Evidence map›Paper›PMID 22287630›Full record

ArticleNucleic acids research2012

In vivo screening of modified siRNAs for non-specific antiviral effect in a small fish model: number and localization in the strands are important.

Brian Dall Schyth, Jesper Bertram Bramsen, Malgorzata Maria Pakula, Sekar Larashati, Jørgen Kjems, Jesper Wengel, Niels Lorenzen

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Gene therapy and kidney diseases.Molecular therapy. Methods & clinical development · 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

7 authors at 4 institutions in 2 countries.

Brian Dall SchythDepartment of Poultry, Fish and Fur Animals, National Veterinary Institute, Technical University of Denmark, Hangøvej 2, DK-8200 Aarhus N. bdsc@vet.dtu.dk
Jesper Bertram Bramsen
Malgorzata Maria Pakula
Sekar Larashati
Jørgen Kjems
Jesper Wengel
Niels Lorenzen
Technical University of Denmark · DKNational Institute of Animal Science · KRAarhus University · DKUniversity of Southern Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small interfering RNAs (siRNAs) are promising new active compounds in gene medicine but the induction of non-specific immune responses following their delivery continues to be a serious problem. With the purpose of avoiding such effects chemically modified siRNAs are tested in screening assay but often only examining the expression of specific immunologically relevant genes in selected cell populations typically blood cells from treated animals or humans. Assays using a relevant physiological state in biological models as read-out are not common. Here we use a fish model where the innate antiviral effect of siRNAs is functionally monitored as reduced mortality in challenge studies involving an interferon sensitive virus. Modifications with locked nucleic acid (LNA), altritol nucleic acid (ANA) and hexitol nucleic acid (HNA) reduced the antiviral protection in this model indicative of altered immunogenicity. For LNA modified siRNAs, the number and localization of modifications in the single strands was found to be important and a correlation between antiviral protection and the thermal stability of siRNAs was found. The previously published sisiRNA will in some sequences, but not all, increase the antiviral effect of siRNAs. The applied fish model represents a potent tool for conducting fast but statistically and scientifically relevant evaluations of chemically optimized siRNAs with respect to non-specific antiviral effects in vivo.

Indexed as

AnimalsAntiviral AgentsDrug Evaluation, PreclinicalHumansModels, AnimalNucleotide MotifsOligonucleotidesOncorhynchus mykissRNA InterferenceRNA, Small InterferingTemperatureAntiviral Agentslocked nucleic acidOligonucleotidesRNA, Small Interfering

Identifiers

PMID22287630
PMCPMC3378874
OpenAlexW2138058303

What OpenQuestion holds

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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.