Magnetic microbubble mediated vascular gene transfer for prevention of endothelial dysregulation during insulin resistance

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

Gene targeting of the vasculature offers numerous therapeutic possibilities as conditions associated with vascular dysfunction, such as insulin resistance or type 2 diabetes mellitus, foster vascular disease and thus represent a great socioeconomic problem. By associating therapeutic lentiviral particles or plasmid DNA to magnetic microbubbles and their trapping and rupture at a specific site using external magnetic fields and ultra sound the side effects of systemic gene therapy are reduced and gene transfer efficiencies enhanced. The tyrosine phosphatase SHP-2 regulates PI3-K/Akt and MAPK pathway activation, which is disturbed in insulin resistance, upon growth factor stimulation and influences angiogenesis. The aim of this study is to investigate whether SHP-2 is involved in endothelial insulin signalling and if modulation of SHP-2 can be used to restrict the endothelial dysfunction and its consequences on angiogenesis and vascular inflammation in insulin resistance. This shall be achieved by using the technique of site-directed magnetic microbubble assisted gene delivery of mutant forms of SHP-2 in the vasculature in vivo.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 917: Targeting von Gen- und Zellbasierten Therapien mittels Magnetischer Nanopartikel
• Beteiligte Person: Professor Dr. Florian Krötz