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“Improving human health around the globe is one of the more tangible goals of modern biotechnology. [...] However, the availability of these new medicines for use by all those who need them, unfortunately, greatly depends on economic considerations, such as the cost of their development and production. Therefore, a major challenge of biotechnology is to reduce clinical innovations to economically viable practice”. (Mor and Mason, 2004)

The OVERARCHING THEME of our research is protein engineering with an emphasis on the use of plants as novel expression systems and focuses on applying this research in the area of advancing human health in this country and around the world.

At present, our research FOCUSES on finding solutions to two seemingly disparate medical problems. One project aims to create novel countermeasures against poisoning by organophosphorous chemical warfare (and pesticide) nerve agents. The other project’s goal is to create a preventative mucosal vaccine against HIV-1. On a closer consideration, however, the common threads of the two complementary efforts become apparent. Both present two of the major threats to our increasingly interconnected and interdependent world: that posed by chemical (and biological) terrorism and that posed by infectious diseases of pandemic proportions, such as HIV/AIDS. In both cases protein-based pharmaceuticals bear the promise of efficacious prophylaxis and therapy, and in both cases an inexpensive scalable production system is required.

The FUNDAMENTAL QUESTION our research group tackles is how the cellular machinery of plants and targeted foreign genes can be mutually adapted to allow the synthesis and accumulation of complex foreign protein products in a form that will maintain their desired biological functions. The protein products have to be expressed in sufficient quantities to allow for in-vivo testing and future economically-viable production. Progress in this arena requires pushing the discovery envelope in several parallel fronts: (a) identification of appropriate protein targets for which other production systems do not exist or have significant limitations (Matoba et al., 2004; Mor et al., 2001); (b) continuous development of robust, fast, and agronomically and environmentally sound plant-expression systems (Mor et al., 2003); (c) study of plant molecular processes, especially post-translational modifications, to enable their manipulation (Fletcher et al., 2004; Muralidharan et al., 2005, Fletcher et al, under revision and Geyer et al, in preparation); (d) pre-clinical and clinical testing of the plant-produced protein pharmaceuticals for their safety and efficacy (Geyer et al., 2005, Evron and Geyer et al, in preparation; Matoba et al., 2006; Matoba et al., 2004); and finally (e) to use insight gained through all the previous tiers for the development of the “next generation” of protein pharmaceuticals (Matoba et al, in preparation).

Fletcher, S.P., Geyer, B.C., Smith, A., Evron, T., Joshi, L., Soreq, H., and Mor, T.S. (2004). Tissue distribution of cholinesterases and anticholinesterases in native and transgenic tomato plants. Plant Mol Biol 55, 33-43.
Geyer, B.C., Muralidharan, M., Cherni, I., Doran, J., Fletcher, S.P., Evron, T., Soreq, H., and Mor, T.S. (2005). Purification of Transgenic Plant-Derived Recombinant Human Acetylcholinesterase-R. Chem Biol Interact 157-158, 331-334.
Matoba, N., Geyer, B.C., Kilbourne, J., Alfsen, A., Bomsel, M., and Mor, T.S. (2006). Humoral immune responses by prime-boost heterologous route immunizations with CTB-MPR(649-684), a mucosal subunit HIV/AIDS vaccine candidate. Vaccine 24, 5047-5055.
Matoba, N., Magerus, A., Geyer, B.C., Zhang, Y., Muralidharan, M., Alfsen, A., Arntzen, C.J., Bomsel, M., and Mor, T.S. (2004). A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs. Proc Natl Acad Sci U S A 101, 13584-13589.
Mor, T.S., and Mason, H.S. (2004). Transgenic plants as a source for subunit vaccines. In Handbook of Plant Biotechnology (Christou, P. and Klee, H., eds) West Sussex: John Wiley & Sons, Ltd., pp. 768-780.
Mor, T.S., Moon, Y.-S., Palmer, K.E., and Mason, H.S. (2003). Geminivirus vectors for high-level expression of foreign proteins in plant cells. Biotechnol Bioeng 81, 430-437.
Mor, T.S., Sternfeld, M., Soreq, H., Arntzen, C.J., and Mason, H.S. (2001). Expression of recombinant human acetylcholinesterase in transgenic tomato plants. Biotechnol. Bioeng. 75, 259–266.
Muralidharan, M., Soreq, H., and Mor, T.S. (2005). Characterizing pea acetylcholinesterase. Chemico-Biological Interactions 157-158, 406-407.