Development of a chloroplast-directed production platform for therapeutic proteins

重组蛋白在植物中的瞬时表达是通过农杆菌菌株渗透到烟草和相关物种的叶片中实现的，越来越多地被用作生产治疗性蛋白的平台，如单抗、酶和疫苗。这一系统的好处包括降低药物产品的成本，快速向市场交付新产品，以及能够为癌症、关节炎和其他自身免疫性疾病等疾病提供安全有效的药物。PlantForm Corporation是一家加拿大生物技术公司，该公司开发了这样一种系统，以生产生物相似版本的治疗药物，如Humira®和Herceptin®，以及针对艾滋病毒和埃博拉病毒等病原体的创新产品。PlantForm技术的基础是使用一种常见的植物病原体(根癌农杆菌)将编码该产品的基因输送到本氏烟草植物的细胞中，使该工厂成为生产该产品的工厂。并不是所有进入该公司流水线的候选产品都表现出成功：一些产品的表达水平很低，有时还会对正常的植物形态和生理产生多效性影响。PlantForm产品线中的大多数治疗蛋白是分泌的糖蛋白，通过内质网(ER)/高尔基体加工，并通过人类类型的糖基化从质外体中回收。拟议的项目将研究几种模型治疗性蛋白质的表达和靶向，这些蛋白质已被证明很难使用该公司目前的技术表达。PlantForm的科学家们感兴趣的是评估叶绿体靶标作为当前将蛋白质引导到质外体空间的替代方法。

Transient expression of recombinant protein in plants, as achieved using infiltration of Agrobacterium strains into the leaves of tobacco and related species, is increasingly being used as a production platform for therapeutic proteins such as monoclonal antibodies, enzymes, and vaccines. Benefits of this system include reduced cost of drug products, rapid delivery of new products to the market, and ability to provide safe and efficacious medicines for diseases such as cancers, arthritis and other autoimmune diseases. PlantForm Corporation is a Canadian biotechnology company that has developed such a system to produce biosimilar versions of therapeutics such as Humira® and Herceptin® as well as innovator products against pathogens such as HIV and Ebola virus. The basis of PlantForm's technology, known as vivoXPRESS® (www.plantformcorp.com), is to use a common plant pathogen (Agrobacterium tumefaciens) to deliver the genes encoding the product to cells of Nicotiana benthamiana plants such that the plant becomes a factory for manufacture of the product. Not all product candidates that enter the company's pipeline show success: some suffer low expression and, occasionally, some cause pleiotropic effects on normal plant morphology and physiology. Most of the therapeutic proteins in PlantForm's product pipeline are secreted glycoproteins which are processed through the endoplasmic reticulum (ER)/Golgi apparatus and are recovered from the apoplast with human-type glycosylation. The proposed project will investigate expression and targeting to the chloroplast of a few model therapeutic proteins that have proven difficult to express using the company's current technology. PlantForm scientists are interested in evaluating chloroplast targeting as an alternative to the current approach of directing proteins to the apoplastic space.