Evidence map›Paper›PMID 31611380›Full record

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

Cytosolic delivery of inhibitory antibodies with cationic lipids.

Hejia Henry Wang, Andrew Tsourkas

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 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Article
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  11. Article
  12. Review
  13. Lipid Nanoparticle Delivery of Small Proteins for PotentACS applied materials & interfaces · 2023
    Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Coiled coil exposure and histidine tags drive function of an intracellular protein drug carrier.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Article
  19. Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  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

2 authors at 1 institution in 1 country.

Hejia Henry WangGraduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA 19104.
Andrew TsourkasDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104 atsourk@seas.upenn.edu.
University of Pennsylvania · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
Modular approach for the delivery of antibodies into the cytoplasm of cellsR01CA241661 · NCI · UNIVERSITY OF PENNSYLVANIA · PI TSOURKAS, ANDREW · 2019 to 2023
$1.8M
Engineering antibodies for intracellular targetingF30CA221385 · NCI · UNIVERSITY OF PENNSYLVANIA · PI WANG, HEJIA HENRY · 2017 to 2019
$113k
NCI NIH HHS F30 CA221385NCI NIH HHS P30 CA016520NCI NIH HHS R01 CA241661
6 · The paper itself

Abstract

Antibodies can be developed to directly inhibit almost any protein, but their inability to enter the cytosol limits inhibitory antibodies to membrane-associated or extracellular targets. Developing a cytosolic antibody delivery system would offer unique opportunities to directly inhibit and study intracellular protein function. Here we demonstrate that IgG antibodies that are conjugated with anionic polypeptides (ApPs) can be complexed with cationic lipids originally designed for nucleic acid delivery through electrostatic interactions, enabling close to 90% cytosolic delivery efficiency with only 500 nM IgG. The ApP is fused to a small photoreactive antibody-binding domain (pAbBD) that can be site-specifically photocrosslinked to nearly all off-the-shelf IgGs, enabling easy exchange of cargo IgGs. We show that cytosolically delivered IgGs can inhibit the drug efflux pump multidrug resistance-associated protein 1 (MRP1) and the transcription factor NFκB. This work establishes an approach for using existing antibody collections to modulate intracellular protein function.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsBiological TransportCell LineCell MembraneCytosolHEK293 CellsHumansImmunoglobulin GLipid MetabolismModels, BiologicalNF-kappa BStatic ElectricityATP-Binding Cassette, Sub-Family C ProteinsImmunoglobulin Gmultidrug resistance-associated protein 1NF-kappa Bantibodycytosolicintracellularpenetratingprotein delivery

Identifiers

PMID31611380
PMCPMC6825285
OpenAlexW2980403657

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.