Development of a chloroplast-directed production platform for therapeutic proteins

开发治疗性蛋白质叶绿体定向生产平台

• 批准号: 544086-2019
• 负责人: Smith, Matthew
• 金额: $ 1.82万
• 依托单位: Wilfrid Laurier University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=680471
• 关键词: Development; chloroplast; directed; production; platform

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.

重组蛋白在植物中的瞬时表达，如使用农杆菌菌株渗入烟草和相关物种的叶中所实现的，正越来越多地用作治疗性蛋白如单克隆抗体、酶和疫苗的生产平台。该系统的好处包括降低药品成本，快速向市场交付新产品，以及为癌症，关节炎和其他自身免疫性疾病等疾病提供安全有效药物的能力。PlantForm Corporation是一家加拿大生物技术公司，开发了这样一种系统，用于生产Humira®和Herceptin®等治疗药物的生物仿制药，以及针对HIV和埃博拉病毒等病原体的创新产品。PlantForm的技术被称为vivoXPRESS®（www.plantformcorp.com），其基础是使用常见的植物病原体（根癌土壤杆菌）将编码产品的基因递送到本氏烟草植物的细胞中，使得植物成为制造产品的工厂。并不是所有进入该公司管道的候选产品都取得了成功：有些产品表达量较低，偶尔也会对正常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性蛋白质都是分泌性糖蛋白，它们通过内质网（ER）/高尔基体进行加工，并从具有人型糖基化的质外体中回收。拟议的项目将研究表达和靶向叶绿体的一些模型治疗蛋白质，这些蛋白质已被证明难以使用该公司目前的技术表达。PlantForm的科学家们有兴趣评估叶绿体靶向作为目前将蛋白质引导到质外体空间的方法的替代方案。