BIOSCALE

Recombinant Adeno-Associated Virus (AAV) are viral vectors of choice for in vivo gene therapy with five products currently approved in the market. However, the manufacturing process to produce large amounts of AAV vectors remains a major challenge.

The BIOSCALE project aims to improve the entire large-scale AAV biomanufacturing chain, from intensive cell suspension culture to improved vector purification systems. At the end of the project, we aim to increase AAV production yields by at least 20 to 100-fold while meeting regulatory standards for product safety and activity.

During this project, we will generate proprietary “super cell clone(s)” for the generation of AAV vectors in mammalian HEK293 suspension cells with higher yields and improved quality. To select such clone(s), we will develop in process control methods to monitor cell state during the bioreactor culture using holographic imaging. In order to increase process productivity, we will also develop a new purification method to reduce the number of purification steps and process time, and as a consequence significantly reduce costs while improving the final quality of vectors. The compliance of these innovative and complementary upstream and downstream developments to Good Manufacturing Practices (GMP) guidelines will be performed during all steps of the project, in particular during the upscaling phase to de-risk a future industrial transfer.

This project is of primary importance for the French bioproduction landscape of AAVs and will enable the emergence of disruptive new technologies that can be patented and industrialized. In addition, several technologies developed during this project may have applications for the bioproduction of other biotherapies (e.g. recombinant proteins, therapeutic antibodies, vaccines, etc.).