Quality, yield and cost optimisations of in vitro transcription reactions for saRNA therapeutics

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The potential of nucleic acids as vaccines and therapeutics is only just being realised and the success of the Covid mRNA vaccines is due in part to the rate at which scale-up and manufacture was possible. VaxEquity is a biotechnology company seeking to develop novel, second-generation RNA based vaccines and therapeutics. Working in collaboration with the Centre for Process Innovation, this project will drive efficiencies in the manufacturing process for second generation RNA vaccines and therapeutics based on self-amplifying RNA and, specifically, for amulti-valent saRNA flu vaccine. The project will identify and define experimentally the Critical Quality Attributes (CQAs) i.e. the key properties for saRNA and the manufacturing variables that impact these CQAs for the process of RNA transcription (the creation of active RNA molecules from the more stable DNA template) in batch and fed batch processes. The process of capping the RNA to enhance stability, processing and translation will be evaluated in tandem with the manufacturing process and as a separate reaction after the primary saRNA synthesis is complete. Studies will be run at small, laboratory scale to identify the optimised conditions and the factors that critically impinge on these conditions. Optimised conditions will be tested to establish scalability for the subsequent manufacturing of a broad-acting saRNA influenza vaccine to proceed into preclinical and clinical development. Manufacturing nucleic acid-based medicines is expensive and through the optimisation of conditions for saRNA, which has the potential to reduce dose compared to mRNA by \>10-fold, significant savings from both raw materials and the size of future dose requirements can be achieved.The benefits of the project for the UK will be to identify, establish and protect an optimised process for saRNA manufacture in a partnership between the UK's leading independent technology innovation centre that has the right experts and practical capabilities for effective innovation of complex nucleic acid therapies and UK-based RNA vaccine and therapeutics biotechnology company VaxEquity.