Elementary plant Biochemistry and Biotechnology (2+1)

Plants as bioreactors

 
• Plants are a useful alternative to animals for recombinant-protein production because they are inexpensive to grow and scale-up from laboratory testing to commercial production is easy. Therefore, there is much interest in using plants as production systems for the synthesis of recombinant proteins and other speciality chemicals. There is some concern that therapeutic molecules produced in animal expression systems could be contaminated with small quantities of endogenous viruses or prions, a risk factor that is absent from plants. Furthermore, plants carry out very similar post-translational modification reactions to animal cells, with only minor differences in glycosylation patterns. Thus plants are quite suitable for the production of recombinant human proteins for therapeutic use. A selection of therapeutic proteins that have been expressed in plants is listed in Table.


• The first such report was the expression of human growth hormone, as a fusion with the Agrobacterium Nopaline synthase enzyme, in transgenic tobacco and sunflower. Tobacco has been the most frequently used host for recombinant-protein expression although edible crops, such as rice, are now becoming popular, since recombinant proteins produced in such crops could in principle be administered orally without purification. The expression of human antibodies in plants has particular relevance in this context, because the consumption of plant material containing recombinant antibodies could provide passive immunity (i.e. immunity brought about without stimulating the host immune system).


• Antibody production in plants was first demonstrated by Hiatt and During team, who expressed full-size immunoglobulins in tobacco leaves. Since then, many different types of antibody have been expressed in plants, predominantly tobacco, including full-size immunoglobulins, Fab fragments and single-chain Fv fragments (scFvs). For example, a fully humanized antibody against herpes simplex virus-2 (HSV-2) has been expressed in soybean. Even secretory IgA (sIgA) antibodies, which have four separate polypeptide components, have been successfully expressed in plants. This experiment involved the generation of four separate transgenic tobacco lines, each expressing a single component, and the sequential crossing of these lines to generate plants in which all four transgenes were stacked. Plants producing recombinant sIgA against the oral pathogen Streptococcus mutans have been generated, and these plant-derived antibodies (‘plantibodies’) have recently been commercially produced as the drug CaroRxTM, marketed by Planet Biotechnology Inc.
Table. Selective examples of recombinant human therapeutic proteins expressed in plants