Development of a Scalable Viral Vector Upstream Process for Gene Therapy : rAAV-8 Production by Transient Transfection of HEK-293 Cells in iCELLis ® Bioreactor

Today, gene therapy offers perspectives for a wide range of incurable genetic disorders and industrialization of viral vector production becomes a key challenge for the biotechnology industry. In this context, Généthon and Pall combined their respective expertise to assess the single-use iCELLis fixed bed bioreactor system for viral vector production. The choice of the iCELLis system was driven by process automation and control via single-use sensors, reduced footprint and capital investment, and ease of process scale-up. The iCELLis bioreactor is a fully-integrated, high-cell density bioreactor designed to simplify processes involving adherent cells by combining the advantages of single-use technologies with the benefits of a fixed-bed system. The fixed bed provides a 3D environment with low shear stress resulting in very high cell densities and high productivity. iCELLis technology can be used at bench-scale (0.5 to 4 m2) and manufacturing-scale (66 to 500 m2). Fixed-bed height remains constant as scale increases leading to linear scalability between the iCELLis Nano and iCELLis 500 bioreactors (Figure 1). Généthon is interested to move forward in their clinical trials with a scalable high-capacity and cost efficient process with the intention to commercialize in the coming years affordable gene therapy products for rare diseases.