Molecular farming for new drugs and vaccines. Current perspectives on the production of pharmaceuticals in transgenic plants.

The first recombinant plant-derived pharmaceutical protein (PDP) was human serum albumin, initially produced in 1990 in transgenic tobacco and potato plants (Sijmons et al, 1990). Fifteen years on, the first technical proteins produced in transgenic plants are on the market, and proof of concept has been established for the production of many therapeutic proteins, including antibodies, blood products, cytokines, growth factors, hormones, recombinant enzymes and human and veterinary vaccines (Twyman et al, 2005). Furthermore, several PDP products for the treatment of human diseases are approaching commercialization (Table 1), including recombinant gastric lipase for the treatment of cystic fibrosis, and antibodies for the prevention of dental caries and the treatment of non-Hodgkin’s lymphoma (Ma et al, 2003). There are also several veterinary vaccines in the pipeline; Dow AgroSciences (Indianapolis, IN, USA) announced recently their intention to produce plant-based vaccines for the animal health industry. As molecular farming has come of age, there have been technological developments on many levels, including transformation methods, control of gene expression, protein targeting and accumulation, the use of different crops as production platforms (Twyman et al, 2003), and modifications to alter the structural and functional properties of the product. One of the most important driving factors has been yield improvement, as product yield has a significant impact on economic feasibility. Strategies to improve the recombinant protein yield in plants include the development of novel promoters, the improvement of protein stability and accumulation through the use of signals that target the protein to intracellular compartments, and the improvement of downstream processing technologies (Menkhaus et al, 2004). Attention is now shifting from basic research towards commercial exploitation, and molecular farming is reaching the stage at which it could challenge established production technologies that use bacteria, yeast and cultured mammalian cells. In this review, we highlight not only recent progress in molecular farming and its potential for commercial drug development and production, but also the regulatory control, biosafety and political impacts of the technology, and its related intellectual property (IP) issues.