A Novel Single Subunit RNA Polymerases for Commercial RNA Manufacturing

用于商业 RNA 生产的新型单亚基 RNA 聚合酶

• 批准号: BB/T017236/1
• 负责人: Susan Rosser
• 金额: $ 25.78万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT017236%2F1
• 关键词: Novel; Single; Subunit; RNA; Polymerases

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.

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以及在不断扩大的生物传感器应用中的使用非常重要，然而，最大的市场机会是在 RNA 治疗和疫苗领域。 mRNA 具有彻底改变疫苗接种、蛋白质替代疗法和遗传疾病治疗的潜力。使用 mRNA 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）恢复单个蛋白质的功能，以治疗罕见的单基因疾病； (2) 细胞重编程和 (3) 免疫疗法，其中 mRNA 编码的转录本激发针对肿瘤细胞等靶标的免疫反应，以及 (4) RNA 疫苗，目前是最大的市场。大多数传统疫苗是由传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 疫苗的工作原理是引入编码疾病特异性抗原的 mRNA 序列，该抗原一旦进入细胞质就会被翻译成蛋白质。一旦在体内产生，抗原就会被免疫系统识别，从而引发对疾病的识别。 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，使得分布式、本地化的制造系统能够在相对较短的时间内并在需要的地理位置应对任何新出现的疾病流行的挑战。基于 RNA 的疫苗对患者来说也更安全，因为它们不是使用传染性元素生产的。预计到 2024 年，全球 RNA 药物市场将超过 100 亿美元（基于使用 GlobalData Plc 数据库进行的分析），凸显了这一新兴疗法的巨大商业潜力。目前，T7 RNA 聚合酶是工业 mRNA 生产的黄金标准，但人们对改进的替代 RNA 聚合酶非常感兴趣。在我们的初步工作中，我们已经鉴定了一种新型单亚基 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表征和进一步开发我们的新型 RNA 聚合酶（及其突变衍生物），以便为行业许可建立强大的专利地位。一种新的高效 RNAP 可能具有高度颠覆性，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。