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

21EBTA：工程植物细胞工厂，用于生产生物药品及其成分。

• 批准号: BB/W013932/1
• 负责人: Paul Fraser
• 金额: $ 152.9万
• 依托单位: Royal Holloway University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW013932%2F1
• 关键词: 21EBTA; Engineering; plant; cell; factories

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.

由严重急性呼吸道综合征冠状病毒（SARS-CoV-2）引起的COVID-19大流行无法预测，但科学发现在我们管理疾病状态的能力中发挥了重要作用。虽然疫苗的规模扩大已被高度宣传，但其发展的基础是多年来开发的广泛的科学工具和资源。我们提议的项目将开发这些工具和资源，以确保生物学在未来可以用于提供更好的治疗和预防。这些方法将不仅限于COVID-19，而且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认证。将使用新的植物育种技术（NPBTs），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仅使用来自性相容物种的基因。使用的植物物种是本氏烟草（Nicotiana benthamiana）。这种类型的烟草适应土壤细菌农杆菌的快速感染，这有助于异源基因的瞬时表达。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，有效接种疫苗所需的蛋白质（抗原）较少，并且它可以形成更好地保持功能蛋白质结构的纳米结构。目前，角鲨烯是从鲨鱼肝油中提取的，供不应求。(ii)SARS-CoV-2中和抗体将在基于植物的平台上生产。这些抗体代表了一种治疗COVID的方法，它超越了目前的预防性疫苗接种方法，这种方法只有在患者没有病毒的情况下才有效。(iii)SARS-CoV-2的病毒样颗粒（VLP）将在该计划中产生，这些是提供更好疫苗成分的安全结构，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。产量和质量是影响采用和广泛使用生物医药植物制造的主要决定因素。我们的项目将通过产生几个蛋白酶活性降低和糖基化潜力改变的品系来解决这些问题。通过这种方式，蛋白质产品降解造成的损失和改变将减少，从而提高竞争力。此外，通过消除植物源性糖基化的多样性潜力，产品在本质上将更加类似于人类。这些产出合在一起具有重要的社会和经济效益，将利用综合对话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举办的重点小组和讲习班。

项目成果

The potential of Metabolomics in assessing global compositional changes resulting from the application of CRISPR/Cas9 technologies

代谢组学在评估 CRISPR/Cas9 技术应用引起的整体成分变化方面的潜力

• DOI: 10.21203/rs.3.rs-2287743/v1
• 发表时间: 2022
• 作者: Drapal M

A xanthophyll-derived apocarotenoid regulates carotenogenesis in tomato chromoplasts.

• DOI: 10.1016/j.plantsci.2022.111575
• 发表时间: 2022-12
• 期刊: Plant science : an international journal of experimental plant biology
• 作者: C. D’Ambrosio;Adriana Lucia Stigliani;J. Rambla;Sarah Frusciante;G. Diretto;Eugenia M. A. Enfissi;A. Granell;P. Fraser;G. Giorio

The chemotype core collection of genus Nicotiana.

• DOI: 10.1111/tpj.15745
• 发表时间: 2022-06
• 期刊: PLANT JOURNAL
• 影响因子: 7.2
• 作者: Drapal, Margit;Enfissi, Eugenia M. A.;Fraser, Paul D.
• 通讯作者: Fraser, Paul D.

Carotenoid composition and sequestration in cassava ( Manihot esculentum Crantz) roots

木薯 (Manihot esculentum Crantz) 根中的类胡萝卜素组成和封存

• DOI: 10.1101/2023.12.19.572370
• 发表时间: 2023
• 作者: Drapal M