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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.

Biography

Kristian Müller is a professor of cellular and molecular biotechnology at Bielefeld University, Germany. He was an Assistant Professor and Group Leader at the University of Freiburg and the University of Potsdam. Prior to his independent career he has worked as a Postdoctoral Scientist at the University of California at Berkeley and received his PhD from the University of Zurich and Diploma in Biochemistry from the University of Hannover. Within the realm of protein engineering and synthetic biology he performs basic research and develops technology, which he utilizes to drive innovations such as cancer therapeutics.

Email: kristian@syntbio.net