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 all 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 its Receptor Binding Domain (RBD) 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.

中文翻译：

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在植物中试生产SARS-CoV-2相关蛋白：将室内农场快速用于生物制造设施的概念证明

当前的CoVid-19危机揭示了世界应对全球健康危机的能力的强项和弱项。当前生物制造能力的过度集中化造成了严重的弱点，这是一个令人关注的问题，即使这不是民族主义紧张局势的根源。从积极的方面来看，预印现象推动了科学数据和信息的空前共享，这大大增强了我们开发基于新技术的解决方案的能力。在这项工作中，我们探索在快速交换科学信息的背景下，植物生物工厂如何可以作为一种快速且易于适应的解决方案，用于本地制造生物试剂，尤其是重组抗体。为此，我们测试了我们的生产能力，在一个学术实验室的框架内，在数周的时间内，就得出了本氏烟草中针对SARS-CoV-2的六种不同重组单克隆抗体的毫克量。为了设计抗体，我们利用了其他数据来源，以及其他组织在预印本出版物中快速获得的DNA序列信息。单克隆抗体都被工程化为与人γFc融合并使用病毒载体瞬时表达的单链片段。同时，我们还在植物中生产了重组SARS-CoV-2 N蛋白及其受体结合域（RBD），并用它们来测试重组mAb的结合特异性。最后，对于其中的两种抗体，我们根据质外性液体的提取物分析了简单的按比例放大的生产方案。我们的结果表明，使用本氏烟草作为生产平台，在几乎没有基础设施要求的经过改建的温室中，克重抗SARS-CoV-2抗体可以在不到6周的时间内轻松生产。类似的程序可以很容易地用于产生诊断试剂，并且最终可以适应于快速的治疗反应。