Within this ERC PoC we developed COMbAT a novel preclinical model designed to express patient-derived mutated genes in melanoma cells in a physiological manner. We presented COMbAT potential for personalized medicine and drug discovery in various conferences and described how it can have profound impact on the future of healthcare. One such example is the use of COMbAT in systematic drug screens aiming to target the exact driver mutations present in melanoma patients. Thus, an accurate and in-depth analysis of melanoma samples for their driver mutations, together with the functional characterization of the driver in its physiological expression levels enables the testing of currents small molecule drugs that are specific to the driver in question for cell growth inhibition as well as resistance to particular drugs. As the system is set up using low passage cell lines derived from melanoma patients, we consider the full landscape of mutations found in a particular patient. In order to modify the driver in question in a specific manner, we developed a construct which adds a tag to the amino or the carboxyl terminus of an endogenously expressed protein via modification of its genomic coding sequence by way of promoter-trap and polyadenylation signal-trap constructs. This approach is mediated by homologous recombination and integration of the tagging cassette in frame with the target gene to be expressed, which is a rare event; thus, only one allele is tagged within each cell. This same construct is being used to KI mutations as well as KO genes that are validated as tumor suppressor genes. We demonstrated the technology viability by patenting the technology through a close co-operation with YEDA the independent technology transfer company of the Weizmann Institute of Science. YEDA will provide valuable guidance on protecting patents arising from the proposed POC.
