Non-food interventions: Exploring plant biotechnology applications to therapeutic protein production.

The impressive advances of biotechnology in the last twenty years has greatly promoted the development of genetically modified (GM) crops worldwide. First generation GMOs, whose cultivation began in 1996, and second generation GMOs were usually create in order to improve the agronomic properties and the nutritional value of major food crops. To obtain this, a large number of transgenes have been successfully transferred into crops through biotechnology approaches (mainly by Agrobacterium tumefaciens and Gene gun based methodologies) to induce, among the others: herbicide resistance (such as LibertyLink and Roundup Ready rice), insect (such as MON810 maize) and disease resistance, salt and drought tolerance, yield increase and quality improvement (Lu and Yang, 2009). The agronomic improved varieties with enhanced tolerance to herbicides and insects have been successfully cultivated by millions of farmers worldwide being planted in 2011 on at least 160 million of hectares in 29 Countries (James, 2012). These transformations, sometimes involving the insertion of single genes (as for herbicide resistant varieties) and other times involving the reconstruction of entire and novel metabolic pathways in the host plants (as for golden rice; Ye et al., 2000), were mainly thought to reduce the environmental impact of agriculture or to improve quality, quantity and safety of food at affordable price to meet the feeding demand of the increasing world population. At the same time alternative use of GM plants have been explored and, in the recent years, several works carried out by independent research teams throughout the world successfully resulted in the development of transformed plants for various applications that can be globally referred as non-food intervention because these do not affect and have nothing to do with food. More in details in the last ten years an increased number of papers, among the other, reported on: i) development of genetically modified plants with enhanced biodegradation and phytoremediation capacity of organic xenobiotics, heavy metals, metalloids, soil and sediment pollution (Abhilash et al., 2009; Kotrba et al., 2009); ii) plant biotechnology solutions for bioenergy by means of increasing biomass production and yield, modifying lignin biosynthesis and pre-processing of biomass in planta by expressing cellulases and cellulosomes (Yuan et al., 2008); iii) use of plants as heterologous expression systems to obtain high levels of products with high commercial value, the application of biotechnology to this aim takes the name of molecular farming. Molecular farming, in principle, is a term referring to the use of GM crops (and not animal) to produce highly priced compounds, there are two types of molecular farming: Non-medical and Medical molecular farming. The first one refers to the production of industrial enzymes and polymers, one of the greatest development in this field is represented by the expression of biopolymers as bacterial polyhydroxyalkanoates for bio-plastic production (Tilbrook et al., 2011). Also the expression in plants of cellulosolytic enzymes for bioenergy production can be considered as a form of non-medical molecular farming. On the other hand, Medical molecular farming refers to the use of transgenic plants to produce biopharmaceuticals (Daniell et al., 2009; Tacket, 2009; Paul et al., 2011; Thomas et al., 2011). Medical molecular farming represents an unprecedented opportunity to manufacture cost affordable medicines and make them available at a global scale especially in underdeveloped countries (Paul et al., 2011)