The magnetofection technique is a new approach for site-directed intravital vascular delivery of oligodesoxynucleotides (ODN) and pDNA coupled to magnetic nanoparticles ("magnetofectins", MF) using an external magnet, thereby increasing efficiency and reducing toxicity, as shown in primary human endothelial cells. To exploit these advantages for targeted intravascular transfection in vivo, we injected Cy3-labeled ODN either "locally" (n=4) or "systemically" (n=24). Following local magnetofection using a permanent magnet (0,4T), the vessel yielded high fluorescence, in contrast to control vessels. Systemic injection followed by exposure of the dorsal skin to the same permanent magnet resulted in markedly lower fluorescence within vessel walls. Accumulation of ODN at the target tissue when using an electromagnet (0,9T) was enhanced but not as good as after local magnetofection. When MFs were applied in lipid-based microbubbles and released at the target site by external ultrasound application a fluorescence intensity in target vessels similar to that after local application was observed. Functionality was confirmed by transfection of RFP-Plasmid. These results demonstrate that efficiency of systemic gene delivery can be considerably enhanced when packing the MFs in microbubbles and targeting them by magnetofection.