By Anja Rodenbrock, Aziza Manceur, Sophie Broussau, Julia Transfiguracion, Rénald Gilbert, Chun Fang Shen, and Martin Loignon
Volume 23, Open Access (November 2024)
The rapidly growing interest for cell and gene therapies demands the development of robust, scalable, and cost-effective bioprocesses for viral vector production. For the production of lentiviral vector (LVV) at high titers, we have developed an inducible packaging system in suspension HEK293 cells from which we can also generate stable producer cell lines, in serum-free conditions. To evaluate the potential of this platform, we have generated a stable cell line that produces an LVV encoding a green fluorescent protein (GFP) and obtains 1×107 to 1×108 transduction units (TU)/mL at the 4 L, 10 L and 50 L scales. Functional LVV titers were maintained across all scales in bioreactors with different configurations and geometries indicating process robustness. Further, the addition of 10% feed increased the volumetric productivity by 3.5-fold in comparison to batch production, making our platform suitable for large-scale LVV production and showing a real potential for commercial manufacturing.
Citation: Rodenbrock, A.; Manceur, A.; Broussau, S.; Transfiguracion, J.; Gilbert, R.; Shen, C. F.; Loignon, M. Development of a scalable fed-batch bioreactor process for high-titer production of lentiviral vector using an inducible HEK293 producer cell line. BioProcess J 2024, 23. https://doi.org/10.12665/J23OA.Manceur
Posted online November 7, 2024