Optimization of HEK-293S cell cultures for the production of adenoviral vectors in bioreactors using on-line OUR measurements

J. Gálvez, M. Lecina, C. Solà, J. J. Cairó, F. Gòdia

Producción científica: Artículo en revista indizadaArtículorevisión exhaustiva

25 Citas (Scopus)

Resumen

The culture of HEK-293S cells in a stirred tank bioreactor for adenoviral vectors production for gene therapy is studied. Process monitoring using oxygen uptake rate (OUR) was performed. The OUR was determined on-line by the dynamic method, providing good information of the process evolution. OUR enabled cell activity monitoring, facilitating as well the determination of the feeding rate in perfusion cultures and when to infect the culture. Batch cultures were used to validate the monitoring methodology. A cell density of 10×10 5cell/mL was infected, producing 1.3×10 9 infectious viral particles/mL (IVP/mL).To increase cell density values maintaining cell specific productivity, perfusion cultures, based on tangential flow filtration, were studied. In this case, OUR measurements were used to optimize the dynamic culture medium feeding strategy, addressed to avoid any potential nutrient limitation. Furthermore, the infection protocol was defined in order to optimize the use of the viral inoculum, minimizing the uncontrolled release of particles through the filter unit mesh. All these developments enabled an infection at 78×10 5cell/mL with the consequent production of 44×10 9IVP/mL, representing a cell specific productivity 4.3 times higher than for the batch culture.

Idioma originalInglés
Páginas (desde-hasta)214-222
Número de páginas9
PublicaciónJournal of Biotechnology
Volumen157
N.º1
DOI
EstadoPublicada - ene 2012
Publicado de forma externa

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