Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities.
Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities.
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DOI：
10.3389/fpls.2020.612781
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发表时间：
2020
影响因子：
5.6
通讯作者：
Orzáez D
中科院分区：
文献类型：
--
作者：
Diego-Martin B;González B;Vazquez-Vilar M;Selma S;Mateos-Fernández R;Gianoglio S;Fernández-Del-Carmen A;Orzáez D
当前的新冠肺炎危机正在暴露出世界应对全球卫生危机的能力的优势和弱点。目前的生物制造能力过度集中造成了一个严重的弱点，这是一个非常令人关切的问题，如果不是民族主义紧张局势的来源的话。从积极的一面来看，科学数据和信息在预印现象的推动下以前所未有的速度被分享，这大大加强了我们开发新的基于技术的解决方案的能力。在这项工作中，我们探索了如何在快速交换科学信息的背景下，植物生物工厂可以作为一种快速且易于适应的解决方案，用于本地生产生物反应剂，更具体地说是重组抗体。为此，我们在一个学术实验室的框架内，在几周内测试了我们在烟草中生产六种不同数量的针对SARS-CoV-2的不同重组单抗的能力。在抗体的设计中，除了其他数据来源外，我们还利用了其他小组在预印出版物中迅速提供的DNA序列信息。单抗被设计成单链片段，融合到人的伽马Fc上，并使用病毒载体瞬时表达。同时，我们还在PLANTA中获得了重组SARS-CoV-2N蛋白和Spike蛋白的受体结合域(RBD)，并用它们来检测重组mAbs的结合特异性。最后，对于其中两种抗体，我们检测了一种基于质外体提取液的简单放大生产方案。我们的结果表明，在改建的温室中，以本氏新月球藻为生产平台，在几乎不需要基础设施的情况下，6周多一点的时间就可以很容易地生产出克量的抗SARS-CoV-2抗体。类似的程序可以很容易地用于生产诊断试剂，最终可以用于快速治疗反应。
The current CoVid-19 crisis is revealing the strengths and the weaknesses of the world’s capacity to respond to a global health crisis. A critical weakness has resulted from the excessive centralization of the current biomanufacturing capacities, a matter of great concern, if not a source of nationalistic tensions. On the positive side, scientific data and information have been shared at an unprecedented speed fuelled by the preprint phenomena, and this has considerably strengthened our ability to develop new technology-based solutions. In this work, we explore how, in a context of rapid exchange of scientific information, plant biofactories can serve as a rapid and easily adaptable solution for local manufacturing of bioreagents, more specifically recombinant antibodies. For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. For the design of the antibodies, we took advantage, among other data sources, of the DNA sequence information made rapidly available by other groups in preprint publications. mAbs were engineered as single-chain fragments fused to a human gamma Fc and transiently expressed using a viral vector. In parallel, we also produced the recombinant SARS-CoV-2 N protein and the receptor binding domain (RBD) of the Spike protein in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies, we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Our results indicate that gram amounts of anti-SARS-CoV-2 antibodies could be easily produced in little more than 6 weeks in repurposed greenhouses with little infrastructure requirements using N. benthamiana as production platform. Similar procedures could be easily deployed to produce diagnostic reagents and, eventually, could be adapted for rapid therapeutic responses.
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影响因子：
13.8
作者：
Sainsbury, Frank;Thuenemann, Eva C.;Lomonossoff, George P.
通讯作者：
Lomonossoff, George P.
DOI：
10.1073/pnas.0606631103
发表时间：
2006-10-03
影响因子：
11.1
作者：
Giritch, Anatoli;Marillonnet, Sylvestre;Gleba, Yuri
通讯作者：
Gleba, Yuri
影响因子：
1.6
作者：
Diamos, Andrew G.;Mason, Hugh S.
通讯作者：
Mason, Hugh S.
影响因子：
4.1
作者：
Fernandez-del-Carmen, Asun;Juarez, Paloma;Orzaez, Diego
通讯作者：
Orzaez, Diego
影响因子：
7.4
作者：
Sarrion-Perdigones, Alejandro;Vazquez-Vilar, Marta;Orzaez, Diego
通讯作者：
Orzaez, Diego