Traditionally, the Oncogenetics section utilizes patient-derived cell models and their cDNA complemented counterparts as isogenic cell models to investigate hereditary cancer genes. As a next step, we are now using CRISPR/Cas-based gene editing to engineer tissue-specific cell models of clinically relevant mutations for functional classification and to study their effects on tumorigenesis in vitro. In addition, we created a genome-wide CRISPR screening pipeline in Cas9-inducible diploid human epithelial cells to screen isogenic models of cancer genes. The aim of this approach is to reveal molecular genetic networks which help us to pinpoint candidate biomarkers and druggable vulnerabilities. We are also performing genome-wide screens in combination with targeted cancer drugs to uncover the drug-sensitizing effects of gene inactivation and putative drug-resistance mechanisms. Building on our growing expertise in CRISPR technology, we are developing applications that allow the use of Cas12 in genome diagnostics. In the future, we hope to explore ways to implement targeted gene editing in therapeutically relevant clinical genetics.
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