The main aim of our project was to find tailor acoustically active liposome-based microbubbles efficient for nucleic acids (NA) transfer.Our challenge was to obtain liposomes that met the following requirements:a) enough gas content and adequate elastic properties for a good acoustic activity; b) able to interact with NA and / or fusion with the plasma membrane at neutral pH;c) capable to mediate escape from acidic endosomes.Amongst different formulations produced, we selected 3 cationic liposomes formulations that contained perfluorobutane gas in the core and made with original DMAPAP or histidylated lipophosphoramidate lipids.These formulations were acoustically active with an acoustic attenuation of-35 dB and a resonance peak between 1 and 1.5 MHz.They were able to interact with different type of nucleic acids without compromising their acoustic properties.What is more, loading with hydrophobic drugs sunch as paclitaxel did not affect those features.They were specifically attracted to cells upon US application as visualized by high-speed camera.Efficient gene, siRNA and mRNA transfer were obtained in vitro.In vivo, we observed gene expression either via local or intravenous injections can extend up to 100 days.Specific liver gene expression was obtained following intravenous administration and used to produce sulfamidase in mouse model for mucopolysaccharidosis type Ⅲ A (Sanfilippo syndrome).