Reliable and scalable procedures for the isolation and loading of extracellular vesicles

Introduction

Exosome-based therapies are among the hottest topics in biomedical research, driven by the unique properties of exosomes regarding stability, low immunogenicity, prolonged circulation, and especially, selective targeting. In 2022, over 50 clinical trials using exosomes for therapy were underway, in diseases ranging from cancer to diabetes to central nervous system disorders.

Challenges in Exosome Research

However, both current research on exosomes and their future translation into clinical therapies are hindered by two significant problems.

Isolation of Exosomes

The first issue is the isolation of exosomes (and of extracellular vesicles in general), a highly challenging task due to:

1. The high complexity of the body fluids that contain them.
2. The delicate nature of exosomes themselves: soft entities of 50-150 nm whose membrane is responsible for key properties and must be preserved.

Ultracentrifugation, the standard isolation method, has clear limitations:

• Low yields
• Impurity of the products
• Damage to exosomal membranes due to long processing times at high g

While numerous alternatives have been commercialized (size, affinity, and precipitation-based methods), these issues remain unsolved.

Loading of Therapeutic Agents

The second problem relates to the loading of therapeutic agents (nanoparticles, drugs, siRNA, miRNA) into exosomes without damaging their membranes, another challenge without a solution today.

Proposed Solutions

LABORIOUS leverages the experience gained in AdG CADENCE to propose innovative solutions.

Innovative Techniques

1. A novel tangential filtration procedure will segregate exosomes by size, removing impurities and minimizing pressure-induced membrane damage.
2. A pioneering continuous electroporation system will provide unprecedented control, allowing the loading of therapeutic cargo with minimal membrane disruption.

Results will be closely monitored for patenting and commercialization, in collaboration with an industrial observer.