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Improving molecular pharming with pathogen-derived effectors

利用病原体衍生效应物改善分子制药

基本信息

批准号：
2748514
负责人：
金额：
--
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Studentship
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=studentship-2748514
关键词：
Improving molecular pharming pathogen derived

项目摘要

The transient expression of proteins in plants offers unprecedented opportunities for the fast, safe, cheap and flexible production of vaccines, therapeutic antibodies and proteins for research purposes. Many proteins can be expressed in planta within days upon infiltrating leaves of the tobacco relative Nicotiana benthamiana (Nb) with Agrobacterium tumefaciens (agroinfiltration) carrying genes-of-interest on a transfer-DNA. Several companies use the agroinfiltration platform to produce vaccines (MedicaGo, Canada), antibodies (iBio, USA) and research proteins (LES, UK).However, although transiently expressed GFP can reach 50% of the total protein content, most recombinant proteins accumulate to a much lower level caused by e.g. immune responses induced by agroinfiltration, by mRNA degradation (silencing), and by bottlenecks in protein folding, secretion and post-translational modifications.The PROJECT AIM is to overcome these bottlenecks by identifying novel pathogen-derived effector proteins that boost recombinant protein expression levels. Plant pathogenic bacteria, fungi and oomycetes secrete hundreds of proteins that modify the host to suppress immunity and alter protein expression levels. Examples of these effectors are inhibitors of silencing, proteases, glycosidases and immune regulators. Silencing inhibitor P19, for instance, is an effector that is routinely used in agroinfiltration assays to boost recombinant protein expression through suppression of gene silencing.

蛋白质在植物中的瞬时表达为用于研究目的的疫苗、治疗性抗体和蛋白质的快速、安全、廉价和灵活的生产提供了前所未有的机会。在用在转移DNA上携带感兴趣基因的根癌农杆菌（Agrobacterium tumefaciens）浸润烟草相关的本氏烟草（Nicotiana benthamiana，Nb）的叶（农杆菌浸润）后的数天内，许多蛋白质可以在植物中表达。几家公司使用agroinfiltration平台生产疫苗（MedicaGo，加拿大），抗体然而，尽管瞬时表达的GFP可以达到总蛋白含量的50%，但是大多数重组蛋白积累到低得多的水平，这是由例如农杆菌浸润诱导的免疫应答、mRNA降解引起的。该项目的目的是通过鉴定新的病原体衍生的效应蛋白来克服这些瓶颈，所述效应蛋白提高重组蛋白的表达水平。植物病原细菌、真菌和卵菌分泌数百种蛋白质，这些蛋白质修饰宿主以抑制免疫并改变蛋白质表达水平。这些效应物的实例是沉默抑制剂、蛋白酶、糖苷酶和免疫调节剂。例如，沉默抑制剂P19是一种效应物，其常规用于农杆菌渗透测定以通过抑制基因沉默来促进重组蛋白表达。