Ways to economically recover recombinant proteins from transgenic tobacco

The economics of producing biopharmaceuticals from transgenic plants such as tobacco is still a roadblock to producing large quantities of urgently needed medicines, especially for people in underdeveloped nations.

Chenming (Mike) Zhang is testing a variety of ways to economically recover recombinant proteins from transgenic tobacco using different protein separation techniques.

Zhang, an assistant professor in the Department of Biological Systems Engineering (BSE) in the College of Engineering at Virginia Tech, is working with a team of three Ph.D. students to develop transgenic tobacco plants able to express recombinant proteins economically. Recombinant proteins are potential therapeutic agents for treating human and animal diseases and creating new vaccines. Plant-made vaccines are especially beneficial because plants are free of human diseases, reducing the cost to screen for viruses and bacterial toxins.

"Recombinant protein production from transgenic plants is challenging, not just from the molecular biology aspect of creating high expression plant lines, but also from the engineering aspect of recovering and purifying the proteins economically -- the importance of which cannot be overlooked," Zhang said.

Recombinant proteins are proteins expressed by a host other than their native hosts. For example, if the gene for human growth hormone is inserted into the genetic code of yeast (gene recombination), then the corresponding protein expressed in the yeast is called recombinant human growth hormone.

Zhang's research starts with introducing the genes of interest into tobacco plants and then developing economical processes for recovering and purifying the expressed proteins. Relaxin, one of the proteins his team is studying, could potentially benefit patients with asthma, hay fever, and even cardiovascular disease.

Because most recombinant proteins are for therapeutic uses, they need to be highly purified to be safe for human use. Thus, once a protein is expressed, whether by transgenic tobacco or bacteria, the protein first needs to be recovered into liquid solutions before purification.

"Because of the high purity required, the purification is rigorous and not surprisingly, very expensive. Therefore, development of more economical techniques for protein purification is always an engineering challenge in order to lower the cost of therapeutic proteins or biopharmaceuticals," Zhang said.

Zhang uses tobacco in his research because it is a non-food crop and is well suited as a "factory" for recombinant protein production. The leafy green tobacco plant is relatively easy to alter genetically and produces thousands of seeds and a great deal of biomass. As a non-food crop, genetically manipulated tobacco will not pose a safety threat to products consumed by humans. "Since tobacco is neither a food nor a feed-crop, transgenic tobacco will not enter our food chain," Zhang said.

The research is funded by the Jeffress Memorial Trust and the Tobacco Initiative.

Zhang is the director of both the Protein Separation Laboratory and the Unit Operations Laboratory at Virginia Tech. The Protein Separation Laboratory supports research in protein expression and purification process development from transgenic plants and other expression systems. The Unit Operations Laboratory supports a course by the same name taught by Zhang in biological systems engineering. He is also affiliated with the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences.

The College of Engineering Dean's Award for Outstanding Assistant Professor was presented to Zhang in 2004. His nomination was based on his extraordinary level of activities and accomplishments in curriculum development and teaching, development of a viable research program, and his cooperative efforts with colleagues at Virginia Tech and around the nation.

Before coming to Virginia Tech in 2001, Zhang was a research and development scientist for two years at Covance Biotechnology Services (now Diosynth RTP) in Cary, N. C.

Zhang received his bachelor's and master's degrees in metallurgical physical chemistry from the University of Science and Technology in Beijing, China, in 1986 and 1991, respectively. He received a second master's degree in physical and analytical chemistry in 1996 from Iowa State University as well as his Ph.D. in chemical engineering in 1999.