SCOUT® technology for viral vector upstream development
Our SCOUT® technology has been successfully used to substantially increase cell density of diverse viral vector packaging cell lines, resulting in increased vector yields. The SCOUT® technology has also been used to rapidly optimize important vector production parameters, such as best time of harvest, optimal multiplicity of infection (MOI), and optimal genome packaging in culture. To deploy our SCOUT® technology, we have developed optimized protocols for diverse (packaging) cell lines for growth in mini bioreactors, including modified and parental HEK293 cells (for AAV, adenoviral and lentiviral vectors), and Vero cells (for measles and VSV vectors). As such, we have developed standard upstream processes for different vector systems, which we use as starting point to develop a more product-specific process. For instance, for adenoviral vectors we are keenly aware of, and able to exploit the differences between the different serotypes (e.g. human-, rhesus macaque-, chimpanzee-derived) as they can substantially vary in the number of virus particles produced per cell, as well as the ratio of infectious particles versus total virus particles per cell. These parameters also hold true for AAV vectors. We have a panel of GMP-compliant production media that, in conjunction with our SCOUT® system, facilitates the rapid assessment of vector yield under different conditions. One of the great advantages of our SCOUT® technology, in addition to speed, cost-reduction, and versatility, is its scalability. We have shown that optimal upstream parameters identified from our SCOUT® experiments can be seamlessly extrapolated to larger scale bioreactors.
SCOUT® technology for viral vector downstream development
The cell culture capabilities that are part of the SCOUT® technology are matched with high-throughput purification technology. Purification is performed using commercially available 96-well plates, spin-traps and spin-filters, which are packed in-house with various resins to generate custom-made, product-specific, high-throughput purification tools when necessary. High-throughput screening of novel resins to identify binding and elution (using 96-well plates or spin-traps) is part of our repertoire to quickly develop reliable protocols for pharmaceutical grade purification. Using SCOUT® technology, we have developed robust purification processes suitable for a wide range of vectors including adenoviral vector serotypes and the chimeras thereof (human, chimpanzee, rhesus macaque), and for AAV serotypes (AAV1, AAV2, AAV8, AAV9). Naturally, the SCOUT® technology is backed by a wide range of qualified assays ensuring in-process control, anchoring SCOUT® technology as a complete laboratory tool for the rapid and robust development of manufacturing protocols for viral vectors.