Trinity researchers drive research on extracellular vesicle towards standardised methods for quality assessment

The interlaboratory research work driven by the EXPERT partner Trinity College Dublin (Prof Adriele Prina-Mello, Laboratory for Biological Characterisation of Advanced Materials (LBCAM), Trinity Translational Medicine Institute)) jointly with the European Commission Joint Research Laboratory, SINTEF industry and instrumentation developers IZON and NanoFCM has recently published on the prestigious Journal of Extracellular Vesicles and can be found as open access for download here:

https://onlinelibrary.wiley.com/doi/full/10.1002/jev2.12052

The work originated as part of the EXPERT project under the objectives of developing clinically relevant advance therapeutics based on extracellular vesicles (EV) or mRNA targets as future nanomedicines. One of the main challenges faced resides on the measurement of physicochemical properties of the biological sample which is a known issue impacting the production and isolation methods for both EV and nanomedicines. The community is gradually becoming aware of the need to combine multiple orthogonal techniques to perform a robust characterization of complex biological samples. The published paper tackle with the repeatability and reproducibility of two of the three pillars determining the critical quality attribute characterization of EV and nanocarrier (as nanoparticle and liposomes): sizing and concentration measurement. In this study, the performance of measuring the concentration of particles in the size range of 50–300 nm with complementary techniques is thoroughly investigated in a step‐by step approach of incremental complexity. The six applied techniques include multi‐angle dynamic light scattering (MADLS), asymmetric flow field flow fractionation coupled with multi‐angle light scattering (AF4‐MALS), centrifugal liquid sedimentation (CLS), nanoparticle tracking analysis (NTA), tunable resistive pulse sensing (TRPS), and high‐sensitivity nano flow cytometry (nFCM). The results presented shed some light into the requirements for the complex characterization of biological samples, as this is a critical need for quality assurance by the EV and regulatory community. Such efforts go with the view to contribute to both, set‐up reproducible and reliable characterization protocols, and comply with the Minimal Information for Studies of Extracellular Vesicles (MISEV) requirements.

“We are delighted of the results of this large and complex study published in the official journal of the International Society of Extracellular Vesicles, where we are able to share our approach, we have developed for the accurate characterisation of nanometre size complex samples” comments Prof. Prina-Mello, corresponding author in the paper and EXPERT project partner. “We hope our work will be widely adopted and followed as practical methodological approach for the future measurement and quality control of advanced therapy medicinal products (ATMPs) and nanomedicines.”

The EXPERT project is working at expanding such complex characterisation approach for measuring the quality and critical attributes of ATMPS and nanomedicines based on EVs and mRNA.

“What we find in EXPERT is that the efficiency of any mRNA therapeutic is critically dependent on the characteristics of the nanoparticle in which we encapsulate it. To be able to measure these critical attributes in a standardized manner, also for complex nanoparticles like extracellular vesicles, is an important step forward for our consortium but also the wider nanomedicine and extracellular vesicle community” says Prof Raymond Schiffelers, coordinator of EXPERT and professor of nanomedicine at University Medical Center Utrecht.

About LBCAM:
The Laboratory for Biological Characterisation of Advanced Materials (LBCAM) is the innovative centre for material characterisation, biological interaction models development and pre-clinical assessment of biomedical solution or medical technologies for academic research groups and industry. https://www.tcd.ie/ttmi/facilities/lbcam/about-us.php

For any further information please contact:
Dr. A. Prina-Mello