SynBac: Designer Baculovirus Genome for Drug Discovery

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Deepak Balaji Thimiri govinda Raj, Anne-Claude Gavin, Toby Gibson, Imre Berger

European Molecular Biology Laboratory, France

Synthetic biology is a new and exciting research field of intense activity, profoundly affecting our perception of the way living organisms work, and the realization of their genetic programs. Synthetic biology encompasses many different methodologies and disciplines, combining approaches from molecular biology, biotechnology and engineering with the objective to design and construct new biological functions and systems which are not found in nature. Our laboratory has developed MultiBac, a technology for producing eukaryotic multi-protein complexes in previously unattainable quantity and quality, catalyzing progress in many areas of the life sciences. MultiBac has become the technology for multi-protein complex production, and already has been distributed close to 500 laboratories world-wide. MultiBac relies on a baculoviral genome from AcMNPV. When developing MultiBac, we engineered this genome by deleting proteolytic and apoptotic activities, applying classical gene-deletion approaches, thus improving the quality of recombinant protein significantly. MultiBac was first mainly to produce high-quality sample for structural biology. More recently, applications of MultiBac emerged that used modular and iterative modification of the genome for wide range of applications including gene therapy or glycoengineering of human therapeutic proteins. Currently, all these applications rely on baculovirus genome (~133 kb) derived from wild-type AcMNPV. This genome has been intensively researched. Genes that are essential for propagation in cell culture and genes which are detrimental for foreign protein production were delineated. beneficial alterations to the genome by classical techniques require currently an excessive effort by specialists. Therefore, it is not possible to fully exploit the vast potential of the baculovirus system to-date. We propose to completely reverse the methodology by using synthetic biology approach. By applying synthetic biology techniques, we aim to completely rewrite, rebuild and improve the baculovirus genome to provide customized engineered surrogates that are tailor-made to fulfill particular needs in academic and industrial R&D.