Among viral delivery systems, recombinant adeno-associated viruses (AAVs) have become the preferred vector for gene therapy because of their high transduction efficiency, safety profile, and long-term gene expression. The increasing number of gene therapy programs has increased the demand for these viral vectors in a clinical setting despite recent setbacks. However, AAV production in a GMP setting at the required yield and purity needed to meet expanding clinical demand remains a hurdle with current production systems and global capacity.
Transient transfection of DNA into HEK293 cells is the most widely utilized method to generate the target vector, but one limitation is the scalability of adherent HEK293 cell lines. To increase viral titers, manufacturers are shifting towards HEK293 cell lines grown in suspension to increase volumetric productivity. The cell culture media is one bioprocessing parameter that can modulate the productivity of a given cell line since it must supply the energy and nutrients required for survival and functionality. Since AAV production is not standardized, there are a variety of HEK293 clones used in different programs, each with their own optimal nutritional profile. Therefore, one strategy to increase cell expansion and vector production is to optimize the cell culture media. However, this can be a time-consuming and complex endeavor – even the simplest media formulations can have upwards of 20+ components – which may not fit within the condensed timelines faced by gene therapy developers.
To help expedite the process of media optimization, Thermo Fisher Scientific offers a ready-to-use Gibco™ Viral Vector HEK Media Panel to enable the screening of a set of formulations suitable for a broad range of HEK293 cell lines. Additionally, developers can leverage the years of media development expertise from the inhouse technical team, who can provide input on experimental design and support throughout the process. The targeted media panel encompasses a broad range of nutrient profiles that provides more formulation diversity than simply screening catalog media. This diversity maximizes and streamlines media evaluation to quickly narrow in on a formulation that drives productivity and quality for the target cell line.
Once a formulation is identified, customization can be done to improve performance even further. An added benefit to working with an established media supplier is that once a formulation has been identified that is suitable for the cell line and intended bioprocess, it can be easily transferred to the Gibco™ Rapid Prototyping facility or the cGMP facility for manufacturing to support the volume and quality needs as gene therapies transition from clinical development to commercialization. The ability for gene therapy developers to optimize bioprocessing parameters to increase viral titers can translate to cost and time savings that can ultimately help bring these therapies to market sooner.