Optimized muscle-specific expression and comprehensive characterization of antibody-encoding minicircles for the in vivo production of therapeutic antibodies in mice

In vivo antibody expression via antibody gene transfer is at crossroads between antibody and gene therapy. Following administration of the DNA that encodes a therapeutic antibody, the site of delivery, e.g. muscle, is turned into an antibody 'factory’, resulting in the presence of antibodies in the blood for a prolonged period of time. This innovative approach addresses several challenges associated with conventional antibody proteins, such as the high production cost, need for longterm repeated administrations, and patient discomfort. The Laboratory for Therapeutic and Diagnostic Antibodies has previously obtained a proof of concept for non-viral antibody gene transfer in mice. To further advance this approach to the clinic, we recently started working with minicircle vectors that carry the antibody-encoding DNA to target cells. This innovative non-viral vector is derived from plasmids and devoid of bacterial sequences, providing a superior safety and expression profile. The current proposal further builds on the progress the Laboratory made so far and addresses the key challenges this research field still faces. Our main objectives include the design of a strong muscle-specific antibody expression system, the comprehensive characterization of the in vivo expressed antibodies in mice sera, and assessment of minicircle biosafety in mice.