Gene therapy vector engineering for sustainable manufacture

Project ID: 2531ad1490

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UCL Lead department: Biochemical Engineering

Lead Supervisor: Paul Dalby

Project Summary:

AAV-based gene therapies are typically engineered to improve their clinical potency and safety, which has delivered clinical breakthroughs for some diseases. However, more radical vector engineering will be needed in new products to avoid neutralising immune responses in patients as these vectors become more widely used. Furthermore, current vectors have shockingly poor manufacturing efficiency and stability leading to eye-watering costs (eg. Zolgensma, £1.79m per dose) and poor manufacturing sustainability profiles. AAV is a protein-based viral vector and specific surface regions are often mutated to modify their cell targeting. However, this often negatively impacts on manufacturing yields and storage stability, leading to lower manufacturing sustainability and higher costs to NHS / patients. This project will use our growing database of vector mutations to drive predictive (PLS/ML) models of sequence to manufacturing performance relationships, and then use this to redesign vectors that have simultaneously all the desired clinical and manufacturing properties.