The ASK chip enables the parallel inhibition of all human protein kinases by means of RNA interference on a miniaturised Biochip. This technology allows simultaneous determination of the function of all protein kinases, e.g. growth of tumour cells to identify starting points for new therapies.
Members of the protein kinase family are considered as promising targets for therapy of different diseases. More than 500 protein kinases, which pass on cell signals and affect almost all biological processes, are currently known. A number of these kinases are suspected to play a central role in various diseases such as cancer, inflammation, or cardiovascular disease.
"Until now, however, an overall picture and understanding of this network that would allow e.g. to determine the effects of drugs on the interaction of the protein kinase network is still missing," said Dr Michael Kubbutat, head of research and development at ProQinase.
The collaboration will be supported, in the next three years, by approximately €2 million within the scope of the BioChancePLUS Program of the German Federal Ministry of Research (BMBF).
"By combining Biochip, siRNA, and antibody technologies, this project represents a new scientific approach and validates the efficiency of automation systems for high-throughput antibody generation," stated Dieter Lingelbach, general manager of Antibodies by Design and senior vice president of MorphoSys.
Drug research in this field requires optimised reagents. Sufficient quantities of recombinant protein kinases, methods for specific manipulation of protein expression in suitable cell lines, and kinase-specific antibodies for the entire kinome play a central role.
Currently, the majority of kinases have no antibodies available, creating a bottleneck in the project that will be dealt with by MorphoSys' HuCAL technology. Antibodies by Design will generate recombinant antibodies against up to 250 protein kinases.
The antibody-generating HuCAL technology allows specific recombinant antibodies to be produced faster than existing animal based methods. The technology allows high-level expression of protein fragments for screening against the HuCAL Gold library using bioinformatic algorithms to select antigen sequences for expression and screening.
Targeted blocking of the expression of selected protein kinases will be achieved using short interfering RNA molecules (siRNA) in the form of short hairpin RNAs (shRNA).
These shRNA vectors will be produced by NMI and MorphoSys. ProQinase will use kinase-specific antibodies from Antibodies by Design to confirm deactivation of the protein kinases by specific shRNA vectors.
The combination of all components to create a complete analysis system in chip format will take place at the NMI, where adenoviruses expressing functionally validated shRNA sequences will be arranged on a miniaturized biochip.
"A new approach enabling parallel functional analysis of all human protein kinases in living cells in combination with miniaturization via chip technology has not yet been developed," said Dr Enzio Müller, director of the institute at the NMI.
"We predict a good potential market for the products developed out of this partnership."