The purpose of this study was to control the fabrication of new labile supramolecular assemblies by formulating associations of DNA molecules with inorganic layered double hydroxides (LDHs). The results show that LDH/DNA hybrids synthesized by a coprecipitation route involving the in situ formation of LDHs around DNA molecules acting as templates were characterized by a lamellar organization, with DNA molecules sandwiched between hydroxide layers, exhibiting a regular spacing of 1.96 nm. Our results indicate that labile complexes resulting from the association of nucleic acids and inorganic materials can be obtained not only by anion exchange but also by a direct self-assembly route.

RNA interference requires efficient delivery of small doublestranded RNA molecules into the target cells and their subsequent incorporation into RNA-induced silencing complexes. Although current cationic lipids commonly used for DNA transfection have also been used for siRNA transfection, a clear need still exists for better siRNA delivery to improve the gene silencing efficiency. We synthesized a series of cationic lipids characterized by head groups bearing various aminoglycosides for specific interaction with RNA. siRNA complexation with such lipidic aminoglycoside derivatives exhibited three lipid/siRNA ratio-dependent domains of colloidal stability. Fluorescence and dynamic light-scattering experiments showed that cationic lipid/siRNA complexes were formed at lower charge ratios, exhibited a reduced zone of colloidal instability, and had smaller mean diameters compared with our previously described guanidinium-based cationic lipids. Cryo-transmission electron microscopy and x-ray-scattering experiments showed that, although the final in toto morphology of the lipid/siRNA complexes depended on the aminoglycoside type, there was a general supramolecular arrangement consisting of ordered lamellar domains with an even spacing of 67 Å. The most active cationic lipid/siRNA complexes for gene silencing were obtained with 4,5-disubstituted 2-deoxystreptamine aminoglycoside derivatives and were characterized by the siRNA being entrapped in small particles exhibiting lamellar microdomains corresponding to siRNA molecules sandwiched between the lipid bilayers. These results clearly show that lipidic aminoglycoside derivatives constitute a versatile class of siRNA nanocarriers allowing efficient gene silencing.gene silencing ͉ gene transfer vectors ͉ transfection R NAi has become widely used for knocking down the expression of a specific target gene by a posttranscriptional silencing mechanism and thereby it allows phenotypic analysis of gene function in cells (1, 2). Therapeutic approaches involving RNAi are also actively investigated (3, 4). To achieve gene silencing, sequence-specific double-stranded small interfering RNA (siRNA) molecules have to be delivered efficiently into the cytoplasm of cells (5, 6). Various methods have already been used for siRNA delivery, in particular, cationic lipids developed for plasmid DNA transfection (see ref. 7). These cationic lipids are composed of a hydrophobic moiety linked (by a spacer) to a cationic head group bearing either a quaternary ammonium [such as the lipids DOTMA {N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride} and DOTAP (1,2-dioleoyl-3-trimethylammonium-propane)], a polycation [such as the lipid DOGS (dioctadecylamidoglycylspermine) (8) and lipopolyamine RPR120535 (9)], or guanidinium groups [such as the lipid BGTC, bis(guanidinium)-tris(2-aminoethyl)amine-cholesterol (10, 11)]. A colipid such as dioleoyl phosphatidylethanolamine (DOPE) is usually combined with the cationic lipids to form liposomes. The electrostatic interactions between the plasmid D...