Automated and digitalised RNA process-in-a-box for rapid outbreak-response disease-agnostic RNA vaccine/therapeutic development and manufacturing at high-quality and low cost

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The ribonucleic acid (RNA) vaccine platform technology has been developed for over two decades and has been largely validated during the COVID-19 pandemic. Although this first iteration of RNA vaccines was clinically successful, there is still substantial room for improving the production process to increase production rates and volumes 10-fold, and to reduce manufacturing costs 6-7-fold, whilst maintaining consistently high product quality. The rate at which vaccines against Disease X can be developed and manufactured for large-scale human use is often limited by Chemistry, Manufacturing and Controls (CMC).To remove this CMC bottleneck and to unleash the disease-agnostic platform potential of the RNA technology we are taking a unique and innovative approach which combines the following two synergistic components: 1) design and construct a fully automated continuous RNA-foundry-in-a-box (RNAboxTM) that will allow the manufacturing of both R&D grade and GMP grade materials and 2) develop a bespoke design space based on the Quality by Digital Design (QbDD) framework that will allow the production of the different RNA sequences (translating into different products) using the same automated and continuous RNAbox.The QbDD-enabled RNAbox will provide RNA material for: 1) basic research to study molecular mechanisms, biochemical and cellular signalling pathways as well as disease mechanisms, 2) formulation science studies, 3) studies in animal models and 4) clinical trials. Moreover, it will also provide commercial-scale GMP manufacturing of regulatory-approved products. This will help with epidemic/pandemic preparedness as well as with the development and manufacturing of numerous vaccines against a wide range of diseases.The above will substantially enhance UK's position in RNA vaccine/therapeutic development and manufacturing. In addition, this automated manufacturing technology will not require substantial operator training and will provide high-quality and low-cost RNA material. It will also be suitable for vaccine manufacturing in low- to middle-income countries (LMICs), because of the low-cost (due to efficient raw material use) and lower-skilled manufacturing (due to automation) in lower-grade clean rooms (e.g. EU GMP Grade D, due to the hermetically sealed process). Customers will include vaccine manufacturers, biotechnology companies, pharmaceutical companies, contract (development) manufacturing organizations, research institutes, and academic groups. The global deployment of the QbDD-enabled RNAbox will establish a distributed vaccine and therapeutics manufacturing network which will lead to epidemic/pandemic preparedness and improved health through prevention and treatment of diseases.