10101911Next generation high-yield producer platform for cell and gene therapy viral vectors and other complex biologics.ActiveCollaborative R&DInnovate UKCell and gene therapies are promising treatments for several unmet medical needs. Most of these therapies rely on viral vectors as the delivery tool for cell modification. HEK-293 cell line is the most used platform for the manufacturing of cell and gene therapy viral vectors that have achieved successful clinical data and regulatory approval for commercialization. However, the production capacity of this platform is still inefficient to meet the current and growing future demand for viral vectors which leads to the need for large volume bioreactors and high manufacturing costs. Several attempts described in literature to genetically modify HEK-293 cells to improve viral vector titers have resulted in modest improvements in productivity. In this project, we aim to increase viral vector productivity at least 50-100 folds higher by the genetic modification of the 293 cell line targeting genes with crucial role in viral vector production and quality. For that, functional genomics analysis will be used for the gene identification instead of a comparison gene by gene approach as previous attempts. By using functional genomic analysis, the focus will not only be on the genomic but also a combination of epigenomics, transcriptomics, proteomics and metabolomics. As a result, a HEK-293 cell line adapted to serum-free media and in suspension growth will be genetically modified using CRISPR gene editing, At the same time, within the frame of this project, a single plasmid technology will be developed to achieve process cost-reduction and simplicity. In order to support the process development and the screening of the higher producer clones, a fully automated instrument will be developed for virus detection. Furthermore, the manufacturing process of the high-producer cell line will be established and validated at large scale bioreactors. The successful development of this project will deliver a highly productive viral vector manufacturing platform able to provide high yields and high-quality products in a cost-effective manner which will ultimately be at the service of the biotech community to accelerate the clinical translation and affordability of advanced therapies.