Quantification of protein cargo loading into engineered extracellular vesicles at single-vesicle and single-molecule resolution.


Journal

Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479

Informations de publication

Date de publication:
08 2021
Historique:
received: 14 10 2020
revised: 20 06 2021
accepted: 13 07 2021
entrez: 11 8 2021
pubmed: 12 8 2021
medline: 12 8 2021
Statut: ppublish

Résumé

Extracellular Vesicles (EVs) have been intensively explored for therapeutic delivery of proteins. However, methods to quantify cargo proteins loaded into engineered EVs are lacking. Here, we describe a workflow for EV analysis at the single-vesicle and single-molecule level to accurately quantify the efficiency of different EV-sorting proteins in promoting cargo loading into EVs. Expi293F cells were engineered to express EV-sorting proteins fused to green fluorescent protein (GFP). High levels of GFP loading into secreted EVs was confirmed by Western blotting for specific EV-sorting domains, but quantitative single-vesicle analysis by Nanoflow cytometry detected GFP in less than half of the particles analysed, reflecting EV heterogeneity. Anti-tetraspanin EV immunostaining in ExoView confirmed a heterogeneous GFP distribution in distinct subpopulations of CD63

Identifiants

pubmed: 34377376
doi: 10.1002/jev2.12130
pii: JEV212130
pmc: PMC8329990
doi:

Substances chimiques

Recombinant Fusion Proteins 0
Tetraspanins 0
Green Fluorescent Proteins 147336-22-9

Types de publication

Journal Article

Langues

eng

Pagination

e12130

Informations de copyright

© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

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Auteurs

Andreia M Silva (AM)

Discovery Biology Discovery Sciences BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden.

Elisa Lázaro-Ibáñez (E)

Discovery Biology Discovery Sciences BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden.
Advanced Drug Delivery Pharmaceutical Sciences BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden.

Anders Gunnarsson (A)

Structure and Biophysics Discovery Sciences BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden.

Aditya Dhande (A)

NanoView Biosciences Boston Massachusetts USA.

George Daaboul (G)

NanoView Biosciences Boston Massachusetts USA.

Ben Peacock (B)

NanoFCM INC. Nottingham UK.

Xabier Osteikoetxea (X)

Discovery Biology Discovery Sciences BioPharmaceuticals R&D AstraZeneca Alderley Park UK.

Nikki Salmond (N)

Discovery Biology Discovery Sciences BioPharmaceuticals R&D AstraZeneca Alderley Park UK.

Kristina Pagh Friis (KP)

Advanced Drug Delivery Pharmaceutical Sciences BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden.

Olga Shatnyeva (O)

Discovery Biology Discovery Sciences BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden.

Niek Dekker (N)

Discovery Biology Discovery Sciences BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden.

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