Evidence map›Paper›PMID 19144911›Full record

ArticleRNA (New York, N.Y.)2009

MicroRNA-like off-target transcript regulation by siRNAs is species specific.

Julja Burchard, Aimee L Jackson, Vladislav Malkov, Rachel H V Needham, Yejun Tan, Steven R Bartz, Hongyue Dai, Alan B Sachs, Peter S Linsley

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in RNA (New York, N.Y.), 2009. 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
4.8field-weighted citation impact, top 4% 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, 78 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

9 authors at 1 institution in 1 country.

Julja BurchardRosetta Inpharmatics LLC, Seattle, Washington 98109, USA.
Aimee L Jackson
Vladislav Malkov
Rachel H V Needham
Yejun Tan
Steven R Bartz
Hongyue Dai
Alan B Sachs
Peter S Linsley
Rosetta Stone (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

siRNAs mediate sequence-specific gene silencing in cultured mammalian cells but also silence unintended transcripts. Many siRNA off-target transcripts match the guide-strand "seed region," similar to the way microRNAs match their target sites. The extent to which this seed-matched, microRNA-like, off-target silencing affects the specificity of therapeutic siRNAs in vivo is currently unknown. Here, we compare microRNA-like off-target regulations in mouse liver in vivo with those seen in cell culture for a series of therapeutic candidate siRNAs targeting Apolipoprotein B (APOB). Each siRNA triggered regulation of consistent microRNA-like off-target transcripts in mouse livers and in cultured mouse liver tumor cells. In contrast, there was only random overlap between microRNA-like off-target transcripts from cultured human and mouse liver tumor cells. Therefore, siRNA therapeutics may trigger microRNA-like silencing of many unintended targets in vivo, and the potential toxicities caused by these off-target gene regulations cannot be accurately assessed in rodent models.

Indexed as

Gene Silencing3' Untranslated RegionsAnimalsApolipoproteins BCell Line, TumorCells, CulturedGene Expression ProfilingHumansMiceMicroRNAsRNA, Small InterferingSelection, GeneticSpecies SpecificityTranscription, Genetic3' Untranslated RegionsApolipoproteins BMicroRNAsRNA, Small Interfering

Identifiers

PMID19144911
PMCPMC2648714
OpenAlexW2148496991

What OpenQuestion holds

Textmetadata
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.