Kristian M Muller
Bielefeld University, Germany
Title: Recombinant adeno-associated viruses (rAAV) retargeted for cancer therapy
Biography
Biography: Kristian M Muller
Abstract
Virus-based suicide gene therapy with enzymes also called virus-directed enzyme mediated prodrug therapy (VDEPT) delivers genes for prodrug-activating enzymes to tumor cells. This approach leverages modular design of various cellular and transcriptional targeting and detargeting approaches with established enzyme-prodrug combinations. We are testing EGF-receptor dependent gene delivery by fusing binding domains (DARPin, Affibody) to capsid proteins or by inserting computationally designed peptides into capsid loop structures. For prodrug activation, we utilize thymidine kinase or cytosine deaminase in combination with ganciclovir or 5-fluorouracil, respectively. At cellular level, we achieve tumor-marker specific binding, transduction and ultimately specific killing. The approach is facilitated by a modular vector design and the use of fluorescent proteins as genes of interest. Effects on target cells were analyzed by viability assays as well as microscopy and flow cytometry.