Evidence map›Paper›PMID 31718426›Full record

ArticleNucleic acid therapeutics2020

Endocytosis Controls siRNA Efficiency: Implications for siRNA Delivery Vehicle Design and Cell-Specific Targeting.

Daniel Vocelle, Christina Chan, S Patrick Walton

Open access · bronzeAbstract read
In one paragraph

Article in Nucleic acid therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

23 citing papers in PubMed, 30 citations in OpenAlex.

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  13. Research Status and Prospect of Non-Viral Vectors Based on siRNA: A Review.International journal of molecular sciences · 2023
    Review
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  20. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
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

3 authors at 1 institution in 1 country.

Daniel VocelleDepartment of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
Christina ChanDepartment of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
S Patrick WaltonDepartment of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan.
Michigan State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While small interfering RNAs (siRNAs) are commonly used for laboratory studies, development of siRNA therapeutics has been slower than expected, due, in part, to a still limited understanding of the endocytosis and intracellular trafficking of siRNA-containing complexes. With the recent characterization of multiple clathrin-/caveolin-independent endocytic pathways, that is, those mediated by Graf1, Arf6, and flotillin, it has become clear that the endocytic mechanism influences subsequent intracellular processing of the internalized cargo. To explore siRNA delivery in light of these findings, we developed a novel assay that differentiates uptake by each of the endocytic pathways and can be used to determine whether endocytosis by a pathway leads to the initiation of RNA interference (RNAi). Using Lipofectamine 2000 (LF2K), we determined the endocytosis pathway leading to active silencing (whether by clathrin, caveolin, Arf6, Graf1, flotillin, or macropinocytosis) across multiple cell types (HeLa, H1299, HEK293, and HepG2). We showed that LF2K is internalized by Graf1-, Arf6-, or flotillin-mediated endocytosis for the initiation of RNAi, depending on cell type. In addition, we found that a portion of siRNA-containing complexes is internalized by pathways that do not lead to initiation of silencing. Inhibition of these pathways enhanced intracellular levels of siRNAs with concomitant enhancement of silencing.

Indexed as

Gene Transfer TechniquesADP-Ribosylation Factor 6ADP-Ribosylation FactorsCaveolinsClathrinEndocytosisGene SilencingGTPase-Activating ProteinsHEK293 CellsHeLa CellsHumansMembrane ProteinsRNA InterferenceRNA, Small InterferingRNA TransportSignal TransductionADP-Ribosylation Factor 6ADP-Ribosylation FactorsARF6 protein, humanARHGAP26 protein, humanCaveolinsClathrinflotillinsGTPase-Activating ProteinsMembrane ProteinsRNA, Small Interferingclathrin/caveolin-independent endocytosisLipofectamine 2000siRNA delivery

Identifiers

PMID31718426
PMCPMC6987736
OpenAlexW2983910901

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.