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Plant viral vectors for delivery by Agrobacterium

机译:农杆菌传递的植物病毒载体

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Plant viral vectors delivered by Agrobacterium are the basis of several manufacturing processes that are currently in use for producing a wide range of proteins for multiple applications, including vaccine antigens, antibodies, protein nanoparticles such as virus-like particles (VLPs), and other protein and protein-RNA scaffolds. Viral vectors delivered by agrobacterial T-DNA transfer (magnifection) have also become important tools in research. In recent years, essential advances have been made both in the development of second-generation vectors designed using the 'deconstructed virus' approach, as well as in the development of upstream manufacturing processes that are robust and fully scalable. The strategy relies on Agrobacterium as a vector to deliver DNA copies of one or more viral RNA/DNA replicons; the bacteria are delivered into leaves by vacuum infiltration, and the viral machinery takes over from the point of T-DNA transfer to the plant cell nucleus, driving massive RNA and protein production and, if required, cell-to-cell spread of the replicons. Among the most often used viral backbones are those of the RNA viruses Tobacco mosaic virus (TMV), Potato virus X (PVX) and Cowpea mosaic virus (CPMV), and the DNA geminivirus Bean yellow dwarf virus. Prototypes of industrial processes that provide for high yield, rapid scale up and fast manufacturing cycles have been designed, and several GMP-compliant and GMP-certified manufacturing facilities are in place. These efforts have been successful as evidenced by the fact that several antibodies and vaccine antigens produced by magnifection are currently in clinical development.
机译:农杆菌传递的植物病毒载体是几种生产工艺的基础,目前正在生产各种用途广泛的蛋白质,包括疫苗抗原,抗体,蛋白质纳米颗粒(如病毒样颗粒(VLP))和其他蛋白质和蛋白质RNA支架。通过农杆菌T-DNA转移(magnfection)递送的病毒载体也已成为研究的重要工具。近年来,在使用“解构病毒”方法设计的第二代载体的开发以及强大且完全可扩展的上游制造工艺的开发方面都取得了重要进展。该策略以农杆菌为载体,可递送一种或多种病毒RNA / DNA复制子的DNA拷贝。细菌通过真空渗透进入叶片,病毒机制从T-DNA转移到植物细胞核,从而驱动大量RNA和蛋白质产生,并在必要时推动复制子在细胞间扩散。最常用的病毒主链是RNA病毒的主链,其中包括烟草花叶病毒(TMV),马铃薯X病毒(PVX)和Cow豆花叶病毒(CPMV),以及DNA双子叶病毒Bean黄矮病毒。已经设计出可提供高产量,快速扩大规模和快速制造周期的工业流程原型,并且已经建立了一些符合GMP要求和GMP认证的制造设施。这些努力已获得成功,这是由magnafection生产的几种抗体和疫苗抗原目前正在临床开发这一事实所证明的。

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