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有限公司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，开发用于生产重组蛋白的下一代酵母，如生物制药。使用基因多样化的天然面包师酵母，为大规模工业生产过程而设计，我们培育了多达10亿的后代，并选择了适合产品和工艺选择的细胞。30多年来，贝克酵母一直被安全地用于胰岛素和疫苗等生物制剂的批量生产，与哺乳动物系统相比，它相对便宜。该项目旨在解决英国血清学检测中对SARS-CoV-2病毒抗原的迫切需求，用于识别对COVID-19具有免疫力的个体。Phenotypeca将生产用于制造特定抗原的酵母菌株，供牛津大学詹纳研究所（Jenner Institute）评估，并与英国建立合作伙伴关系，为血清学检测生产商提供这些抗原。SARS-CoV-2病毒粒子的某些部分与其他冠状病毒具有很强的同源性，这使得制作既具有特异性（无假阳性，有可能传播COVID-19）又具有敏感性（无假阴性，阻止有免疫力的人恢复正常活动）的测试具有挑战性。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年冠状病毒爆发后从酵母中成功制备高质量抗原的先前工作的指导下进行的。我们的目标是开发能够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.