Evidence map›Paper›PMID 21750714›Full record

ArticlePloS one2011

siRNA off-target effects can be reduced at concentrations that match their individual potency.

Daniel R Caffrey, Juan Zhao, Zhili Song, Michael E Schaffer, Steven A Haney, Romesh R Subramanian, Albert B Seymour, Jason D Hughes

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. 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
3.5field-weighted citation impact, top 7% 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, 88 citations in OpenAlex.

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  13. Long non-coding RNAs: From disease code to drug role.Acta pharmaceutica Sinica. B · 2021
    Review
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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.

Daniel R CaffreyPfizer Inc, Cambridge, Massachusetts, United States of America. Daniel.Caffrey@umassmed.edu
Juan Zhao
Zhili Song
Michael E Schaffer
Steven A Haney
Romesh R Subramanian
Albert B Seymour
Jason D Hughes
Pfizer (United States) · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USTakeda (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small interfering RNAs (siRNAs) are routinely used to reduce mRNA levels for a specific gene with the goal of studying its function. Several studies have demonstrated that siRNAs are not always specific and can have many off-target effects. The 3' UTRs of off-target mRNAs are often enriched in sequences that are complementary to the seed-region of the siRNA. We demonstrate that siRNA off-targets can be significantly reduced when cells are treated with a dose of siRNA that is relatively low (e.g. 1 nM), but sufficient to effectively silence the intended target. The reduction in off-targets was demonstrated for both modified and unmodified siRNAs that targeted either STAT3 or hexokinase II. Low concentrations reduced silencing of transcripts with complementarity to the seed region of the siRNA. Similarly, off-targets that were not complementary to the siRNA were reduced at lower doses, including up-regulated genes that are involved in immune response. Importantly, the unintended induction of caspase activity following treatment with a siRNA that targeted hexokinase II was also shown to be a concentration-dependent off-target effect. We conclude that off-targets and their related phenotypic effects can be reduced for certain siRNA that potently silence their intended target at low concentrations.

Indexed as

RNA Interference3' Untranslated RegionsBase SequenceCaspase 3Caspase 7Cell Line, TumorCell ProliferationGene Expression ProfilingHexokinaseHumansOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSTAT3 Transcription Factor3' Untranslated RegionsCaspase 3Caspase 7HexokinaseRNA, MessengerRNA, Small InterferingSTAT3 Transcription Factor

Identifiers

PMID21750714
PMCPMC3130022
OpenAlexW1994164143

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.