 3168, Australia Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia.
Kim A LennoxIntegrated DNA Technologies Inc., Coralville, IA 52241, USA.
Eicke LatzInstitute of Innate Immunity, Biomedical Center, University Hospitals Bonn, Bonn 53127, Germany Division of Infectious Diseases & Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA Deutsches Zentrum für Neurodegenerative Erkrankungen, Bonn 53127, Germany.
Bryan R G WilliamsCentre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Victoria 3168, Australia Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia michael.gantier@mimr-phi.org.
Michael P GantierCentre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Victoria 3168, Australia Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia michael.gantier@mimr-phi.org.
Hudson Institute of Medical Research · AUIntegrated DNA Technologies (United States) · USUniversity Hospital Bonn · DEMonash University · AUWellcome Sanger Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anti-microRNA (miRNA) oligonucleotides (AMOs) with 2'-O-Methyl (2'OMe) residues are commonly used to study miRNA function and can achieve high potency, with low cytotoxicity. Not withstanding this, we demonstrate the sequence-dependent capacity of 2'OMe AMOs to inhibit Toll-like receptor (TLR) 7 and 8 sensing of immunostimulatory RNA, independent of their miRNA-targeting function. Through a screen of 29 AMOs targeting common miRNAs, we found a subset of sequences highly inhibitory to TLR7 sensing in mouse macrophages. Interspecies conservation of this inhibitory activity was confirmed on TLR7/8 activity in human peripheral blood mononuclear cells. Significantly, we identified a core motif governing the inhibitory activity of these AMOs, which is present in more than 50 AMOs targeted to human miRNAs in miRBaseV20. DNA/locked nucleic acids (LNA) AMOs synthesized with a phosphorothioate backbone also inhibited TLR7 sensing in a sequence-dependent manner, demonstrating that the off-target effects of AMOs are not restricted to 2'OMe modification. Taken together, our work establishes the potential for off-target effects of AMOs on TLR7/8 function, which should be taken into account in their therapeutic development and in vivo application.

Indexed as

Adjuvants, ImmunologicAnimalsBase SequenceHEK293 CellsHumansMiceMicroRNAsNucleotide MotifsOligonucleotidesRNAToll-Like Receptor 7Toll-Like Receptor 8Adjuvants, ImmunologicMicroRNAsOligonucleotidesRNATLR7 protein, humanTLR8 protein, humanToll-Like Receptor 7Toll-Like Receptor 8

Identifiers

PMID25539920
PMCPMC4333393
OpenAlexW2100037149

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.