From mathematical models to bioprocess optimization

Oeiras, 07.04.10

Researchers at the Animal Cell Technology Unit described a combined experimental and modeling approach to environmentally manipulate the metabolism of insect cells for increased production of baculovirus vectors with potential application in human gene therapy. The work is featured in the cover of the journal Metabolic Engineering. 

Despite its wide use for recombinant protein production and its increased interest for other biomedical applications, the industrial production of baculovirus expression vectors has been hampered by the observed loss of productivity in high host-cell titers. Since traditional attempts had only modest or cost-ineffective improvements, researchers decided to look at how the infection process impacts the intracellular metabolic fluxes and how culture manipulation could affect the whole process.

It is clear that different culture conditions correspond to different metabolic states and concomitantly to different productivities. But predicting the system’s productivity for a given set of culture parameters is not so straightforward. Nor is it optimizing it. This is why, bioengineers resort to mathematical methods, such as Metabolic Flux Analysis. Using this method, researchers at the Animal Cell Technology Unit  have previously identified the energetic state of baculovirus-infected insect cells as a reliable sensor of the system’s productivity. In this work, researchers go a step further and show that it is possible to manipulate the metabolic pathways of the insect cells, trough medium supplementation, to boost recombinant baculovirus production at high cell density.

Original Article

Metabolic Engineering 12 (2010) 39–52, doi:10.1016/j.ymben.2009.08.008

Improving baculovirus production at high cell density through manipulation of energy metabolism

Nuno Carinhas, Vicente Bernal, Francisca Monteiro, Manuel J.T. Carrondo, Rui Oliveira, Paula M. Alves