Evidence map›Paper›PMID 22294662›Full record

ArticleRNA (New York, N.Y.)2012

Comprehensive evaluation of canonical versus Dicer-substrate siRNA in vitro and in vivo.

Donald J Foster, Scott Barros, Rick Duncan, Sarfraz Shaikh, William Cantley, Amy Dell, Elena Bulgakova, Jonathan O'Shea, Nate Taneja, Satya Kuchimanchi and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Hepatic RNA Interference: Delivery by Synthetic Vectors.Drug delivery and translational research · 2014
    Article
  17. Article
  18. Knockdown of β-catenin with dicer-substrate siRNAs reduces liver tumor burden in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2014
    Article
  19. Article
  20. Article
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 2 institutions in 1 country.

Donald J FosterAlnylam Pharmaceuticals, Cambridge, Massachusetts 02142, USA. dfoster@alnylam.com
Scott Barros
Rick Duncan
Sarfraz Shaikh
William Cantley
Amy Dell
Elena Bulgakova
Jonathan O'Shea
Nate Taneja
Satya Kuchimanchi
Christopher B Sherrill
Akin Akinc
Gregory Hinkle
Amy C Seila White
Bo Pang
Klaus Charisse
Rachel Meyers
Muthiah Manoharan
Sayda M Elbashir
Alnylam Pharmaceuticals (United States) · USModerna Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Since the discovery of RNA interference (RNAi), researchers have identified a variety of small interfering RNA (siRNA) structures that demonstrate the ability to silence gene expression through the classical RISC-mediated mechanism. One such structure, termed "Dicer-substrate siRNA" (dsiRNA), was proposed to have enhanced potency via RISC-mediated gene silencing, although a comprehensive comparison of canonical siRNAs and dsiRNAs remains to be described. The present study evaluates the in vitro and in vivo activities of siRNAs and dsiRNAs targeting Phosphatase and Tensin Homolog (PTEN) and Factor VII (FVII). More than 250 compounds representing both siRNA and dsiRNA structures were evaluated for silencing efficacy. Lead compounds were assessed for duration of silencing and other key parameters such as cytokine induction. We identified highly active compounds from both canonical siRNAs and 25/27 dsiRNAs. Lead compounds were comparable in potency both in vitro and in vivo as well as duration of silencing in vivo. Duplexes from both structural classes tolerated 2'-OMe chemical modifications well with respect to target silencing, although some modified dsiRNAs demonstrated reduced activity. On the other hand, dsiRNAs were more immunostimulatory as compared with the shorter siRNAs, both in vitro and in vivo. Because the dsiRNA structure does not confer any appreciable benefits in vitro or in vivo while demonstrating specific liabilities, further studies are required to support their applications in RNAi therapeutics.

Indexed as

RNA InterferenceAnimalsBase SequenceFactor VIIFemaleHeLa CellsHumansMiceMice, Inbred C57BLPTEN PhosphohydrolaseRatsRibonuclease IIIRNA-Induced Silencing ComplexRNA, Small InterferingFactor VIIPTEN PhosphohydrolaseRibonuclease IIIRNA-Induced Silencing ComplexRNA, Small Interfering

Identifiers

PMID22294662
PMCPMC3285942
OpenAlexW2106606228

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.