Evidence map›Paper›PMID 31937944›Full record

ArticleNature biomedical engineering2020

Reduction of the therapeutic dose of silencing RNA by packaging it in extracellular vesicles via a pre-microRNA backbone.

Ryan Reshke, James A Taylor, Alexandre Savard, Huishan Guo, Luke H Rhym, Piotr S Kowalski, My Tran Trung, Charles Campbell, Wheaton Little, Daniel G Anderson and 1 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
8.3field-weighted citation impact, top 1% 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

86 citing papers in PubMed, 151 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Endogenous Engineering Reprograms Extracellular Vesicles for Enhanced Therapeutic Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Rethinking Extracellular Vesicle Signaling.Advanced materials (Deerfield Beach, Fla.) · 2026
    Article
  10. Current trends in exosomes as therapeutic drug delivery systems.Naunyn-Schmiedeberg's archives of pharmacology · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Exosome miRNA sorting controlled by RNA-binding protein-motif interactions.Extracellular vesicles and circulating nucleic acids · 2025
    Review
  18. Review
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Ryan Reshke *Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
James A Taylor *Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
Alexandre Savard *Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
Huishan GuoDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
Luke H RhymThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Piotr S KowalskiThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
My Tran TrungDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
Charles CampbellDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
Wheaton LittleCentral Nervous System Disorders Drug Discovery Unit, Takeda Pharmaceuticals, Cambridge, MA, USA.
Daniel G AndersonThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Derrick GibbingsDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada. gibbings@uottawa.ca.ORCID http://orcid.org/0000-0002-9305-8898
University of Ottawa · CAMassachusetts Institute of Technology · USTakeda (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A small percentage of the short interfering RNA (siRNA) delivered via passive lipid nanoparticles and other delivery vehicles reaches the cytoplasm of cells. The high doses of siRNA and delivery vehicle that are thus required to achieve therapeutic outcomes can lead to toxicity. Here, we show that the integration of siRNA sequences into a Dicer-independent RNA stem-loop based on pre-miR-451 microRNA-which is highly enriched in small extracellular vesicles secreted by many cell types-reduces the expression of the genes targeted by the siRNA in the liver, intestine and kidney glomeruli of mice at siRNA doses that are at least tenfold lower than the siRNA doses typically delivered via lipid nanoparticles. Small extracellular vesicles that efficiently package siRNA can significantly reduce its therapeutic dose.

Indexed as

AnimalsCell Line, TumorDrug Delivery SystemsExtracellular VesiclesGene ExpressionHumansMiceMicroRNAsMotor NeuronsNanoparticlesRNA InterferenceRNA, Small InterferingMicroRNAsMIRN451 microRNA, humanRNA, Small Interfering

Identifiers

PMID31937944
OpenAlexW2999705542

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.