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European BioPharmaceutical Review
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| Michael Liss and Ralf Wagner at GENEART report on current developments in the field of directed evolution as tools for rapid and successful protein improvement
Nearly all objects we consider to be complex are manmade and the result of a rational target-oriented design. Conversely, natural living organisms greatly surpass technical items in terms of complexity without being rationally constructed. They are the result of a long history of evolution, lacking any conscious plan. The strong ‘creative’ force behind this development was recognised some 150 years ago, and became known as Darwinian evolution. The basic principle for the rise of increased complexity and adaptation to a given environment through this process is based on three simple prerequisites: replication, mutation and selection. This strategy is, in fact, so powerful that it outperforms today’s capabilities for rational design by some distance.
Most complex functions of an organism are controlled by proteins: sub-microscopic nanomachines which fulfil their function through a unique three-dimensional structure defined by a specific sequence of 20 different amino acid building blocks. With today’s analytical tools it is easy to determine the amino acid sequence of a protein. It is also possible to resolve the spatial structure of a protein. Still, there is a missing analytical link between sequence and structure as it is not possible to deduce one feature from the other. This is caused by the mathematical complexity of the protein folding problem (attainment of three-dimensional structure) and limitations in today and tomorrow’s computer power.
Proteins are becoming increasingly important in many areas of industry. Pharma exercises demands for recombinant therapeutic proteins with an estimated annual market value in 2008 of US$70 billion to fight anaemia, haemophilia, multiple sclerosis, leukaemia and viral infections, to mention just a few (Frost & Sullivan, BioPharm International, WestLB Equity Research). Food industry uses proteins for baking, juice production, brewing, dairy applications and others. Enzymes (catalytic proteins) are common ingredients in modern detergents and are widely used in pulp and paper processing, textile production and animal feed additives. |
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Dr Michael Liss is a Senior Scientist at GENEART, responsible for the development of new types of synthetic combinatorial libraries and new screening approaches. He has been in charge of the production and quality control of several hundred synthetic libraries. Michael has gained experience in the field of aptamer selection in the laboratory of Dr Larry Gold and received his PhD in Molecular Virology from universities in Boulder, Colorado and Regensburg, Germany.
Professor Dr Ralf Wagner is initiator of the company foundation. He is responsible for GENEART’s company policy and all R&D activities. In addition, he heads the Molecular Microbiology and Gene Therapy Unit at the Institute for Medical Microbiology and Hygiene, University of Regensburg. Ralf is a renowned scientist and has more than 20 years’ practical and theoretical experience in various fields of microbiology, immunology and vaccine development. He holds several international patents and is author of numerous scientific publications. As consultant and expert reviewer he supports the German Research Association (DFG), the German Ministry of Health and Education, the EC and several international foundations. |
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