Targeted adenoviral delivery to the heart by magnetic microbubbles and highly focused ultrasound and imaging of gene transfer related processes

• Antragstellerin: Privatdozentin Dr. Martina Anton
• Fachliche Zuordnung: Pharmakologie
• Förderung: Förderung von 2009 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 40403621

Adenoviral vectors have been used for decades in pre-clinical studies and clinical trials. Insufficient gene transfer efficiency has been identified as one of the main obstacles to success in recent late-stage clinical trials of cardiovascular gene therapy. Hence, the major focus of this project is enhancing and focusing adenoviral gene transfer to the myocardium in a rat model by combined magnetic field and ultrasound targeting. Multimodal imaging modalities including ultrasound, MRI and μPET/CT are not only used to image and control the delivery process but also to visualize perfusion, integrin expression as part of remodeling, and the expression of the a delivered reporter gene. Combining these imaging strategies we want to analyze not only the location of delivery, but also the processes that are involved in remodeling after ischemia/reperfusion and possible reduction of damage by therapeutic gene products with anti-inflammatory activity or being involved in vascularization. During the first funding period of this project we have developed optimized nanomagnetic compositions of adenovirus which were highly superior over naked virus in in vitro models under flow conditions and in an oncology therapeutic setting. We have developed a shielding modality which confers some protection of the magnetic virus against inactivating interactions under physiological conditions. Our novel composition of the virus associated with magnetic microbubbles allows for ultrasound guidance of delivery. Based on these fundaments and using reporter genes, an optimized dual targeting and theranostic formulation of adenovirus shall be developed for the delivery of therapeutically relevant genes of the consortium.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 917: Targeting von Gen- und Zellbasierten Therapien mittels Magnetischer Nanopartikel
• Beteiligte Personen: Professor Dr. Christian Plank; Professor Dr. Markus Schwaiger; Privatdozent Dr. Klaus Tiemann