Development of a chloroplast-directed production platform for therapeutic proteins

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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.