Ultrasound and microbubbles-mediated gene transfer ; development of cationic microbubbles

Ultrasound and microbubbles-mediated gene transfer is a controlled DNA delivery technique that is less invasive and more effective at targeted delivery than other currently available approaches. The main limitation of this technique is the low transfection efficiency of the commercially available microbubbles. Cationic microbubbles (MBs) were synthesized with the aim of improving their DNA binding capacity and their gene transfer. Two microbubble families were produced using two kinds of lipids available at the laboratory. The second family of microbubbles showed required properties: a proper stability, a good size distribution and acoustic activity. Zeta potential and DNA binding capacity were not as high as expected. Nevertheless, in vitro sonoporation of HeLa cells using the produced microbubbles resulted in almost 30% of transfection efficiency. We also performed in vivo gene transfer and demonstrated that a stable luciferase expression lasting for two weeks after sonoporation was achieved using our microbubbles