Optimisation of CHO for Biotherapeutic Manufacture

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Biological drugs (e.g. monoclonal antibodies, MAbs) based on recombinant DNA technology have transformed the treatment of life-limiting diseases including cancer, haemophilia and rheumatoid arthritis. The recent explosive growth in the biologics sector looks set to continue, with growing applications in precision medicine and personalised healthcare, and there are many new complex biologics in the drug discovery pipeline (e.g. bispecific, trispecific, and conjugated MAbs). The intrinsic complexity of these life-saving drugs is too challenging for synthesis by simple chemistry and requires the utilisation of living cells. Forcing cells to produce proteins that they do not naturally express is complex, and often requires a long period of trial and error cell manipulation, making the bio-manufacturing process time-consuming and very expensive and directly impacting on the delivery of transformative medicines to patients. With the recent remarkable development of powerful tools for editing mammalian genomes, new methods and automation for the synthesis of large numbers of DNA constructs, and the context provided by systems biology, the time is now right for using Synthetic Biology to establish a new paradigm for cost-effective manufacture of biologic drugs. In turn this will have a major impact on medicine and the health related industries, and make the biopharmaceutical value chain more cost-efficient.The scale of the economic opportunity associated with this project is enormous. The UK has one of the most dynamic and innovative healthcare industries in the world and has developed over 20% of the world's top 100 selling drugs. The medical technology sector in the UK consists of around 2,800 companies, employing 52,000 people and generating around £10.6bn of turnover annually. An increasing portion of all medicines, currently estimated at 20%, are biopharmaceuticals. The global biologics market was valued at an estimated $251.5 billion in 2018 and is predicted to reach $319 billion by 2021. The CHO cell is the most widely used industrial expression system, which generates ~70% of approved and marketed therapeutic recombinant proteins, including multiple monoclonal antibodies (mAbs), so any enhancement of production efficiency and quality has a huge economic impact. The vision of this prosperity partnership is to utilise state of the art investigational tools and synthetic biology approaches to both elucidate the intricacies of the CHO cell manufacturing platform and engineer it to be more predictive, effective, cost-efficient, and competitive for the production of biotherapeutics in the UK.