Recombinant in vitro antibody production

Researchers at the University of Braunschweig in Germany are developing and championing a recombinant in vitro antibody production technique, which has the capacity to provide large amounts of research material.

In the wake of human genome sequencing, it would be tempting to believe that science is not far from elucidating the detailed biochemical processes of life. But this is somewhat misleading – while there is no denying that this discovery was a huge and important step, it is not the complete story. The genome consists of genes which code for proteins. Those proteins are themselves subject to multiple modifications which change their structure and, consequently, their function. The genes that code for these proteins are turned off and on by various complex biochemical mechanisms, and the resulting effect is a confusing dynamic continuum between genome and proteome. Although we now have a complete list of human genes, we are far from having a comprehensive catalogue of human proteins and this void has limiting implications for research and therapeutics.

For these reasons, there is a vital need to improve our understanding of the proteins in our bodies. One particular technique called in vitro antibody phage display is now coming to the fore as a tool to overcome this challenge. Antibody phage display has existed as a technique for around 20 years, but has recently enjoyed a resurgence associated with improved efficiency and the efforts of a research team from the University of Braunschweig in Germany, led by Professor Dr Stefan Dübel.

Antibodies are a vital tool for the elucidation of any living organismal proteome. They are target specific and as such can be used to ‘tag’ and thus identify proteins. Furthermore, they are a central component of the immune system – detecting and often neutralising invading pathogens. These characteristics of antibodies make them ideal for the identification of the proteins and molecules in living tissue. Despite this central role in research, the provision of antibodies has been previously limited. Moreover, millions of laboratory animals have to be bred and killed to facilitate the production of antibodies – but the new technique championed by Dübel and colleagues has changed the game: “Antibody phage display exchanges animals for microtitre plates, immunisation with a simple binding assay and production by ascites in swollen bellies of mice with a flask on a shaker,” he explains.

The advantages of the new technique are not limited to saving the lives of countless laboratory mice. The process also allows the production of huge numbers of antibodies in a highly-controlled and specific manner. The team have now supplied this essential research material to many scientists who have successfully used them in a wide range of applications. This progress coupled with the recent expiration of intellectual property patents for the technology should open the flood gates: “We will see an explosion of ideas for novel therapeutic antibodies,” predicts Dübel, with a large part to be played by small, creative companies who will now be able to compete due to lowered costs.

The Braunschweig University team has made notable progress, and will continue to advertise the affordability and reliability of recombinant antibodies, but their research will soon move forwards. The researchers now want to develop the capacity of the single antibody, for example, “by combining human antibodies with human enzymes in fusion proteins”. Dübel believes that such combinations will improve the therapeutic application of biologicals, while limiting adverse effects.

The sequencing of the human genome should be seen as the beginning of a journey rather than a full stop. The techniques being developed and used by Dübel and colleagues have the potential to help elucidate the role of the proteins in our bodies – in future years we may be able to boast the understanding of the entire human proteome with all its interactions, and that would have tremendous implications for both medical and academic understanding.

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