Evidence map›Paper›PMID 30610181›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

HOPS-dependent endosomal fusion required for efficient cytosolic delivery of therapeutic peptides and small proteins.

Angela Steinauer, Jonathan R LaRochelle, Susan L Knox, Rebecca F Wissner, Samuel Berry, Alanna Schepartz

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review
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  11. Design rules for efficient endosomal escape.bioRxiv : the preprint server for biology · 2023
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. De novo mapping of α-helix recognition sites on protein surfaces using unbiased libraries.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Review
  19. How Do Biomolecules Cross the Cell Membrane?Accounts of chemical research · 2022
    Article
  20. 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

6 authors at 1 institution in 1 country.

Angela SteinauerDepartment of Chemistry, Yale University, New Haven, CT 06520-8107.ORCID 0000-0002-1495-9330
Jonathan R LaRochelleDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103.
Susan L KnoxDepartment of Chemistry, Yale University, New Haven, CT 06520-8107.ORCID 0000-0001-5943-7678
Rebecca F WissnerDepartment of Chemistry, Yale University, New Haven, CT 06520-8107.ORCID 0000-0002-8213-455X
Samuel BerryDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114.ORCID 0000-0002-3480-5988
Alanna SchepartzDepartment of Chemistry, Yale University, New Haven, CT 06520-8107; alanna.schepartz@yale.edu.ORCID 0000-0003-2127-3932
Yale University · US

Funding

Foldamers: Novel Ligands for Diverse Protein SurfacesR01GM074756 · NIGMS · YALE UNIVERSITY · PI SCHEPARTZ, ALANNA · 2005 to 2013
$3.2M
Directing the Mediator Complex: Bivalent approaches to Reconstituting or InhibitiR01CA170741 · NCI · YALE UNIVERSITY · PI SCHEPARTZ, ALANNA, TAATJES, DYLAN J · 2012 to 2016
$1.9M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA170741NIGMS NIH HHS R01 GM074756
6 · The paper itself

Abstract

Protein therapeutics represent a significant and growing component of the modern pharmacopeia, but their potential to treat human disease is limited because most proteins fail to traffic across biological membranes. Recently, we discovered a class of cell-permeant miniature proteins (CPMPs) containing a precisely defined, penta-arginine (penta-Arg) motif that traffics readily to the cytosol and nucleus of mammalian cells with efficiencies that rival those of hydrocarbon-stapled peptides active in animals and man. Like many cell-penetrating peptides (CPPs), CPMPs enter the endocytic pathway; the difference is that CPMPs containing a penta-Arg motif are released efficiently from endosomes, while other CPPs are not. Here, we seek to understand how CPMPs traffic from endosomes into the cytosol and what factors contribute to the efficiency of endosomal release. First, using two complementary cell-based assays, we exclude endosomal rupture as the primary means of endosomal escape. Next, using an RNA interference screen, fluorescence correlation spectroscopy, and confocal imaging, we identify

Indexed as

Cell-Penetrating PeptidesAmino Acid MotifsAutophagy-Related ProteinsCarrier ProteinsCell Line, TumorCytosolEndosomesHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsLysosomal-Associated Membrane Protein 1Lysosomal Membrane ProteinsMembrane FusionProtein Transportrab7 GTP-Binding Proteinsrab GTP-Binding ProteinsAutophagy-Related ProteinsCarrier ProteinsCell-Penetrating PeptidesIntracellular Signaling Peptides and ProteinsLAMP1 protein, humanLysosomal-Associated Membrane Protein 1Lysosomal Membrane Proteinsrab7 GTP-Binding Proteinsrab7 GTP-binding proteins, humanrab GTP-Binding ProteinsVesicular Transport ProteinsVPS39 protein, humancell-penetrating peptidesendocytosisenzyme replacement therapypeptidomimeticsprotein therapeutics

Identifiers

PMID30610181
PMCPMC6329960
OpenAlexW2884949921

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.