Battelle Develops Transgenic Plant Protein Production Platform

If your company is looking for plant-based protein sources, look into a new transgenic tobacco from Battelle's Pacific Northwest Laboratory. Battelle scientists have developed a new transgenic plant protein production platform, dubbed tP4, and are looking for industrial commercialization partners. They claim that tP4 is a safer and much less expensive route to high-value proteins useful in the manufacture of pharmaceutical, agricultural, chemical, food, diagnostic, and consumer products.

Using tP4, plants are rapidly, genetically transformed, resulting in "plants as bioreactors" that synthesize protein products and crop plants phenotypes that possess unique, beneficial properties. The tP4 system relies on established molecular biology methods for efficient expression of specific proteins.

Examples of specific proteins already produced using tP4 include cellulases (applications in textile, chemical process, and food processing industries) and human growth factors (potential wound care therapeutic).

The tP4 system has the following novel capabilities:

• Product quality, safety, and stability. Consistent product quality is essential for all protein product applications. Problems associated with traditional recombinant techniques (microbial fermentation and mammalian cell culture), including improper folding, pyrogenicity, and pathogen transmission, may be circumvented since transgenic plants produce properly processed, biologically active proteins with greatly reduced pathogen transmission risk. Stability of production is also enhanced as transgenic plant seeds may be stored indefinitely and subsequently planted for optimum product delivery.
• Whole plant and suspension cell transformation. Both of these systems possess distinctive advantages for production, cost, and regulatory concerns over the current methods. Whole plant production strategies afford ease in scale-up to meet varying product demands while dramatically reducing capital equipment costs. Cell culture production strategies are directly portable to industries currently using fermentation equipment and where strict process validation is crucial for product approval. By possessing capabilities in both systems, the development time required to produce large quantities of single proteins is greatly reduced through 1) rapid transformation and transformant screening (successful transformation and screening activities may require as little as three months), 2) efficient proliferation of plant material, and 3) ease and flexibility in production system scale-up.

Targeted expression of proteins in the non-crop portion of a plant

• Ability to target specific plant portions for overexpression. Targeted expression of foreign proteins in designated plant organs allows for the formulation of novel harvesting and separation strategies. Depending on production/formulation constraints of the foreign protein to be over-expressed, synthesis may be limited to plant roots, leaves, or fruit. Additionally, at the cellular level, products may be targeted to specific organelles, affording 1) a protective environment to sequester enzymes that may be deleterious to plants, 2) necessary protein folding and other post-translational modifications, and 3) simplified downstream separations.
• Applications-based product delivery. To maintain competitiveness, the product formulation must cost-effectively match its application. For example, an industrial enzyme preparation may require only a fraction of the purification/validation necessary for protein therapeutics and reagents. The tP4 system uses specific strategies to minimize cost in product delivery, while maintaining formulations that effectively deliver the necessary catalytic function.
• Design and scale-up of production systems. Past experience in large- and medium-scale cell culture fermentation and product separations allows Battelle scientists to develop both novel transgenic plants and the market-scale production systems needed for either whole plants or cell culture.

For More Information: Brian Hooker, staff scientist, Battelle Pacific Northwest Division, Battelle, P.O. Box 999, Richland, WA 99352. Tel: 509-375-4420. Email: brian.hooker@pnl.gov.