Bioreactor enhances interleukin-12 production in genetically modified tobacco plants

Scientists from Worcester Polytechnic Institute's Life Sciences and Bioengineering Centre (WPI) and the Arkansas Bioscience Institute (ABI) in the US have published details of their work producing an important immune system protein in plants.

They report that hairy roots from genetically modified tobacco plants can be grown in a contained mist bioreactor system, yielding significant quantities of murine interleukin-12.

Interleukin-12 is a naturally occurring protein essential for the proper functioning of the human immune system. Having too much or too little interleukin-12 may play a role in the development of many diseases, including some cancers and auto-immune disorders such as Crohn's, psoriasis, and rheumatoid arthritis. In turn, modulating interleukin-12 levels could yield new therapies for those conditions.

Pamela Weathers, professor of biology and biotechnology at WPI and co-author of the report, said: "We are very encouraged by the results of this study. Interleukin-12 is a valuable protein and there just isn't enough available for biomedical research, let alone for therapeutic development. Our study shows that we can use plants to produce interleukin-12, and other therapeutic proteins, in a cost-effective controlled process."

In the current study, tobacco plants were modified in the lab of Carole Cramer, ABI's executive director and co-author of the paper. Cramer's team successfully inserted into tobacco plants a mouse gene that directs the production of interleukin-12. Hairy root cultures from those modified tobacco plants were then grown in a mist reactor developed in Weathers" laboratory. This reactor uses ultrasonic technology to spray a fine mist of water and nutrients on the root cultures, which are suspended in a plastic bag. The nutrient solution is collected at the bottom of the bag and recycled through the system. In this way, all of the materials are completely contained and isolated from the environment.

In the current study, Weathers compared the capabilities of the mist reactor with two other common methods for growing plant cultures the shake flask method and the airlift bioreactor. The results showed the mist reactor produced the highest concentration of interleukin-12.

Armed with these positive results, Cramer's team can now begin to study a human interleukin-12 gene's ability to direct the production of the human protein in tobacco plants.

A paper detailing the results of the study has been published online by the Biotechnology and Bioengineering journal.