Modifying cells to release exosomes overexpressing an RNA or a protein to enhance its natural therapeutic activity
Mother cell source
The selection criteria for the EV cell source can be divided in two categories: i) the extracellular vesicle intrinsic properties, in line with their therapeutic activity, and ii) the cell line characteristics associated to their robustness for large production.
Each extracellular vesicle type is associated to endogenous biological properties, that will drive their pharmaceutical effect. It is related to their biomolecular content, and their physical properties. The cell source also directly influences the ability to produce a large extracellular vesicle quantity, which is important in terms of collected doses. Different cells secrete very different quantities of EVs in the same culture conditions. In any cases, cells must be expanded widely, over multiple passages. It means that their availability, together with their stability during the scale-up is essential. Finally, modifying cells with stable transfection for example enables the generation of exosomes overexpressing an RNA or a protein to enhance its natural therapeutic activity.
Once the type of cell sourcing for extracellular vesicles has been selected, it remains to decide to work with primary cell line, which will be closer to the physiological properties but available only during a limited time, or with immortalized cells, with some safety risks and a potential derivation of the cell line. But immortalization allows a phenotypic and genotypic stability, increases the amplification potential, and batch consistency. At the same time, it will reduce costs associated to multiple master cell bank validations. Immortalization was not possible for cell therapy due to safety concerns, but with extracellular vesicles, it becomes straightforward.
EVerZom platform is built on four blocks from the cell source to the formulated exosome drug
