A Novel Single Subunit RNA Polymerases for Commercial RNA Manufacturing

使用称为RNA聚合酶的酶来有效生产mRNA对于新兴的无细胞蛋白质生产领域和在不断扩大的生物传感器应用范围中的使用是非常重要的，然而，最大的市场机会是在RNA治疗和疫苗竞技场中。mRNA有可能彻底改变疫苗接种，蛋白质替代疗法和遗传疾病的治疗。mRNA用于表达治疗性蛋白质具有治疗或预防多种疾病的潜力，包括（1）恢复用于罕见单基因疾病的单一蛋白质的功能;（2）细胞重编程和（3）免疫治疗，其中mRNA编码的转录物引起针对靶点如肿瘤细胞的免疫应答和（4）RNA疫苗，目前是最大的市场。大多数传统疫苗是由感染性微生物产生的蛋白质或微生物本身的弱化形式制成的。然而，RNA疫苗通过引入编码疾病特异性抗原的mRNA序列来起作用，该抗原一旦进入细胞质就被翻译成蛋白质。一旦在体内产生，抗原就会被免疫系统识别，从而引发疾病的识别。RNA疫苗具有许多优势，包括设计快速反应制造平台的能力。它们易于生产，将使分布式、本地化的制造系统能够在相对较短的时间内，在需要的地理位置上应对任何新出现的疾病流行的挑战。基于RNA的疫苗对患者也更安全，因为它们不使用感染性元件生产。到2024年，全球RNA药物市场预计将超过100亿美元（基于使用GlobalData Plc数据库进行的分析），凸显了这类新兴疗法的巨大商业潜力。目前，T7 RNA聚合酶是工业mRNA生产的金标准，但人们对改进的替代RNA聚合酶有很大的兴趣。在我们的初步工作中，我们已经确定了一种新的单亚基RNA聚合酶和同源合成启动子。在这个项目中，我们的目标是进一步研究和进一步开发我们的新型RNA聚合酶（及其突变衍生物），以便为工业许可建立强大的专利地位。一种新的高效RNAP可能具有高度破坏性，并将降低RNA制造和研发使用的成本，为mRNA疫苗市场带来更实惠的产品，造福患者。

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.