By Evercyte GmbH
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New study confirms effectiveness of unique Evercyte CD81 antigen recognition technology
Vienna, Austria: – A new research study has found new evidence for the effectiveness of a technology developed by Innovative biotech manufacturer Evercyte GmbH for engineering of extracellular vesicles (EVs) using the extracellular loop domain of CD81) to allow specific targeting of antigens.
Evercyte has applied for patents on the technology of antigen recognition via antigen binding marker proteins of EVs (patent application PCT/EP2019/071825).
Enhancing extracellular vesicle uptake
The study ‘An engineered CD81-based combinatorial library for selecting recombinant binders to cell surface proteins: Laminin binding CD81 enhances cellular uptake of extracellular vesicles’ was carried out by a team led by Gordana Wozniak-Knopp from the Institute of Molecular Biotechnology at University of Natural Resources and Life Sciences (BOKU) in Vienna. Other colleagues were drawn from the Austrian Center for Industrial Biotechnology (ACIB), BOKU’s Christian Doppler Laboratory for Innovative Immunotherapeutics, along with Vienna’s Ludwig Boltzmann Institute for Traumatology – the research center in cooperation with AUVA and the Interdisciplinary Nanoscience Centre (iNANO) at Aarhus University in Denmark.
A key developer of the CD81-based technology, Dr. Johannes Grillari, took part in an academic capacity, representing both BOKU and the Ludwig Boltzmann Institute for Traumatology with his role as Evercyte co-founder and scientific advisor acknowledged in the published paper.1
Engineering CD81 into antigen recognition scaffold
The study set out to examine the effectiveness of the technique at the heart of the new technology; leveraging the innately overrepresented EV surface protein and hallmark surface marker CD81 into an antigen-recognition scaffold by developing yeast libraries displaying mutant variants of the large extracellular loop of CD81 as binders. For the study, human placental laminin was used as model target, with specific interactions confirmed in a mammalian display system. Derived sequences were reformatted to full-length CD81 and expressed in EVs produced by HeLa cells.
The team found that EVs examined for the presence of the recombinant protein exhibited signs of enhanced uptake into laminin-secreting mammalian cell lines.
Target-directed drug delivery
“To our knowledge, this is the first example of harnessing an EV membrane protein as mediator of de novo target antigen recognition via in vitro molecular evolution, opening horizons to a broad range of applications in various therapeutic settings,” the authors concluded.
Dr. Johannes Grillari commented: “This study confirms that we have succeeded in developing a method that allows engineering of extracellular vesicles based on CD81 extracellular loop domain to allow specific targeting of antigens, for more effective targeted drug delivery.”
“This has important implications for companies and researchers interested in tissue targeting, who now know that we can offer enhanced engineering of EVs,” Dr. Grillari added.
- Vogt, S., Bobbili, M.R., Stadlmayr, G., Stadlbauer, K., Kjems, J., Rüker, F., Grillari, J., Wozniak- Knopp, G. ‘An engineered CD81-based combinatorial library for selecting recombinant binders to cell surface proteins: Laminin binding CD81 enhances cellular uptake of extracellular vesicles’, J Extracell Vesicles 2021 Sep;10(11):e12139: DOI: 10.1002/jev2.12139.
Evercyte is the leading provider of immortalized human primary-like cells (‘telomerized cells’) as well as novel production cell lines for extracellular vesicles and is the partner of choice for innovative cell-based assays in the field of pharma, biotech, or cosmetic industries.
The core technology used for the establishment of these highly relevant human cell lines relies on the reactivation of the human telomerase enzyme. Besides customer-tailored cell line development as a one-stop shop, Evercyte is steadily expanding its catalog of readily available cell lines for the production of extracellular vesicles from mesenchymal stem cells using different tissues including Wharton’s Jelly, adipose tissue, bone marrow, and placenta.
By providing native extracellular vesicles from mesenchymal stem cells and targeting extracellular vesicles Evercyte will make a significant contribution to the development of new therapeutic approaches.
Founded in 2011, the Vienna-based company successfully pioneered the development of tools and know-how necessary for the establishment of standardized high-throughput in vitro bioassays as well as relevant cell models and cell factories.
Click on An engineered CD81-based combinatorial library for selecting recombinant binders to cell surface proteins to read the study.