Evidence map›Paper›PMID 32286269›Full record

ArticleNature communications2020

Imaging small molecule-induced endosomal escape of siRNA.

Hampus Du Rietz, Hampus Hedlund, Sten Wilhelmson, Pontus Nordenfelt, Anders Wittrup

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
8.1field-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

94 citing papers in PubMed, 181 citations in OpenAlex.

  1. RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026
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  13. RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026
    Review
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  20. Review

34 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

5 authors at 1 institution in 1 country.

Hampus Du RietzDepartment of Clinical Sciences, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-5530-3821
Hampus HedlundDepartment of Clinical Sciences, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-3168-7920
Sten WilhelmsonDepartment of Clinical Sciences, Oncology, Faculty of Medicine, Lund University, Lund, Sweden.
Pontus NordenfeltDepartment of Clinical Sciences, Division of Infection Medicine, Faculty of Medicine, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-9481-9951
Anders WittrupDepartment of Clinical Sciences, Oncology, Faculty of Medicine, Lund University, Lund, Sweden. anders.wittrup@med.lu.se.ORCID http://orcid.org/0000-0003-4918-0500
Lund University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small interfering RNAs (siRNAs) are a new class of promising therapeutic molecules that can be used for sequence-specific downregulation of disease-causing genes. However, endosomal entrapment of siRNA is a key hurdle for most delivery strategies, limiting the therapeutic effect. Here, we use live-cell microscopy and cytosolic galectin-9 as a sensor of membrane damage, to probe fundamental properties of endosomal escape of cholesterol-conjugated siRNA induced by endosome-disrupting compounds. We demonstrate efficient release of ligand-conjugated siRNA from vesicles damaged by small molecules, enhancing target knockdown up to ∼47-fold in tumor cells. Still, mismatch between siRNA-containing and drug-targeted endolysosomal compartments limits siRNA activity improvement. We also show widespread endosomal damage in macroscopic tumor spheroids after small molecule treatment, substantially improving siRNA delivery and knockdown throughout the spheroid. We believe the strategy to characterize endosomal escape presented here will be widely applicable, facilitating efforts to improve delivery of siRNA and other nucleic acid-based therapeutics.

Indexed as

Imaging, Three-DimensionalCell MembraneCell SurvivalCholesterolCytosolDextransEndosomesGalectinsGene Knockdown TechniquesGreen Fluorescent ProteinsHeLa CellsHumansLysosomesMCF-7 CellsRNA, Small InterferingSmall Molecule LibrariesCholesterolDextransenhanced green fluorescent proteinGalectinsGreen Fluorescent ProteinsLGALS9 protein, humanRNA, Small InterferingSmall Molecule Libraries

Identifiers

PMID32286269
PMCPMC7156650
OpenAlexW3015298423

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.