FA0804

Molecular farming

Plants as a Production Platform for High Value Proteins

Reasons for the Action

Significant progress has been made over the years in MF, and it has been shown that plants can provide a unique opportunity for economic and safe production of commercially valuable complex proteins, amongst which important pharmaceuticals used for human health. This guiding principle will be a key driver for further development of the technology in Europe over the next 25 years, as discussed in the European Technology Platform vision document "Plants for the future" and in the corresponding Strategic Research Agenda (SRA). Five years ago, the tandem baculovirus/insect cells was a widely practiced and efficient lab tool - today, it is a validated production host that proved itself valuable for antigens for human vaccines (GSK, Protein Sciences) and more useful applications are coming. This is where plant-factories stand today, at the dawn of product approval for human and animal therapeutics. It is worth noting this is one of the fields where Europe excels, and where continued investment is the most likely to produce exemplary scientific and societal results.

1. As higher eukaryotes, plant cells resemble mammalian cells in possessing an endomembrane system, that allows the folding, assembly and post-translational modification of complex proteins (this is often not possible with prokaryotic cells).

2. Plants are easy, versatile and economical to grow.

3. The latest expression technologies in plants allow very rapid production of large amounts of recombinant protein. This speed and scale of production now rivals the capacity of the best conventional technologies currently available.

4. Scale-up technology is available for harvesting and processing plants or plant products on a large scale.

5. The purification requirement is simplified. It is possible to use only partially processed plant products if the recombinant protein is used topically or orally.

6. Plants are not infected by potential human pathogens, e.g. prions or viruses. This significantly reduces production costs, and eliminates health hazards.

Ultimately, plants represent versatile expression systems for a wide variety of recombinant proteins, and they offer rapid and economical production scale-up. Early experiments were carried out in model plant species, such as Arabidopsis and tobacco, but important crop plants (e.g. rice, corn, barley and other crops important for European agriculture) with well established agronomic, harvesting, transport, storage and processing practices, have now been shown to be effective production platforms. Furthermore, plant cell cultures can offer another alternative production system.

In order to maximize the potential of MF to deliver valuable products that take advantage of specific needs or market opportunities, like affordable medicines to developed and developing countries, a number of hurdles need to be addressed. A virtual co-ordination centre will be established, in which all the major European players in this field can join. Through this centre, efforts in key areas such as dedicated infrastructures for plant biomass production, manufacturing, downstream processing, purification, product validation and quality control, clinical trials, IP and regulatory issues will be coordinated by this Action in order to sustain and broaden the scientific basis of European plant research. In addition, an element dealing with co-development of plant MF in developing countries is incorporated. The centre will also act as a first port of call for anyone interested in MF, from within or outside the EU, from industry, academia or any other agency.

The outcome of the Action will be a sustainable European plant MF community with clear frameworks for regulatory, biosafety and IP issues. Eventually the Action will allow the establishment of a European Committee of Molecular Farming. This Committee would be established in order to influence policy in Europe for MF in a more positive direction, which would guarantee the continuity of this COST Action in the fast developing field of complex recombinant proteins, including biopharmaceuticals.

In addition the Action will create new opportunities for European agriculture and horticulture and the related technology sectors as the plants dedicated to MF constitute new high-value crops that may generate significant investments in modern greenhouses and agricultural systems.

Although the funding of members of this Action is secured from national or EU resources the Action will nevertheless endeavour to engage and involve key institutions from developing countries, at least by opening our annual WG meetings or workshops to them. The attempt is to solicit additional funding for this purpose from national and philanthropic agencies and organizations committed to improving the quality of life and living standards in the developing world. Through the identification of lead institutions in particular geographical areas, the Action could be expanded to accomplish this objective.

One of the first activities of this Action will be the establishment of a Road Map as a tool to facilitate productive joint research among the groups. A preliminary inventory of activities and fields of expertise of the participants to this Action show promising future trends in MF. At first glance, a rich and diversified toolbox is available. A second lecture shows that at least half of the groups have a clear orientation toward a family of products. With minimal coordination, the Action will form three to five groups of interest, each developing a product-specific production-platform to answer unmet-medical needs (e.g. oral-administration vaccines and antimicrobials; enzymes; efficient allergens; antibodies). In addition, the Action will allow collaborating in pioneer work on targeting, control of plant-produced recombinant proteins and characterization, essential building blocks for an eventual third generation of product classes.