N.I. Vavilov Institute of General Genetics, Russian Academy of Science and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Expert Rev Vaccines. 2010 Aug;9(8):859-76. doi: 10.1586/erv.10.85.
In the molecular farming area, transient expression approaches for pharmaceutical proteins production, mainly recombinant monoclonal antibodies and vaccines, were developed almost two decades ago and, to date, these systems basically depend on Agrobacterium-mediated delivery and virus expression machinery. We survey here the current state-of-the-art of this research field. Several vectors have been designed on the basis of DNA- and RNA-based plant virus genomes and viral vectors are used both as single- and multicomponent expression systems in different combinations depending on the protein of interest. The obvious advantages of these systems are ease of manipulation, speed, low cost and high yield of proteins. In addition, Agrobacterium-mediated expression also allows the production in plants of complex proteins assembled from subunits. Currently, the transient expression methods are preferential over any other transgenic system for the exploitation of large and unrestricted numbers of plants in a contained environment. By designing optimal constructs and related means of delivery into plant cells, the overall technology plan considers scenarios that envisage high yield of bioproducts and ease in monitoring the whole spectrum of upstream production, before entering good manufacturing practice facilities. In this way, plant-derived bioproducts show promise of high competitiveness towards classical eukaryotic cell factory systems.
在分子农业领域,针对药物蛋白生产(主要是重组单克隆抗体和疫苗)的瞬时表达方法在大约二十年前就已开发出来,迄今为止,这些系统主要依赖于农杆菌介导的传递和病毒表达机制。我们在此调查了该研究领域的最新现状。已经基于 DNA 和基于 RNA 的植物病毒基因组设计了几种载体,并且根据感兴趣的蛋白质,将病毒载体单独或组合用作单组分和多组分表达系统。这些系统的明显优势在于易于操作、快速、低成本和高蛋白质产量。此外,农杆菌介导的表达还允许在植物中生产由亚基组装而成的复杂蛋白质。目前,与任何其他转基因系统相比,瞬时表达方法更倾向于在封闭环境中利用大量不受限制的植物。通过设计最佳的构建体和相关的细胞内传递手段,整体技术方案考虑了在进入良好生产规范设施之前,通过优化生物产品的高产量和易于监测整个上游生产范围的情景。通过这种方式,植物来源的生物产品有望在竞争激烈的经典真核细胞工厂系统中具有很高的竞争力。