Engineering Viral Vector Biomanufacturing for Gene Therapy

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Gene therapies utilise engineered, non-pathogenic viruses (such as adeno-associated virus, AAV) as vehicles to deliver therapeutic genes to the human body that can correct genetic changes underpinning disease. This approach is potentially applicable to multiple organs of the human body, and the advanced therapies have been successfully studied in clinical trials for the treatment of, for example, a wide variety of genetic disorders and cancers. New gene therapies are beginning to be approved for use in the clinic. In 2019 73% of all viral vector clinical trials were based in the UK, 89% of which utilised AAV. It is estimated that the market for gene therapies will reach 36B USD by 2027 with a compound annual growth rate of 36%.However, viruses such as AAVs are complex molecular assemblies of numerous components which are difficult to manufacture, relying on introduction of synthetic genetic components into mammalian cells in controlled culture processes for virus manufacture, followed by purification and analysis of product quality. Low product yields and production of viruses lacking the therapeutic gene payload are endemic problems for manufacturing process development; current UK facilities for manufacturing viral vectors suitable for human treatment cannot meet demand, thus seriously hindering the translation of exciting gene therapies into clinical trials. New technology for intensified production of high quality viral gene therapies is urgently required.This project is within the scope of the EPSRC themes Manufacturing the Future and Healthcare Technologies. With respect to the latter, Developing Future Therapies is an identified. grand challenge.