This Small Business Innovation Research Phase I project aims to examine the feasibility of producing therapeutic proteins in transgenic plants with a biological safety switch that controls the pharmacological activity of the proteins. With the embedded switch, the therapeutics will be inactive during plant growth but could be recovered from the plant and reactivated in high yield during the purification process. The research objectives of this Phase I project are (1) to create a library of human therapeutic proteins modified with the company's switch technology ; (2) to design constructs for the expression of the modified proteins in Escherichia coli , and (3) to screen and select for optimized constructs. The best candidates will be cloned into Nicotiana tabacum in the follow on Phase II project. The transformed plants will be screened for varieties that show low protein activity under natural growing conditions and high expression with efficient recovery after the switch is triggered during purification. The commercial application of this project will be in the production of protein based biopharmaceuticals. These biopharmaceuticals are currently produced from mammalian cell culture or bacterial fermentation processes, and are characterized by high complexity, low reaction rates, low yields, and thus high production costs. Production in transgenic plant systems will have the advantages of decreased costs, increased scalability, and increased safety from human pathogens
