Molecular farming and therapeutic food

The production of plant-derived biopharmaceutical products is sometimes named as molecular farming. The word biopharmaceutical is applied to a naturally occurring or modified polypeptide, protein, DNA or RNA product that is to be used for therapeutic, prophylacticor in vivo diagnosticusein humans. The main categories of biopharmaceutical products are recombinant proteins, therapeutic monoclonal antibodies, polyclonal antibodies, non-recombinant proteins and antisense oligonucleotides. Between 1995 and 1999, 15 recombinant proteins, six monoclonal antibodies, two polyclonal antibodies, two non-recombinant proteins and one antisense oligonucleotide were approved by the FDA. By mid-2000 there were between 80–90 biopharmaceuticals in general medical use, and around 500 more were undergoing clinical trials. Major targets of these compounds include cancer, cardiovascular diseases, and infectious diseases. Most of these products have been produced in cultured mammalian cells, bacteria and fungi. Now, the use of plants as alternative production systems is being evaluated since plants are potentially a cheap source of recombinant products (Table6.2).

One possible disadvantage of using plants as bioreactors for biopharmaceuticals is that post-translational modification of synthesised proteins may differ from mammals. However, these modifications are few compared with the differences between mammals and microorganisms that have been commonly used as a source of biopharmaceuticals. There is also the risk of impurities in the plant-derived biopharmaceuticals that may include secondary plant metabolites, pesticides and herbicides. Such impurities could have a direct toxic effect, could affect product stability, or could even have immunogenicity leading to allergic reactions. However, biopharmaceuticals derived from transgenic plants could be safer than those derived from human cells that could be contaminated by human pathogens.


Transgenic plants have already been developed to produce proteins such as enkephalines, α-interferon, human serum albumin, glucocerobrosidase and granulocyte-macrophage colony-stimulating factor. These last two are among the most expensive drugs before their production in plants (Giddings et al. 2000). Rice plants have been engineered to produe α-l-antitrypsin and the product is presently under trial (Giddings et al., 2000). In one case the human somatotropin has been reported to be produced in the chloroplast of a non-food crop such as tobacco (Staub et al., 2000) claiming the additional advantage of biological containment in the field cultivation of this plant.

Among possible proteins to be produced in transgenic plants there have been great efforts to produce antibodies whose therapeutic potential has been largely recognised. Functional antibodies have already been produced in plants and sometimes have been named as plantibodies. Plants have been successfully used to generate complex secretory antibodies that would be of particular benefit for topical immunotherapy in mucoses. This is the case with the production of humanised monoclonal antibodies for immunoprotection against genital herpes (Zeitlin et al., 1998). Moreover, the use of edible plant parts as a source of antibodies opens the door to the possibility of treatment of the mucoses of the gastrointestinal tract.

The development of plants expressing vaccine antigens is another relatively new potential application of plant biotechnology. Vaccines consisting of macromolecules with a protective immune response has a limited use in developing countries, mainly owing to their high cost and low stability. The low requirements of growing plants make their production much cheaper. The expression of vaccines in plant tissues also eliminates the risk of contamination with animal pathogens, make them more stable, and may allow oral delivery if expressed in edible parts of the plants. The first clinical trial with a plant-derived vaccine in 1997 demonstrated the induction of a mucose immune response (Tacket et al., 1998). Potatoes genetically modified to produce a cholera toxin B subunit has been shown to induce antibody production in humans after oral administration (Arakawa et al., 1998). Also, in preclinical animal trials, mice fed with transgenic potato expressing hepatitis B surface antigen results in a primary immune response (Richter et al., 2000). More recently, three plant synthesised antigens of cholera, rotavirus and enterotoxigenic E. coli were expressed in potato and showed a strong immune response in potato-fed mice (Yu and Langridge, 2001). Since it is well documented that delivery of plant-derived vaccine to a mucosal site induces both local and systemic immune responses, the list of plant-derived vaccinogens continues to grow, and includes viral, bacterial, enteric and non-enteric antigens.