The expression of recombinant proteins in microbial, animal and plant cells is a fundamental approach in molecular biotechnology. Other innovative research areas include the the production of novel antibody-based pharmaceuticals and development new varieties of plants without genetic engineering.
The Fraunhofer-Gesellschaft founded the Department of Molecular Biotechnology at the former Fraunhofer Institute for Environmental Chemistry and Ecotoxicology (IUCT) more than 15 years ago to increase its competence in biotechnology. Just two years later, the department was so successful that a new division was established with several additional departments, and the Institute was renamed the Fraunhofer Institute for Molecular Biology and Applied Ecology IME. The institute has a mission to develop product candidates and innovative solutions for the diagnosis and treatment of human and animal diseases, as well as new technologies for the agricultural and food/feed industries. The Fraunhofer IME focuses on application-oriented research in molecular biotechnology, which embraces its ties with industry.
Recombinant therapeutic proteins and protein-based vaccines play an increasingly important role in modern medicine. The latest data from the German Association of Research-based Pharmaceutical Companies show that over 215 biopharmaceuticals produced by genetic engineering are now approved in Germany, and they represent approximately 21 per cent of all domestic pharmaceuticals sold. Another 587 biopharmaceutical preparations are currently undergoing clinical development.
Traditionally, these proteins are produced in bacteria or mammalian cells. The Fraunhofer IME is developing plants and plant cell cultures as alternative production platforms in order to satisfy the growing worldwide demand for affordable recombinant proteins. Fraunhofer IME researchers have pioneered the development of plant-derived pharmaceuticals in Europe. Plants are converted into protein factories by inserting the genes for protein-based medicines and the biopharmaceutical proteins can be extracted and purified from plant tissues quickly, efficiently and safely. Tobacco plants are particularly suitable as protein factories because genetic engineering is simple and they produce large amounts of biomass.
The EU project Pharma-Planta involved the use of tobacco leaves to produce an antibody that can protect humans against infection with HIV. The antibody binds to a protein on the surface of the virus and prevents the virus from interacting with its normal target – human immune cells. A total of 800 kilogrammes of plant material was processed at the Fraunhofer IME greenhouse so that enough of the antibody could be purified for a phase I clinical trial, to the standards required by the European Medicines Agency. The trial was carried out by partners at St. George’s Medical School in London and at the University of Surrey Clinical Research Centre, confirming the safety of the plant-derived antibody. A phase II clinical study is now being developed under a current ERC project which will see the antibody tested in humans.
Insects are the most successful group of organisms in evolutionary terms and there are more than one million species occupying diverse habitats. The Fraunhofer IME facility in Gießen is carrying out pioneering work on the applications of insects in the biotechnology industry, in association with the Justus Liebig University at the LOEWE Center for Insect Biotechnology and the Bioresources & Technische Hochschule Mittelhessen University of Applied Sciences. The team is led by Prof. Dr. Andreas Vilcinskas and is looking at the applications of insects in red (medical), green (agricultural) and white (industrial) biotechnology. Research in the field of red biotechnology includes the development of new antibiotics to treat multidrug-resistant bacteria, which are becoming more prevalent worldwide and are responsible for most hospital-acquired infections. For example, a protein expressed by the larvae of the greater wax moth has been found to inhibit virulence factors in bacteria of the genera Clostridium, Pseudomonas and Vibrio. Its structure and function were formerly unknown but it is now being developed into a novel antibiotic lead structure.
Research in the field of green biotechnology includes the investigation of insect-derived peptides that kill the fungal parasites of plants. Fungal diseases cause catastrophic crop losses all over the world. Useful molecules come not only from the insects themselves, but also from their associated microbes, providing a valuable yet underexploited resource for new plant protection products.
The growing world population is becoming more industrialised. It relies on finite resources for the production of energy, chemicals and materials, and produces large amounts of waste. It would be beneficial to use industrial waste for the production of raw materials and energy because it is abundant and inexpensive and often regarded as a pollutant. The Fraunhofer IME Industrial Biotechnology Department is addressing this challenge by developing strategies for the conversion of syngas (a mixture of carbon monoxide, hydrogen and carbon dioxide produced as waste from power stations and heavy industry) into useful fuels and chemicals using microbial fermentation. To achieve this, rod-shaped bacteria from the genus Clostridium are genetically modified to convert syngas into valuable chemical building blocks such as isoprene and hexanol. Other projects are looking at ways to convert biomass for the same purpose. Ultimately, these research activities could develop ways to convert biological and industrial waste into biofuels for the motor and aviation industries, as well as inexpensive sources of fine chemicals.
The author is the director of the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and professor of Molecular Biotechnology at RWTH Aachen University. He has written over 250 publications and 47 book chapters, has 37 issued patents and more than 50 patent applications. In 2012, Prof. Fischer received an Advanced Grant from the European Research Council ERC, which is awarded to particularly excellent and experienced researchers.