A Novel Single Subunit RNA Polymerases for Commercial RNA Manufacturing

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The use of enzymes called RNA polymerases for the efficient production of mRNA is enormously important for the burgeoning field of cell-free protein production and use in an expanding range of biosensor applications, however, the largest market opportunity is in the RNA therapeutics and vaccines arena. mRNA holds the potential to revolutionise vaccination, protein replacement therapies, and the treatment of genetic diseases. The use of mRNA for the expression of therapeutic proteins holds the potential to treat or prevent a wide range of diseases including (1) restoration of the function of a single protein for rare monogenic diseases; (2) cell reprogramming and (3) immunotherapies where mRNA encoded transcripts provoke immune responses against targets such as tumour cells and (4) RNA vaccines, currently the largest market. Most traditional vaccines are made from proteins produced by infectious microbes, or from weakened forms of the microbes themselves. RNA vaccines however work by introducing an mRNA sequence encoding a disease specific antigen that gets translated into protein as soon as it gets into the cell cytoplasm. Once produced within the body, the antigen is recognised by the immune system, triggering recognition of the disease. RNA vaccines offer many advantages, including the ability to design a rapid response manufacturing platform. Their ease of production would allow distributed, localised manufacturing systems to meet the challenges of any emerging disease epidemic within a relatively short time and in the geography where it is needed. RNA based vaccines are also safer for the patient, as they are not produced using infectious elements. The global RNA drugs market is forecast to exceed $10 billion by 2024 (based on an analysis carried out using the GlobalData Plc database), highlighting the significant commercial potential of this emerging class of therapeutics. Currently T7 RNA polymerase is the gold standard for industrial mRNA production but there is great interest in improved alternative RNA polymerases. In our preliminary work we have identified a novel single subunit RNA polymerase and cognate synthetic promoters. In this project we aims to further characterise and further develop our novel RNA polymerase (and its mutant derivatives) in order to establish a strong patent position for licencing to industry. A new efficient RNAP could potentially be highly disruptive and would reduce the costs of RNA manufacturing and use in R and D bringing more affordable products to the mRNA vaccine market for the benefit of patients.