Evidence map›Paper›PMID 29437530›Full record

ArticleNucleic acid therapeutics2018

Endosomal Escape of Antisense Oligonucleotides Internalized by Stabilin Receptors Is Regulated by Rab5C and EEA1 During Endosomal Maturation.

Colton M Miller, W Brad Wan, Punit P Seth, Edward N Harris

Open access · bronzeAbstract read
In one paragraph

Article in Nucleic acid therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 47 citations in OpenAlex.

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  20. RNA-PROTACs: Degraders of RNA-Binding Proteins.Angewandte Chemie (International ed. in English) · 2021
    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

4 authors at 2 institutions in 1 country.

Colton M Miller1 Department of Biochemistry, University of Nebraska , Lincoln, Nebraska.
W Brad Wan2 Ionis Pharmaceuticals , Carlsbad, California.
Punit P Seth2 Ionis Pharmaceuticals , Carlsbad, California.
Edward N Harris1 Department of Biochemistry, University of Nebraska , Lincoln, Nebraska.
Ionis Pharmaceuticals (United States) · USUniversity of Nebraska–Lincoln · US

Funding

Liver-Mediated Clearance of Low Molecular Weight HeparinsR01HL130864 · NHLBI · UNIVERSITY OF NEBRASKA LINCOLN · PI HARRIS, EDWARD N · 2016 to 2019
$1.6M
NHLBI NIH HHS R01 HL130864
6 · The paper itself

Abstract

Second-generation (Gen 2) Antisense oligonucleotides (ASOs) show increased nuclease stability and affinity for their RNA targets, which has translated to improved potency and therapeutic index in the clinic. Gen 2 ASOs are typically modified using the phosphorothioate (PS) backbone modification, which enhances ASO interactions with plasma, cell surface, and intracellular proteins. This facilitates ASO distribution to peripheral tissues and also promotes cellular uptake after injection into animals. Previous work identified that Stabilin receptors specifically internalize PS-ASOs in the sinusoidal endothelial cells of the liver and the spleen. By modulating expression of specific proteins involved in the trafficking and maturation of the endolysosomal compartments, we show that Rab5C and EEA1 in the early endosomal pathway, and Rab7A and lysobisphosphatidic acid in the late endosomal pathway, are important for trafficking of PS-ASOs and facilitate their escape from endolysosomal compartments after Stabilin-mediated internalization. In conclusion, this work identifies key rate-limiting proteins in the pathway for PS-ASO translocation and escape from the endosome.

Indexed as

Cell Adhesion Molecules, NeuronalDocosahexaenoic AcidsEndocytosisEndosomesHEK293 CellsHumansOligonucleotides, AntisensePhosphorothioate Oligonucleotidesrab5 GTP-Binding Proteinsrab7 GTP-Binding Proteinsrab GTP-Binding ProteinsReceptors, Lymphocyte HomingRNA, Long NoncodingVesicular Transport ProteinsCell Adhesion Molecules, NeuronalDocosahexaenoic Acidsearly endosome antigen 1MALAT1 long non-coding RNA, humanOligonucleotides, AntisensePhosphorothioate OligonucleotidesRAB5C protein, humanrab5 GTP-Binding Proteinsrab7 GTP-Binding Proteinsrab GTP-Binding ProteinsReceptors, Lymphocyte HomingRNA, Long NoncodingSTAB1 protein, humanVesicular Transport Proteinsantisense oligonucleotideASOendosome escapeendosome maturationStabilin

Identifiers

PMID29437530
PMCPMC5899299
OpenAlexW2788751517

What OpenQuestion holds

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Registered trials

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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.