Evidence map›Paper›PMID 19506055›Full record

ArticleAntimicrobial agents and chemotherapy2009

RNA interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent antiviral strategy.

Rene Alvarez, Sayda Elbashir, Todd Borland, Ivanka Toudjarska, Philipp Hadwiger, Mathias John, Ingo Roehl, Svetlana Shulga Morskaya, Rick Martinello, Jeffrey Kahn and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 2% 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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.

  1. Viral infection in community-acquired pneumonia: a systematic review and meta-analysis.European respiratory review : an official journal of the European Respiratory Society · 2016
    Pooled it
  2. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus.Proceedings of the National Academy of Sciences of the United States of America · 2010
    Trial
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  14. Can pulmonary RNA delivery improve our pandemic preparedness?Journal of controlled release : official journal of the Controlled Release Society · 2022
    Article
  15. Article
  16. Review
  17. Therapeutic siRNA: state of the art.Signal transduction and targeted therapy · 2020
    Review
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  20. Review

6 more citing papers are in PubMed but not listed here.

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

19 authors at 5 institutions in 2 countries.

Rene AlvarezAlnylam Pharmaceuticals, 300 Third Street, Cambridge, MA 02142, USA.
Sayda Elbashir
Todd Borland
Ivanka Toudjarska
Philipp Hadwiger
Mathias John
Ingo Roehl
Svetlana Shulga Morskaya
Rick Martinello
Jeffrey Kahn
Mark Van Ranst
Ralph A Tripp
John P DeVincenzo
Rajendra Pandey
Martin Maier
Lubomir Nechev
Muthiah Manoharan
Victor Kotelianski
Rachel Meyers
Alnylam Pharmaceuticals (United States) · USYale University · USKU Leuven · BEUniversity of Georgia · USUniversity of Tennessee Health Science Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We describe the design and characterization of a potent human respiratory syncytial virus (RSV) nucleocapsid gene-specific small interfering RNA (siRNA), ALN-RSV01. In in vitro RSV plaque assays, ALN-RSV01 showed a 50% inhibitory concentration of 0.7 nM. Sequence analysis of primary isolates of RSV showed that the siRNA target site was absolutely conserved in 89/95 isolates, and ALN-RSV01 demonstrated activity against all isolates, including those with single-mismatch mutations. In vivo, intranasal dosing of ALN-RSV01 in a BALB/c mouse model resulted in potent antiviral efficacy, with 2.5- to 3.0-log-unit reductions in RSV lung concentrations being achieved when ALN-RSV01 was administered prophylactically or therapeutically in both single-dose and multidose regimens. The specificity of ALN-RSV01 was demonstrated in vivo by using mismatch controls; and the absence of an immune stimulatory mechanism was demonstrated by showing that nonspecific siRNAs that induce alpha interferon and tumor necrosis factor alpha lack antiviral efficacy, while a chemically modified form of ALN-RSV01 lacking measurable immunostimulatory capacity retained full activity in vivo. Furthermore, an RNA interference mechanism of action was demonstrated by the capture of the site-specific cleavage product of the RSV mRNA via rapid amplification of cDNA ends both in vitro and in vivo. These studies lay a solid foundation for the further investigation of ALN-RSV01 as a novel therapeutic antiviral agent for clinical use by humans.

Indexed as

AnimalsAntiviral AgentsChlorocebus aethiopsCricetinaeFemaleGenotypeHumansInterferon-alphaLeukocytes, MononuclearMiceNucleocapsidPhylogenyRespiratory Syncytial Virus, HumanRespiratory Syncytial Virus InfectionsRNA InterferenceRNA, Small InterferingAntiviral AgentsInterferon-alphaRNA, Small InterferingTumor Necrosis Factor-alpha

Identifiers

PMID19506055
PMCPMC2737834
OpenAlexW2131179865

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.