Data-driven experimental approach to increase transfection efficiency and prolonging vector production in transient systems

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The production of lentiviral vector (LVV) has been critical for the emergence of ex vivo gene-modified cellular therapies, such as chimeric antigen receptor T cells (CAR-T). However, it is widely recognised that there are global limitations on both capacity and capability. One of the key manufacturing challenges for LVV is the limitations around the transfection process and enabling prolonged production. The project is focused on developing a data-driven experimental approach to achieve an optimal bioprocess which results in higher lentiviral (LV) transfection efficiencies and/or prolonged LV production compared to the current gold standard process.The approach this project will adopt is to combine the power of high-throughput experimental studies in combination with machine-learning based approaches to identify the optimal factors for improved transfection efficiency. Following the systematic ranking of key variables and the establishment of the design space, experimental studies will be undertake to explore the design space of factors. Throughout the course of the experimental work, periodic scale-up work will be undertaken to confirm scalability of the small-scale studies and findings. Moreover, investigations will be undertaken to asses the impact the upstream optimisation on downstream processing.This project has potential to significantly enhance and improve the production of LVV and ensure that large quantities of functional vector are made available for the next generation of advanced therapeutics. This project is aligned closely to EPSRC's Manufacturing the Future research theme which focuses on researching and developing high-value manufacturing capability and capacity for the UK.