Evidence map›Paper›PMID 22253019›Full record

ArticleNucleic acids research2012

mRNA knockdown by single strand RNA is improved by chemical modifications.

Henry J Haringsma, Jenny J Li, Ferdie Soriano, Denise M Kenski, W Michael Flanagan, Aarron T Willingham

Abstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Article
  2. Advances in modification and delivery of nucleic acid drugs.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Development of Novel Small Hairpin RNAs That do not Require Processing by Dicer or AGO2.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Base modification strategies to modulate immune stimulation by an siRNA.Chembiochem : a European journal of chemical biology · 2015
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Design of siRNA Therapeutics from the Molecular Scale.Pharmaceuticals (Basel, Switzerland) · 2013
    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

6 authors.

Henry J HaringsmaSirna Therapeutics, 1700 Owens Street, Fourth Floor, San Francisco, CA 94158, USA.
Jenny J Li
Ferdie Soriano
Denise M Kenski
W Michael Flanagan
Aarron T Willingham

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While RNAi has traditionally relied on RNA duplexes, early evaluation of siRNAs demonstrated activity of the guide strand in the absence of the passenger strand. However, these single strands lacked the activity of duplex RNAs. Here, we report the systematic use of chemical modifications to optimize single-strand RNA (ssRNA)-mediated mRNA knockdown. We identify that 2'F ribose modifications coupled with 5'-end phosphorylation vastly improves ssRNA activity both in vitro and in vivo. The impact of specific chemical modifications on ssRNA activity implies an Ago-mediated mechanism but the hallmark mRNA cleavage sites were not observed which suggests ssRNA may operate through a mechanism beyond conventional Ago2 slicer activity. While currently less potent than duplex siRNAs, with additional chemical optimization and alternative routes of delivery, chemically modified ssRNAs could represent a powerful RNAi platform.

Indexed as

RNA InterferenceAnimalsArgonaute ProteinsCell LineMiceMice, Inbred C57BLPhosphorylationRNA, MessengerRNA, Small InterferingRNA, Small UntranslatedArgonaute ProteinsRNA, MessengerRNA, Small InterferingRNA, Small Untranslated

Identifiers

PMID22253019
PMCPMC3351186

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.