Evidence map›Paper›PMID 34140497›Full record

ArticleNature communications2021

Unravelling cytosolic delivery of cell penetrating peptides with a quantitative endosomal escape assay.

Serena L Y Teo, Joshua J Rennick, Daniel Yuen, Hareth Al-Wassiti, Angus P R Johnston, Colin W Pouton

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. 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
9.0field-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

94 citing papers in PubMed, 157 citations in OpenAlex.

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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

6 authors at 3 institutions in 2 countries.

Serena L Y Teo *Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Joshua J Rennick *Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-5737-671X
Daniel YuenMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0002-1886-0039
Hareth Al-WassitiMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Angus P R JohnstonMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia. angus.johnston@monash.edu.ORCID http://orcid.org/0000-0001-5611-4515
Colin W PoutonMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia. colin.pouton@monash.edu.ORCID http://orcid.org/0000-0003-0224-3308
Convergent Science (United States) · USMonash University · AUMonash Health · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytosolic transport is an essential requirement but a major obstacle to efficient delivery of therapeutic peptides, proteins and nucleic acids. Current understanding of cytosolic delivery mechanisms remains limited due to a significant number of conflicting reports, which are compounded by low sensitivity and indirect assays. To resolve this, we develop a highly sensitive Split Luciferase Endosomal Escape Quantification (SLEEQ) assay to probe mechanisms of cytosolic delivery. We apply SLEEQ to evaluate the cytosolic delivery of a range of widely studied cell-penetrating peptides (CPPs) fused to a model protein. We demonstrate that positively charged CPPs enhance cytosolic delivery as a result of increased non-specific cell membrane association, rather than increased endosomal escape efficiency. These findings transform our current understanding of how CPPs increase cytosolic delivery. SLEEQ is a powerful tool that addresses fundamental questions in intracellular drug delivery and will significantly improve the way materials are engineered to increase therapeutic delivery to the cytosol.

Indexed as

Cell Line, TumorCell MembraneCell-Penetrating PeptidesCell SurvivalCytosolEndosomesGene ExpressionGreen Fluorescent ProteinsHumansLuciferasesLuminescent MeasurementsMass SpectrometryRecombinant ProteinsSensitivity and SpecificityCell-Penetrating PeptidesGreen Fluorescent ProteinsLuciferasesRecombinant Proteins

Identifiers

PMID34140497
PMCPMC8211857
OpenAlexW3169543338

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.