We maintained a strategic focus on cell culture in suspension and serum free medium using HEK-293 as a host for the expression of recombinant proteins and viral vectors. HEK-293 central metabolism was successfully characterized using a metabolic flux analysis based on an original metabolic model. Findings led to identification of limiting pathways that are being genetically modified in order to improve the metabolism during growth and more importantly during product expression. Research on the characterization of the infection/transfection kinetics in suspension and serum free cultures contributed to the establishment of HEK-293 cells as an important industrial platform for recombinant proteins and viral vectors using novel proprietary processes.
A multidisciplinary and multidimensional approach led to significant improvements in the performance of the insect cell-baculovirus system at very high cell density, by integrating a solid knowledge on the baculovirus viral life cycle and the dynamics of interaction with the producing cell line focusing on the physiology and metabolism of the cell populations. As a consequence, ten-fold improvement in the yields was achieved using fed-batch culture methods. The application of the technology is rapidly expanding to the production of not only recombinant proteins but also virus-like particles for vaccinations and new generation of viral vectors for gene therapy applications. This technological advancement is the basis of multiple collaborations with key players in the field of vaccines and gene therapy.