Molecular Farming of Antibodies

The applications for recombinant antibodies in healthcare are increasing. Being able to produce them on a large scale in plants will make them more affordable, which, in turn, will increase their availability to treat a greater number of diseases than is possible at present.

The contribution of Schillberg and Twyman focuses on the critical molecular factors for antibody expression in plant cells. Expression levels depend on both the structure of the chosen recombinant antibody and where it will be expressed within the organelles of eukaryotic cells. For example, most antibodies are poorly expressed in the cytoplasm of plant cells, but targeting them to the secretory pathway, and especially retaining them in the endoplasmic reticulum, results in higher production levels. The authors review both transgenic plants and cultured suspension cells as production systems for antibodies. The most interesting aspect of plant suspension cells is that they are a biologically contained system, which has advantages for the production of recombinant proteins under controlled conditions.

Antibodies are a diverse family of proteins and it is clear that some forms will have advantages over others in the context of plant-based expression. In addition to their role as pharmaceuticals, one attraction of antibodies is that they can be used to create disease-resistant plant lines. Schillberg and Twyman have pioneered the use of membrane-anchored antibodies to generate plant lines resistant to viral infection and—while this is not molecular farming per se—it demonstrates that antibody expression is, in itself, a useful tool for the improvement of plant characteristics.

Perspectives for Molecular Farming

In bringing these authors together, we have provided a snapshot of molecular farming. It is clear that there is still no consensus on the optimal production system for recombinant proteins in plants. This reflects, in part, the practicalities of the intellectual property situation in molecular farming. However, it is our opinion that consensus will eventually be determined by industry. We believe this to be the case because it will be industry that will commercialise molecular farming, not academic research laboratories. Industry will determine the commercial system that is the most appropriate and financially viable, and this decision will drive the progress of molecular farming.

Public acceptance of molecular farming and plant biotechnology is an issue that we have not discussed here, as our goal is to present an account of the state of the art in this field. We feel that success is the most powerful argument that can be used in favour of the technology. The contributions show that we have made significant progress towards that end. When the first protein from molecular farming is released into the market-place, and patients’ lives are seen to improve as a result, the public will then judge the technology on the basis of its benefits. We estimate that we are 2 to 4 years from that moment.

As with all new technologies, practical problems need to be overcome. Many of these, such as the difference between protein glycosylation patterns in plants and animals, have been discussed in detail in these contributions. We believe that, once defined, these challenges can all be solved. Advances in fundamental research, such as controlling gene silencing or chloroplast-targeted protein expression, will provide benefits for molecular farming. Although fundamental research remains the key tool available for improving the technology, molecular farming is already well advanced and close to product commercialisation.

The last decade has seen dramatic progress in plant biotechnology and this has led to the development of molecular farming. The next decade will see products approved as pharmaceuticals and once this happens molecular farming will finally have come of age.

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