Evidence map›Paper›PMID 31633910›Full record

ArticleACS chemical biology2019

Cytosolic Delivery of Macromolecules in Live Human Cells Using the Combined Endosomal Escape Activities of a Small Molecule and Cell Penetrating Peptides.

Jason Allen, Kristina Najjar, Alfredo Erazo-Oliveras, Helena M Kondow-McConaghy, Dakota J Brock, Kristin Graham, Elizabeth C Hager, Andrea L J Marschall, Stefan Dübel, Rudolph L Juliano and 1 more

Abstract read
In one paragraph

Article in ACS chemical biology, 2019. 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
–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

23 citing papers in PubMed.

  1. Review
  2. Intracellular delivery of proteins for live cell imaging.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Synthetic Ionizable Colloidal Drug Aggregates Enable Endosomal Disruption.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  10. Characterization of PGuaMolecular pharmaceutics · 2023
    Article
  11. Article
  12. Article
  13. Cell-Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  14. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. 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

11 authors.

Jason AllenDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.ORCID 0000-0002-2461-6980
Kristina NajjarDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.
Alfredo Erazo-OliverasDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.
Helena M Kondow-McConaghyDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.
Dakota J BrockDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.
Kristin GrahamDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.ORCID 0000-0002-6523-7143
Elizabeth C HagerDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.ORCID 0000-0002-1836-1432
Andrea L J MarschallInstitute of Biochemistry, Biotechnology and Bioinformatics , Technische Universität Braunschweig , 38106 Braunschweig , Germany.
Stefan DübelInstitute of Biochemistry, Biotechnology and Bioinformatics , Technische Universität Braunschweig , 38106 Braunschweig , Germany.
Rudolph L JulianoUNC Eshelman School of Pharmacy and UNC School of Medicine , University of North Carolina , Chapel Hill , North Carolina 27599 , United States.
Jean-Philippe PelloisDepartment of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.ORCID 0000-0001-5536-925X

Funding

Mechanisms and optimization of endosomal escape for delivery applicationsR01GM110137 · NIGMS · TEXAS A&M AGRILIFE RESEARCH · PI PELLOIS, JEAN-PHILIPPE · 2015 to 2022
$2.3M
NIGMS NIH HHS R01 GM110137
6 · The paper itself

Abstract

Ineffective cellular delivery is a common problem in numerous biological applications. Developing delivery reagents that work robustly in a variety of experimental settings remains a challenge. Herein, we report how peptides derived from the prototypical cell penetrating peptide TAT can be used in combination with a small molecule, UNC7938, to deliver macromolecules into the cytosol of cells by a simple co-incubation protocol. We establish successful delivery of peptides, DNA plasmids, and a single-chain variable fragment antibody. We also demonstrate that delivery works in hard-to-transfect mammalian cells and under conditions typically inhibitory to cell-penetrating peptides. Mechanistically, UNC7938 destabilizes the membrane of endosomes. This, in turn, enhances the endosome-leakage activity of cell-penetrating peptides and facilitates the endosomal escape of macromolecules initially internalized by mammalian cells via endocytosis. This combined selective membrane-destabilization represents a new chemical space for delivery tools and provides a novel solution to the problem of endosomal entrapment that often limits the effectiveness of reagent-based delivery approaches.

Indexed as

Cell-Penetrating PeptidesCytosolEndosomesHumansMacromolecular SubstancesPyrazinesPyridinesCell-Penetrating PeptidesMacromolecular SubstancesPyrazinesPyridinesUNC7938

Identifiers

PMID31633910
PMCPMC7008471

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.