Integrating biological and engineering approaches to maximize the utility of baculoviruses as gene delivery vehicles

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The demand for biologics is increasing at an unprecedented rate. US demand alone for biologics is expected to go beyond $100 billion/year by 2015. Animal cell culture is the major platform for high value biologics production, with Chinese Hamster Ovary cells having dominated the bioprocess industry for many years. Insect cells, however, offer many advantages over mammalian cells. These advantages include: not propagating human or mammalian specific viruses; being grown in suspension culture to high cell densities without the presence of serum in the media - eliminating a potential source of prion and mammalian virus contamination; and, in combination with the baculovirus expression vector system (BEVS), allowing high levels of protein expression. This research program aims to further insect cell culture as an alternative production platform by enhancing the control over protein expression and by enabling a better understanding of insect cell metabolism. Fine control over protein expression will be achieved through the manipulation of genetic promoter sequences. Optimal combinations will lead to the creation of new expression vectors that can be used as platform technologies for the optimal production of biologics. To further enhance the environment used to produce these biologics, metabolomics will be used to refine and expand existing metabolic models of insect cells. With this approach, feeding profiles will be developed for production at high cell densities, leading to greater and more consistent yields of biologics. These advances will come with the training of 9 students: 4 PhD students and 5 undergraduates. These students will become highly qualified in the area of bioprocessing and will be familiar with all aspects of biologics production: from manipulating DNA to product purification.