Molecular Farming in Plants

The large-scale production of recombinant proteins in plants is known as molecular farming (Fischer and Emans, 2000). It is now widely recognised that plants provide a unique combination of advantages over more traditional expression systems, such as bacteria, yeast, mammalian cell lines and transgenic animals (Giddings et al., 2000; Giddings, 2001; Hood, 2002; Schillberg et al., 2002). From a commercial perspective, the major benefit is the anticipated cost savings since there are no requirements for expensive equipment or skilled labour.

Transgenic plants can be maintained, harvested and processed using normal agricultural practices and existing infrastructure. Other advantages include the ease of scale-up, the absence of human/animal pathogens and undesirable DNA sequences (oncogenes, endogenous retroviruses, etc.) and the structural and functional similarities between plant-derived recombinant proteins and their native counterparts.

Plants have therefore been used to produce a wide range of products, including therapeutic human proteins, recombinant antibodies, subunit vaccines, nutraceuticals, animal feed additives, biopolymers, molecular biology reagents and industrial enzymes. These range from simple polypeptides to complex proteins with multiple subunits, disulphide bonds and glycan chains. Some plant-derived recombinant proteins are now reaching commercial status, and a comprehensive list has been assembled in several recent reviews (Fischer and Emans, 2000; Daniell et al., 2001b; Giddings et al., 2000; Giddings, 2001; Hood, 2002; Stoger et al., 2002a).

Early demonstrations of recombinant protein production in plants involved model species and varieties due to the availability of well-established transformation protocols and suitable expression constructs. Model tobacco varieties have been used for the expression of most foreign proteins to date, beginning with the first human protein to be expressed in plants—growth hormone—which was produced as a fusion protein with the Agrobacterium nopaline synthase enzyme (Barta et al., 1986). However, for large-scale production it is necessary to transfer the technology from model varieties to commercial cultivars. Typically, the expression of a given protein (or protein class) is first optimised and evaluated in a model system, and then transferred to commercial varieties or other crop species. In this chapter, we discuss practical issues guiding the development of crop-based production systems for molecular farming in plants.

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