Evidence map›Paper›PMID 30882208›Full record

ReviewBioconjugate chemistry2019

Trapped! A Critical Evaluation of Methods for Measuring Total Cellular Uptake versus Cytosolic Localization.

Kirsten Deprey, Lukas Becker, Joshua Kritzer, Andreas Plückthun

Abstract readReview
In one paragraph

Review in Bioconjugate chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
–field-weighted citation impact
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

51 citing papers in PubMed.

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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.

Kirsten DepreyDepartment of Chemistry , Tufts University , 62 Talbot Avenue , Medford , Massachusetts 02155 , United States.
Lukas BeckerDepartment of Biochemistry , University of Zurich , Winterthurerstrasse 190 , 8057 Zurich , Switzerland.
Joshua KritzerDepartment of Chemistry , Tufts University , 62 Talbot Avenue , Medford , Massachusetts 02155 , United States.ORCID 0000-0003-2878-6781
Andreas PlückthunDepartment of Biochemistry , University of Zurich , Winterthurerstrasse 190 , 8057 Zurich , Switzerland.ORCID 0000-0003-4191-5306

Funding

Cell Penetration Profiling for BiotherapeuticsR01GM127585 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI KRITZER, JOSHUA A · 2018 to 2022
$1.6M
Translation of Hot Loops into Macrocyclic Inhibitors of Protein-Protein InteractionsR01GM125856 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI KRITZER, JOSHUA A · 2018 to 2021
$1.1M
NIGMS NIH HHS R01 GM125856NIGMS NIH HHS R01 GM127585
6 · The paper itself

Abstract

Biomolecules have many properties that make them promising for intracellular therapeutic applications, but delivery remains a key challenge because large biomolecules cannot easily enter the cytosol. Furthermore, quantification of total intracellular versus cytosolic concentrations remains demanding, and the determination of delivery efficiency is thus not straightforward. In this review, we discuss strategies for delivering biomolecules into the cytosol and briefly summarize the mechanisms of uptake for these systems. We then describe commonly used methods to measure total cellular uptake and, more selectively, cytosolic localization, and discuss the major advantages and drawbacks of each method. We critically evaluate methods of measuring "cell penetration" that do not adequately distinguish total cellular uptake and cytosolic localization, which often lead to inaccurate interpretations of a molecule's cytosolic localization. Finally, we summarize the properties and components of each method, including the main caveats of each, to allow for informed decisions about method selection for specific applications. When applied correctly and interpreted carefully, methods for quantifying cytosolic localization offer valuable insight into the bioactivity of biomolecules and potentially the prospects for their eventual development into therapeutics.

Indexed as

Drug Delivery SystemsBacterial ToxinsBiological TransportCell CompartmentationCell MembraneCell-Penetrating PeptidesCytosolDNA-Binding ProteinsHumansLiposomesNanoparticlesVirionZinc FingersBacterial ToxinsCell-Penetrating PeptidesDNA-Binding ProteinsLiposomes

Identifiers

PMID30882208
PMCPMC6527423

What OpenQuestion holds

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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.