Diego-Martin Borja, González Beatriz, Vazquez-Vilar Marta, Selma Sara, Mateos-Fernández Rubén, Gianoglio Silvia, Fernández-Del-Carmen Asun, Orzáez Diego
Instituto de Biología Molecular y Celular de Plantas (IBMCP), Consejo Superior de Investigaciones Científicas (CSIC) - Universidad Politécnica de Valencia (UPV), Valencia, Spain.
Front Plant Sci. 2020 Dec 23;11:612781. doi: 10.3389/fpls.2020.612781. eCollection 2020.
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 . 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 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 as production platform. Similar procedures could be easily deployed to produce diagnostic reagents and, eventually, could be adapted for rapid therapeutic responses.
当前的新冠疫情危机正揭示出全球应对全球卫生危机能力的优势与不足。一个关键弱点源于当前生物制造能力的过度集中，这即便不是引发民族主义紧张局势的根源，也是一个令人高度担忧的问题。从积极方面来看，在预印本现象的推动下，科学数据和信息以前所未有的速度得到了共享，这极大地增强了我们开发基于新技术解决方案的能力。在这项工作中，我们探讨了在科学信息快速交流的背景下，植物生物工厂如何能够作为一种快速且易于适应的解决方案，用于生物试剂的本地制造，更具体地说是重组抗体的制造。为此，我们在一个学术实验室的框架内，在短短几周内测试了我们生产毫克量的六种不同抗SARS-CoV-2重组单克隆抗体的能力。对于抗体的设计，我们除了利用其他数据源外，还利用了其他团队在预印本出版物中迅速提供的DNA序列信息。单克隆抗体被设计为与人γFc融合的单链片段，并使用病毒载体进行瞬时表达。与此同时，我们还生产了重组SARS-CoV-2 N蛋白和刺突蛋白的受体结合域（RBD），并用于测试重组单克隆抗体的结合特异性。最后，对于其中两种抗体，我们测定了一种基于质外体流体提取的简单放大生产方案。我们的结果表明，使用作为生产平台，在基础设施需求很少的改造温室中，仅需6周多一点的时间就能轻松生产克量的抗SARS-CoV-2抗体。类似的程序可以很容易地用于生产诊断试剂，最终还可以适用于快速的治疗反应。
