The first commercial products from chloroplast transformation technology (CTT) looks a distinct possibility after Chlorogen signed a joint development and supply agreement with Sigma-Aldrich to produce four specific proteins in tobacco plants to be used in applications as active pharmaceutical ingredients.
Interest in using plants as biological production systems comes from theoretic advantages over commonly used systems such as Escherichia coli and yeast, including the ability to make a broader range of proteins with more complex modifications.
However, the use of plant cells has historically been held back by limitations in getting expression levels to a level that makes plant production commercially viable, and it is this obstacle that the new alliance hopes to solve.
The collaboration's ambition is to see CTT revolutionise plant-derived protein production by greatly increasing the protein output of plants, as well as providing safety and cost advantages over material produced from animal derived cells, while significantly lowering the cost of pharmaceutical production.
Current methods introduce genes into the plant cell nucleus to produce beneficial proteins and pharmaceutical proteins. CTT however, introduces a new gene into approximately 100 chloroplasts within a plant cell. Each chloroplast contains about 100 copies of the plant's genetic structure.
Therefore, chloroplast transformation can produce about 10,000 copies of the introduced gene per plant cell as opposed to only one or two via nuclear transformation. There is also an environmental advantage, because chloroplasts, which are inherited maternally, are not functional in tobacco pollen and cannot be transferred to conventional tobacco via pollen.
Under the terms of the agreement, Sigma-Aldrich will fund an undisclosed portion of Chlorogen's work and represents the first time Sigma-Aldrich has funded the R&D of transformed plants for large-scale production of reagent proteins. The two companies expect to share the revenues from the finished protein products.
Prior to this agreement, the company's involvement in the transgenic plant market has focused on the purification of proteins from biomass on a contract manufacturing basis as well as acting as a sales and marketing outlet for novel proteins.
Tom Gelineau, director of new business development at Sigma-Aldrich said: "The interest to us is the potential to reduce customer costs and have a viable alternative to animal-derived proteins."
The concept of producing pharmaceuticals in crop plants is an attractive proposition because it could produce vast quantities of drugs or vaccines at low cost, potentially making it possible to make drugs that were not economically feasible before.
A report on the crop biomanufacturing sector, published earlier this year by Bio-Era, found that crop biomanufacturing has significant advantages in production costs over rival systems, as crops are already produced by a 'competitive and efficient agricultural-industrial complex', and the capital needed for new production capacity is much lower than for mammalian culture or fermentation.
This report also revealed that the vast majority of field trials of biomanufacturing in crops - 90 per cent - have been in food plants such as soy, barley, rapeseed, safflower, sugarcane, tomato, and wheat. The reason is that much more R&D has been carried out on manipulating the genes of these crops by the agricultural biotechnology sector compared to non-food crops such as tobacco and alfalfa.
Another consideration is that tobacco and alfalfa need immediate processing after harvesting, while a number of food crops can store the recombinant biomolecule in their seed, allowing it to be stored and shipped before processing.
The Chlorogen/Sigma Aldrich collaboration is not the only partnership that has entered the crop biomanufacturing sector. June of this year saw Germany's Icon Genetics and Israeli firm Protalix collaborate on a way of hiking protein expression in plant cells to improve their use of a production vehicle for recombinant proteins.
Other main players within this sector include Dow Plant Pharmaceuticals, BASF plant science and Bayer CropScience, which have all formed their own crop biomanufacturing capabilities in this $25 billion (€20.3 billion) area of the market.