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Related Experiment Video

Updated: Jul 12, 2025

Directed Assembly of Elastin-like Proteins into defined Supramolecular Structures and Cargo Encapsulation In Vitro

Directed Assembly of Elastin-like Proteins into defined Supramolecular Structures and Cargo Encapsulation In Vitro

Published on: April 8, 2020

Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled

Alena Ivanova¹, Lukas Badertscher², Gwen O'Driscoll^1,3

¹Discovery Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, Mölndal, 431 50, Sweden.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)

|October 22, 2023

Summary

This summary is machine-generated.

Biochemical engineering enhances extracellular vesicles (EVs) for targeted drug delivery. Engineered EVs show improved cargo loading, specific cell targeting, and are well-tolerated in vivo, advancing their use as therapeutic vehicles.

Keywords:

exosomes extracellular vesicles genetic engineering protein loading targeting

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Published on: July 25, 2022

Area of Science:

Biochemical Engineering
Nanomedicine
Drug Delivery Systems

Background:

Targeted delivery of therapeutic agents is a significant challenge in medicine.
Extracellular vesicles (EVs) show promise as natural drug delivery vehicles.
Engineering EVs can enhance their targeting and cargo-loading capabilities.

Purpose of the Study:

To explore biochemical engineering approaches for repurposing extracellular vesicles (EVs) as targeted drug delivery vehicles.
To improve EV targeting specificity and cargo loading efficiency.
To assess the in vivo safety and efficacy of engineered EVs.

Main Methods:

Surface display of targeting ligands (GalNAc, anti-GLP1 receptor antibody) on EVs using protein anchors (HaloTag, Fc/Fab binding moiety).
Protein engineering strategies to enhance Cre recombinase loading into the EV lumen.
In vitro targeting assays with primary hepatocytes and receptor-overexpressing cells.
In vivo intravenous injection studies in mice to evaluate tolerability and liver toxicity.

Main Results:

Engineered EVs successfully targeted human primary hepatocytes via GalNAc display.
Antibody-decorated EVs enhanced targeting to cells overexpressing the GLP1 receptor.
Improved loading of functional Cre recombinase into EVs was achieved using protein engineering.
Delivered Cre protein demonstrated functionality in cells with endosomal escape enhancement (chloroquine).
Engineered EVs were well-tolerated in mice, showing no detectable liver toxicity.

Conclusions:

Biochemical engineering enables the development of targeted extracellular vesicles for drug delivery.
Surface modification and protein engineering significantly improve EV targeting and cargo delivery.
Engineered EVs represent a safe and effective platform for advanced therapeutic applications.