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New Approaches in Research with Nanobodies

Smallest antibody fragments, so-called nanobodies, can be used successfully in basic scientific research. The group led by Prof. Markus Affolter at the Biozentrum of the University of Basel has developed a method, in which for the first time nanobodies can be applied to selectively modify and regulate protein functions in living animals. The findings, which have been published in the journal Nature Structural and Molecular Biology, could provide a new approach for the treatment of serious diseases.

While the use of antibodies in research and science as well as in the field of medical therapies has become routine, there is up to date, little application in basic science of so-called nanobodies, tiny antibody fragments originally found in the camel.  Markus Affolter’s research group at the Biozentrum of the University of Basel has now succeeded in functionalizing a nanobody that is directed against GFP (Green Fluorescent Protein) in such a way that it can be successfully employed in fundamental research investigations.  Due to its feature of being able to degrade GFP fusion proteins, the scientists could regulate protein function with the aid of the nanobodies in the living organism. The fruit fly, Drosophila melanogaster, served as a model for testing this method. The findings are important in view of the possibility that in the future protein function in living organisms could be more rapidly and selectively investigated and regulated using nanobodies than with existing conventional methods.

Nanobody vs. Antibody

It is normally not possible to artificially inactivate proteins through antibodies within the cell. This is because antibodies consist of chains of a thousand amino acids, which neither enter cells nor function within the cell. Nanobodies are made up of about 100 amino acids only. This markedly reduced size along with their capacity to fold into functional proteins inside the cell makes nanobodies very interesting for fundamental research. Although they can be used to block protein functions just like antibodies, they have as yet received little attention in basic science. Through a genetically steered procedure, Emmanuel Caussinus from the Affolter research group has now developed a method, which helps nanobodies to be coupled to other functions. This enables proteins in living organisms to be selectively controlled and regulated through synthetically produced GFP-Nanobodies. Nanobodies could become increasingly important not only in research but also for therapeutic purposes.

Treatment Possibilities with Nanobodies

Proteins are a main component of all living things and uphold all vital functions in the body.  Defective proteins can lead to disease. As part of the immune response, the body calls on antibodies it produces itself to fight pathogenic intruders. They are a central component of the immune system and can selectively turn off defective proteins according to the lock and key principle.
In medicine, synthetically produced antibodies are also frequently used in the treatment of diseases such as asthma, rheumatic disorders or cancer. The synthesis of such antibodies is however a very complex and expensive process. Nanobodies could in the long term replace the use of such synthetic antibodies not only in research but also in the treatment of diseases. Their implementation could also make therapies possible, which are targeted at the regulation of cellular proteins, an application that is not possible with conventional antibodies.

Original article:
Emmanuel Caussinus, Oguz Kanca & Markus Affolter (2011): Fluorescent fusion protein knockout mediated by anti-GFP nanobody. Nature Structural and Molecular Biology, Published online 11 December 2011.

Contact: Communications, Heike Sacher