AAV PRocess INTensification with 3D printed materials
Significant advances in the increased therapeutic efficacy of viral vectors for gene delivery have stimulated a major interest in the development and commercialization of such therapeutic products. Of the gene therapy products in development, recombinant Adeno-Associated Virus (AAV) based vectors are currently the most widely used. The promise and potential of this technology are perhaps best exemplified by the market authorization of three commercial gene therapies – Glybera, Luxturna® and, most recently, Zolgensma®. However, the high demand for these vectors that can go up to 5E20 viral particles per year is one of the biomanufacturing bottlenecks representing a major challenge hampering clinical-to-market transition of these products. PRINTƎD uses affinity ligands in 3D printed devices to produce customized adsorptive materials that will contribute to the available toolbox for AAV downstream processing. For this purpose, affinity ligands will be immobilized to 3D printed devices (i3DC) and the ligand density, capacity, and the operating conditions that ensure binding and release of AAV will be optimized. Furthermore, intensification of the purification process by continuously capturing AAV directly from the bioreactor vessel (2L and a proof-of-concept 10 L scale), will allow the reduction of the number of purification steps, thus improving productivity and reducing cost of goods. Overall, PRINTƎD is an intensified purification framework that can cope with the different manufacturing scales. The generation of post-modification surfaces, particularly 3D printed structures, that can specifically address the specificities of AAVs has never been reported and can be a viable scalable purification strategy. In that regard, its success might imply a fast transition to a novel technology with reduced cost and thus to a new paradigm of production of new vaccines and gene therapy products.