Green factories for biopharmaceuticals.

Plants and plant cells have been used to produce many diverse and valuable recombinant proteins, including subunit vaccines, antibodies and antibody fragments, hormones, blood products, cytokines and enzymes. Different plant species and platforms have been explored as production hosts, each with unique properties in terms of production timescales, environmental containment, scalability, downstream processing strategy and overall costs. Whole plants are suitable for the economical and safe production of recombinant proteins on a large scale, providing unique advantages for pharmaceutical proteins that are required in large amounts and normally too expensive for conventional manufacturing processes. Seed-based systems have additional advantages because they exploit the natural storage properties of seeds to facilitate batch processing and distribution. The stabilizing effect of seeds after harvest allows recombinant subunit vaccines and antibodies to be delivered via the mucosal route as they are better able to withstand the harsh microenvironment when protected by the plant matrix. Although the differences between plant and human N-glycans were initially thought to limit the therapeutic potential of plant-derived glycoproteins, several such products have now been tested in the clinic and in some cases the presence of plant glycans has been turned into an advantage because they improve the performance of the protein or confer unique characteristics. In this review we discuss recent case studies of recombinant pharmaceuticals produced in plants to demonstrate the versatility and unique advantages of molecular farming and the bottlenecks that remain to be addressed.