The development of yeast strains to produce SARS-CoV-2 antigens for serological assays enabling the detection of COVID-19 cases in the UK population

Phenotypeca Ltd是一家位于诺丁汉大学合成生物学研究中心的生物技术公司，致力于开发用于生产重组蛋白质（如生物制药）的下一代酵母。我们使用基因多样的天然面包酵母，为大规模工业生产工艺设计，繁殖多达10亿个后代，并选择最适合产品和工艺的细胞。面包酵母已经安全地用于生物制剂的批量生产超过30年，如胰岛素和疫苗，并且与哺乳动物系统相比相对便宜。该项目旨在解决英国生产血清学检测对SARS-CoV-2病毒抗原的迫切需求，用于识别对COVID-19免疫的个体。Phenotypeca将生产用于生产特定抗原的酵母菌株，供牛津大学詹纳研究所评估，并与英国建立合作伙伴关系，将其供应给血清学检测生产商。SARS-CoV-2病毒体的部分与其他冠状病毒具有很强的同源性，因此生产既具有特异性又具有特异性的检测方法具有挑战性（无假阳性，有COVID-19传播的风险）和敏感（无假阴性，阻止具有免疫力的人恢复正常活动）。为了实现这一目标，我们从病毒颗粒结构蛋白的独特部分设计了多种抗原，包括已知与人类ACE2受体结合的暴露区域，这是在2003年冠状病毒爆发后成功从酵母中制备高质量抗原的先前工作的指导下进行的。我们的目标是开发用于分泌这些抗原的酵母菌株，以简化纯化和生产。

Phenotypeca Ltd is a biotechnology company based in the University of Nottingham's Synthetic Biology Research Centre developing next-generation yeast for the manufacture of recombinant proteins, such as biopharmaceuticals.Using a genetically diverse collection of natural baker's yeast engineered for large-scale industrial processes we breed up to a billion progeny and select cells optimised for the product and process of choice. Baker's yeast has been safely used for over 30-years for the bulk manufacture of biologics, such as insulin and vaccines, and is relatively inexpensive compared to mammalian systems.This project aims to address an urgent unmet need for SARS-CoV-2 viral antigens for the UK's production of serological assays, used to identify individuals with immunity to COVID-19\. Phenotypeca will produce yeast strains for the manufacture of specific antigens for evaluation by Oxford University's Jenner Institute, and build UK partnerships for their supply to serological assay producers.Parts of the SARS-CoV-2 virion have strong homology to other coronaviruses, making it challenging to produce tests that are both specific (no false positives, risking COVID-19 spreading) and sensitive (no false negatives, preventing people with immunity from returning to normal activities). To achieve this, we have designed multiple antigens from unique parts of the virus particle's structural proteins, including an exposed region known to bind the human ACE2 receptor, which has been guided by previous work that successfully made high-quality antigens from yeast after the 2003 coronavirus outbreak. We aim to develop yeast strains for the secretion of these antigens to simplify purification and manufacture.