Knowledge of how DNA and RNA interacts with lipids is central to the understanding of organization and function of these molecules in biological systems. Moreover it is important for drug delivery formulations involving nucleic acids as well as synthetic biology and nano biotechnology. We have found that not only charge controls the interaction, but also hydrophobic interactions play an important role. In order to determine the effect of bilayer fluidity on RNA orientation at an oppositely charged bilayer aqueous interfaces was studied. We have studied the in the interaction between the ssRNA and its complementary strand to reveal the orientation of RNA.1 Here we found that the “hydrophobic” bases penetrate into the lipid acyl-chain region of the bilayer if they are in liquid state and hence prevents base-pairing. We also found that supra-molecular assembly of negatively charged 3D RNA polyhedrons can be formed on cationic fluid lipid bilayer scaffolds.2 The stepwise supramolecular assembly of tectosquare building blocks, through specific and selective RNA-RNA interactions was followed in situ by ellipsometry and QCM-D. Formation of a single and densely packed surface layer of RNA polyhedrons was found due to the fluidity lipid bilayer. Gene therapy requires that the large hydrophilic highly (negatively) charged DNA crosses the lipid membrane. This can be achieved by forming complexes with poly(amido amine) (PAMAM) dendrimers, which have previously been shown to have potential use in drug and non-viral gene delivery applications. We have studied formation of such complex and how dendrimers can be translocated across both a zwitterionic and an anionic model membrane.3 4