Evidence map›Paper›PMID 26789413›Full record

ArticleNucleic acid therapeutics2016

2'Fluoro Modification Differentially Modulates the Ability of RNAs to Activate Pattern Recognition Receptors.

Youngju Lee, Johannes H Urban, Li Xu, Bruce A Sullenger, Jaewoo Lee

Open access · greenAbstract read
In one paragraph

Article in Nucleic acid therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 58 citations in OpenAlex.

  1. Review
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  9. Review
  10. Assessment of Intracellular Compartmentalization of RNA Nanostructures.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  11. Discriminating Immunorecognition Pathways Activated by RNA Nanostructures.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  12. Therapeutic Potential of Aptamer-Protein Interactions.ACS pharmacology & translational science · 2022
    Review
  13. Review
  14. Article
  15. 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

5 authors at 1 institution in 1 country.

Youngju Lee1 Division of Surgical Sciences, Department of Surgery, Duke University , Durham, North Carolina.
Johannes H Urban1 Division of Surgical Sciences, Department of Surgery, Duke University , Durham, North Carolina.
Li Xu1 Division of Surgical Sciences, Department of Surgery, Duke University , Durham, North Carolina.
Bruce A Sullenger1 Division of Surgical Sciences, Department of Surgery, Duke University , Durham, North Carolina.
Jaewoo Lee1 Division of Surgical Sciences, Department of Surgery, Duke University , Durham, North Carolina.
Duke University · US

Funding

Translational Research Skills Development Core (TRSDC): Training Future GeneratiU54HL112307 · NHLBI · DUKE UNIVERSITY · PI BECKER, RICHARD CLINTON, SULLENGER, BRUCE ALAN · 2012 to 2016
$11.1M
RNA aptamers as cell surface receptor agonists and siRNA delivery agentsR01CA129190 · NCI · DUKE UNIVERSITY · PI SULLENGER, BRUCE ALAN · 2009 to 2012
$1.0M
NCI NIH HHS R01 CA129190NHLBI NIH HHS U54 HL112307
6 · The paper itself

Abstract

Although the use of RNAs has enormous therapeutic potential, these RNA-based therapies can trigger unwanted inflammatory responses by the activation of pattern recognition receptors (PRRs) and cause harmful side effects. In contrast, the immune activation by therapeutic RNAs can be advantageous for treating cancers. Thus, the immunogenicity of therapeutic RNAs should be deliberately controlled depending on the therapeutic applications of RNAs. In this study, we demonstrated that RNAs containing 2'fluoro (2'F) pyrimidines differentially controlled the activation of PRRs. The activity of RNAs that stimulate toll-like receptors 3 and 7 was abrogated by the incorporation of 2'F pyrimidine. By contrast, incorporation of 2'F pyrimidines enhanced the activity of retinoic acid-inducible gene 1-stimulating RNAs. Furthermore, we found that transfection with RNAs containing 2'F pyrimidine and 5' triphosphate (5'ppp) increased cell death and interferon-β expression in human cancer cells compared with transfection with 2'hydroxyl 5'ppp RNAs, whereas RNAs containing 2'O-methyl pyrimidine and 5'ppp completely abolished the induction of cell death and cytokine expression in the cells. Our findings suggest that incorporation of 2'F and 2'O-methyl nucleosides is a facile approach to differentially control the ability of therapeutic RNAs to activate or limit immune and inflammatory responses depending on therapeutic applications.

Indexed as

Cell DeathCytokinesFloxuridineGene Expression RegulationHumansNucleic Acid ConformationReceptors, Pattern RecognitionRNAToll-Like Receptor 32'fluoro-2'-deoxyuridineCytokinesFloxuridineReceptors, Pattern RecognitionRNATLR3 protein, humanToll-Like Receptor 3

Identifiers

PMID26789413
PMCPMC4900224
OpenAlexW2281744815

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.