Evidence map›Paper›PMID 19729514›Full record

ArticleNucleic acids research2009

Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation.

Rachael Kenworthy, Diana Lambert, Feng Yang, Nan Wang, Zihong Chen, Haizhen Zhu, Fanxiu Zhu, Chen Liu, Kui Li, Hengli Tang

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Review
  3. Molecular therapy. Nucleic acids · 2022
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  17. Atelocollagen-mediated systemic delivery prevents immunostimulatory adverse effects of siRNA in mammals.Molecular therapy : the journal of the American Society of Gene Therapy · 2012
    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

10 authors at 4 institutions in 1 country.

Rachael KenworthyDepartment of Biological Science, Florida State University, Tallahassee, FL 32306-4295, USA.
Diana Lambert
Feng Yang
Nan Wang
Zihong Chen
Haizhen Zhu
Fanxiu Zhu
Chen Liu
Kui Li
Hengli Tang
University of Tennessee Health Science Center · USFlorida State University · USThe University of Texas Medical Branch at Galveston · USUniversity of Florida · US

Funding

Role of TLR3 Signaling in Control of HCVR01AI069285 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI LI, KUI · 2007 to 2016
$2.5M
Role of KSHV ORF45 in Viral Immune Evasion &ReplicationR01DE016680 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI ZHU, FANXIU · 2005 to 2015
$2.5M
Role of TLR3 Signaling in Control of HCVR56AI069285 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI LI, KUI · 2012 to 2012
$300k
NIAID NIH HHS AI069285NIAID NIH HHS R01 AI069285NIAID NIH HHS R56 AI069285NIDCR NIH HHS DE016680NIDCR NIH HHS R01 DE016680
6 · The paper itself

Abstract

Activation of the type I interferon (IFN) pathway by small interfering RNA (siRNA) is a major contributor to the off-target effects of RNA interference in mammalian cells. While IFN induction complicates gene function studies, immunostimulation by siRNAs may be beneficial in certain therapeutic settings. Various forms of siRNA, meeting different compositional and structural requirements, have been reported to trigger IFN activation. The consensus is that intracellularly expressed short-hairpin RNAs (shRNAs) are less prone to IFN activation because they are not detected by the cell-surface receptors. In particular, lentiviral vector-mediated transduction of shRNAs has been reported to avoid IFN response. Here we identify a shRNA that potently activates the IFN pathway in human cells in a sequence- and 5'-triphosphate-dependent manner. In addition to suppressing its intended mRNA target, expression of the shRNA results in dimerization of interferon regulatory factor-3, activation of IFN promoters and secretion of biologically active IFNs into the extracellular medium. Delivery by lentiviral vector transduction did not avoid IFN activation by this and another, unrelated shRNA. We also demonstrated that retinoic-acid-inducible gene I, and not melanoma differentiation associated gene 5 or toll-like receptor 3, is the cytoplasmic sensor for intracellularly expressed shRNAs that trigger IFN activation.

Indexed as

Cell LineCyclophilinsDEAD Box Protein 58DEAD-box RNA HelicasesGenetic VectorsHumansInterferonsLentivirusPromoter Regions, GeneticReceptors, ImmunologicRNA, UntranslatedTransduction, GeneticCyclophilinsDEAD Box Protein 58DEAD-box RNA HelicasesInterferonsReceptors, ImmunologicRIGI protein, humanRNA, Untranslated

Identifiers

PMID19729514
PMCPMC2770676
OpenAlexW1987505466

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.