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Plant made Pharmaceuticals
Since January 2006 the Bayer Innovation GmbH is engaged in the field of protein expressions in plants (“plant made pharmaceuticals”). Our goal is to become one of the leading providers of proteins for the therapeutic and further needs. The Icon Genetics GmbH (Halle/Saale), which was acquired in 2006, forms the Expertise Cluster "PMP" (Plant made Pharmaceuticals) for Bayer together with experts from Bayer CropScience, Bayer HealthCare AG, Bayer Technology Services GmbH and external collaboration partners.
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| Gene immersion bath: Dr. Sylvestre Marillonnet places tobacco plants upside down in a vacuum tank filled with a bacterial solution. The bacteria transport genes into the plants which are then capable of producing medicinal active substances (left). Alternatively, the active substance genes can be implanted into individual tobacco cells which then grow into whole plants |
‘Pharming’ is the term used by experts to describe the production of high-quality, recombinant proteins in plant biofactories. This is because in future “personalized medicine” could mean an increased demand for small quantities - a problem which cannot readily be solved economically using today’s production processes.
Plants are so closely related to humans and animals that they are able to correctly process and configure complex proteins of human or animal origin. The idea of using plants as protein biofactories is not that new, however. The first pharmacological substance was created in a plant as long ago as 1986. A tobacco plant was modified in such a way that it formed the human growth hormone somatotropin. Three years later, the first antibodies – much more complex proteins than somatotropin - were produced using recombinant technology, again in a tobacco plant.
Since then, scientists have referred to such antibodies as “plantibodies”. In all these experiments, the plant’s DNA was changed in exactly the same way as had previously been done to modify the plant’s properties. With the magnICON technology, the scientists combine the gene for the medical active substances they need with the genetic material of plantspecific viruses. Such viruses multiply rapidly in plant cells. The viruses themselves are used solely as vectors and cannot infect the plants.
Since then, scientists have referred to such antibodies as “plantibodies”. In all these experiments, the plant’s DNA was changed in exactly the same way as had previously been done to modify the plant’s properties. With the magnICON technology, the scientists combine the gene for the medical active substances they need with the genetic material of plantspecific viruses. Such viruses multiply rapidly in plant cells. The viruses themselves are used solely as vectors and cannot infect the plants.
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| Scientist of Bayer's subsidiary Icon Genetics during homogenization of tobacco leaves after harvest at the pilot plant for clinical sample supply. |
In the initial stage, the scientists modify the genotype of a plant virus, the tobacco mosaic virus, from the natural RNA (ribonucleic acid) form to the chemically more stable DNA (deoxyribonucleic acid) form. The desired genes are then incorporated into the DNA and the viral genome modified in this way is introduced into the tobacco cells using bacteria of the Agrobacterium tumefaciens species. The plants subsequently produce the desired substance. To do this, the scientists use not a syringe, but an immersion bath. The plants are dipped upside down as far as the bottom of the stalk into a bacterial solution and exposed to a vacuum. The process takes one or two minutes and then the pressure is slowly brought back to normal. The immersion solution contains Agrobacterium tumefaciens, which is subsequently found in all fully developed leaves on the tobacco plant. The bacterium itself only has one job – to introduce the modified tobacco mosaic virus into the plant. This virus is not complete – the sheath protein is missing, for example. Instead, it has been equipped with genes which enable the plant to produce the desired proteins or active substances after the infiltration. With this method, the plants don’t incorporate the foreign genes into their genotype. They are not transgenic and lose the foreign hereditary information again after a little while.
The treated plants continue to grow under normal greenhouse conditions for a further ten days or so. They recover very quickly from the immersion bath and infection. During this period, they form considerable quantities of the desired products in their cells. The scope of this technology is broad: For example, hormones can be produced, as well as vaccines or enzymes for technical applications. Even antibodies, which play an important part in the immune defense against pathogens by identifying and fighting foreign structures, can now be produced by tobacco plants.
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