21EBTA: Engineering plant cell factories for the production of biomedicines and their ingredients. (Acronym; Celfacto)

由严重急性呼吸综合征冠状病毒（SARS-CoV-2）引起的COVID-19大流行是无法预测的，但科学发现在我们控制疾病状态的能力中发挥了重要作用。尽管疫苗的扩大已得到高度宣传，但支撑其发展的是多年来开发的广泛科学工具和资源。我们提出的项目将开发这些工具和资源，以确保生物学可以在未来提供更好的治疗和预防。这些方法将不仅限于COVID-19，还将适用于许多其他生物医学。该项目将使用基于植物的主机作为其生产平台，从本质上讲，这意味着该系统是可持续的，不会使用化石燃料衍生的前体和能源，从而提高了制造过程的环境证书。将使用新的植物育种技术（npbt），这意味着所使用的遗传操作更容易被消费者接受，程序将被控制，将使用瞬时表达，而稳定转化的材料将只使用来自性相容物种的基因。拟采用的植物品种为本拟烟。这种类型的烟草可以适应土壤细菌农杆菌的快速侵染，这有利于外源基因的瞬时表达。我们有价值的生产目标将是：(i)角鲨烯；这种分子是主要的佐剂，这意味着它可以刺激我们的免疫系统，有效接种所需的蛋白质（抗原）更少，它可以形成纳米结构，更好地维持功能性蛋白质结构。目前角鲨烯是从鲨鱼的鱼肝油中提取的，供不应求。（二）SARS-CoV-2中和抗体将在植物基平台中生产。这些抗体代表了一种治疗COVID的方法，超越了目前只有在患者没有病毒的情况下才有效的预防性疫苗接种方法。（三）将在该规划中生成SARS-CoV-2的病毒样颗粒（VLPs），这些是安全的结构，可提供更好的疫苗成分，因为它们更精确地代表或模拟病毒的结构，从而产生更好的免疫反应。产量和质量是影响生物医药采用和广泛使用植物制造的主要决定因素。我们的项目将通过产生几种蛋白酶活性降低和糖基化电位改变的品系来解决这些问题。通过这种方式，蛋白质产品的降解所造成的损失和变化将减少，从而提高竞争力。此外，通过去除植物衍生糖基化的多样化潜力，产品将在性质上更像人类。总的来说，这些产出具有重要的社会和经济效益，综合对话将用于向不同的利益攸关方提供信息。这些活动将包括在英国和国际上进行的焦点小组和讲习班。

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) was impossible to predict, but scientific discoveries have played a major role in our ability to manage the disease state. Although the vaccine scale-up has been highly publicised, underpinning their development is a wide range of scientific tools and resources developed over many years. Our proposed project will develop these tools and resources to ensure, biology can be used to deliver better treatments and preventions in the future. The approaches will not be limited to COVID-19 but will have applicability to many other biomedicines. The project will use a plant-based host as its production platform, by nature this means the system is sustainable and will not use fossil fuel derived precursors and energy, thus improving the environmental credentials of the manufacturing process. New Plant Breeding Techniques (NPBTs) will be used, which implies the genetic manipulations used are more acceptable to the consumer, the procedures will be contained, transient expression will be used, while stably transformed material will only use genes from sexually compatible species. The plant species to be used is Nicotiana benthamiana. This type of tobacco accommodates rapid infection by soil bacterium Agrobacterium, which facilitates the transient expression of heterologous genes. Our valuable production targets will be:(i) Squalene; this molecule is the leading adjuvant, which means in can stimulate our immune system, less protein (antigen) is required for effective vaccination and it can form nano-structures that better maintain functional protein structures. Presently squalene is extracted from sharks' liver oil and demand is outstripping supply.(ii) SARS-CoV-2 neutralising antibodies will be produced in the plant based platform. These antibodies represent a treatment for COVID which goes beyond the current preventative vaccination approach that will only work if patients do not have the virus. (iii) Virus Like Particles (VLPs) of SARS-CoV-2 will be generated in the programme, these are safe structures that offer better vaccine components, as they represent or mimic the structure of the virus more precisely, leading to better immunological responses. Production yield and quality are major determinants influencing the adoption and widespread use of plant-based manufacturing for biomedicines. Our project will address these aspects by generating several lines with reduced protease activity and altered glycosylation potential. In this way the losses and alterations by degradation of the protein products will be reduced improving competitiveness. In addition, by removing the diverse potential for plant derived glycosylation, the products will be more human-like in nature. Collectively these outputs have important societal and economic benefits and integrated dialogue will be used to inform diverse stake holders. These activities will include focus groups and workshops performed in the UK and internationally.