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生物制药的绿色工厂。

Green factories for biopharmaceuticals.

机构信息

Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.

出版信息

Curr Med Chem. 2013;20(8):1038-46.

PMID:23210788
Abstract

Plants and plant cells have been used to produce many diverse and valuable recombinant proteins, including subunit vaccines, antibodies and antibody fragments, hormones, blood products, cytokines and enzymes. Different plant species and platforms have been explored as production hosts, each with unique properties in terms of production timescales, environmental containment, scalability, downstream processing strategy and overall costs. Whole plants are suitable for the economical and safe production of recombinant proteins on a large scale, providing unique advantages for pharmaceutical proteins that are required in large amounts and normally too expensive for conventional manufacturing processes. Seed-based systems have additional advantages because they exploit the natural storage properties of seeds to facilitate batch processing and distribution. The stabilizing effect of seeds after harvest allows recombinant subunit vaccines and antibodies to be delivered via the mucosal route as they are better able to withstand the harsh microenvironment when protected by the plant matrix. Although the differences between plant and human N-glycans were initially thought to limit the therapeutic potential of plant-derived glycoproteins, several such products have now been tested in the clinic and in some cases the presence of plant glycans has been turned into an advantage because they improve the performance of the protein or confer unique characteristics. In this review we discuss recent case studies of recombinant pharmaceuticals produced in plants to demonstrate the versatility and unique advantages of molecular farming and the bottlenecks that remain to be addressed.

摘要

植物和植物细胞已被用于生产许多不同且有价值的重组蛋白,包括亚单位疫苗、抗体和抗体片段、激素、血液制品、细胞因子和酶。不同的植物物种和平台已被探索作为生产宿主,每个宿主在生产时间、环境控制、可扩展性、下游处理策略和总体成本方面都具有独特的特性。整个植物适合大规模经济且安全地生产重组蛋白,为需要大量且通常由于传统制造工艺而过于昂贵的药物蛋白提供了独特的优势。基于种子的系统具有额外的优势,因为它们利用种子的天然储存特性来促进批量处理和分配。收获后种子的稳定作用允许通过粘膜途径递送重组亚单位疫苗和抗体,因为它们在受到植物基质保护时能够更好地耐受恶劣的微环境。尽管最初认为植物和人类 N-聚糖之间的差异会限制植物来源糖蛋白的治疗潜力,但现在已经有几种此类产品在临床上进行了测试,在某些情况下,植物糖的存在已被转化为优势,因为它们提高了蛋白质的性能或赋予其独特的特性。在这篇综述中,我们讨论了在植物中生产的重组药物的最近案例研究,以展示分子农业的多功能性和独特优势,以及仍然需要解决的瓶颈问题。

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