Frank Buchholz is full Professor for Medical Systems Biology and Head of Translational Research at the University Cancer Center (UCC) of the TU Dresden. As a PhD student, he performed seminal work to implement and improve site-specific recombinases for genome engineering. During his postdoctoral time, he showed for the first time that these enzymes can induce a predefined chromosomal translocation in vivo and he invented substrate-linked directed evolution to breed recombinases with novel specificities. He perfectionated this approach as an independent Group Leader at the MPI-CBG to develop the Tre recombinase, an enzyme that can eradicate HIV from infected cells. This totally new anti-retroviral approach has been widely recognized as a break-through in enzyme engineering and offers a new strategy for the development of an HIV-cure strategy. Frank is currently extending this approach as a platform technology, making it possible to apply designer-recombinses for a wide range of genetic diseases. Frank is also widely known for his development of the esiRNA technology and its implementation as an efficient and specific RNAi screening tool. Employing this tool, he has discovered many new genes relevant for stem cell biology and human diseases, including the discovery of a genetic link between p53 and snoRNP assembly. His group has extended functional RNAi profiling to primary cells, with the goal to apply this technology to personalized medicine. In addition, Frank extended his genomic research in applying CRISPR/Cas9 technology and could show that CRISPR/Cas9 can be utilized to inactivate cancer driver mutations.