Protein pharmaceuticals

The high space-time yields are the result of a doubling time of only 30 min and its applicability for high cell-density cultures. However, it is hardly possible to excrete overexpressed proteins into cultivation media. In addition, accumulation of pyrogenic lipopoly-saccharides in its outer membrane (a distinctive feature of Gram-negative bacteria) make additional purification steps necessary if pharmaceutical proteins are produced by E. coli [29]. 

At the moment, most of these more exotic bacteria are mainly used in expression for fundamental studies. Considering the speed of developments in biotechnology, their application for industrial or pharmaceutical protein production might become even more important very soon. 

Stoger, E., Ma, J.K., Fischer, R. and Christou, P. (2005) Sowing the seeds of success pharmaceutical proteins from plants. Current Opinion in Biotechnology, 16 (2), 167-173. 

ABBOTT Bioresearch Center. ChemoCentryx. Hyseq Pharmaceuticals. Protein Design Labs. 

Fontana A, Spolaore B, Mero A, Veronese FM (2008) Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase. Adv Dmg Deliv Rev... 

As discussed above, wheat has been used only rarely for molecular farming. Thus far, the only example of a pharmaceutical protein produced in wheat is a single chain Fv antibody, which was expressed using the Ubil promoter and achieved a maximum expression level of 1.5 pg g 1 dry weight [77]. Transgenic wheat producing Aspergillus phytase has also been reported [78]. 

In Canada the interim regulatory amendments governing field trials with plants with novel traits that produce industrial or pharmaceutical proteins were more conservative than those issued in the United States [16]. For example, the CFIA is recommending that major food or feed species, and crops pollinated by honeybees, are not to be used for PRP production. The use of non-food, fiber, small acreage or new crops is encouraged. They asked that proponents consider the potential for escape of the crop or the transgene into the environment when choosing a crop platform. 

Production of Pharmaceutical Proteins in Plants and Plant Cell Suspension Cultures... 

When sufficiently high levels of expression and protein accumulation are achieved, efficient downstream processing protocols must be developed to insure product quality and the economic feasibility of production. As the demand for safe, recombinant pharmaceutical proteins continues to expand, the market potential of plant-produced recombinant proteins is considerable. Molecular farming can produce recombinant proteins at a lower cost than traditional expression systems based on microbial or animal cell culture, and without the risk of contamination with human pathogens. 

Possible contamination by chemical or biological substances is one of the most important concerns when producing pharmaceutical proteins. Plant cell cultures ensure the production of the desired protein in a controlled, sterile and sealed environment and can be adapted to cGMP conditions. Therefore, the risk of contamination is minimized and the production conditions can be modified more easily in a contained reactor than in the field. Another advantage is the ability to freeze plant suspension cells in liquid nitrogen [66, 67] so that master and working cell banks can be established, a prerequisite for cGMP procedures [68]. 

Tab. 7.2 Pharmaceutical proteins produced in plant suspension cultures... 

The production of pharmaceutical proteins in plants has clear advantages over traditional systems in terms of cost-efficiency and product safety, since there is no risk of contamination with human pathogens. Furthermore plants are much less likely than mammalian cells to be affected by the expression of certain human proteins, such as growth factors and cell cycle inhibitors [29]. Therefore, plants provide a strategic complement to existing microbial and animal production systems. 

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