Improving the production and quality of lentivirus for the transduction of haematopoeitic stem cells via a perfusion culture process

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Scalable and consistent production of LV is critical to ensure sufficient supply of high-quality vector for gene therapies and gene-modified cell therapies. The focus of the project is to optimise lentiviral vector (LV) production through the investigation of perfusion and the establishment of a high-throughput, scalable suspension platform for suspension-adapted HEK cells.The process conditions established in the small scale stirred-tank bioreactor systems (100-250 mL) will be validated in larger-scale stirred-tank bioreactor system (up to 5L). The LV produced will be used to transduce the target cells of interest (hematopoietic stem cells - HSCs). Specifically, this project will build on previous work undertaken at CSL developing a suspension-adapted HEK cell line and establish a robust perfusion process following large-scale DoE studies investigating the key process parameters. Work will begin by investigating a range of platforms to establish a suitable high-throughput, small-scale suspension platform for the LV production studies. Once established, a perfusion process will be developed and the LV produced will be tested for functionality on the target haematopoietic stem cells.This aligns to the EPSRC's Healthcare Technologies and Manufacturing the Future Themes, specifically the 'Developing Future Therapies' and '21st century products' Grand Challenges.