(a) The unit cell of the double-gyroid cubic phase (space group Ia3d) incorporating siRNA within its two water channels (green and orange). The structure was deduced by synchrotron x-ray scattering. For DOTAP/GMO–siRNA complexes the phase (labeled QIIG, siRNA) is observed for GMO (1-monooleoyl-glycerol) molar fractions (ΦGMO) between 0.75 and 0.975. A lipid bilayer surface separates the two intertwined but independent water channels. The bilayer is represented by a surface (grey) corresponding to a thin layer in the center of the membrane as indicated in the enlarged inset. (b) Total (KT, black lines and symbols) and nonspecific (KNS, red lines and symbols) gene knockdown for DOTAP/GMO–siRNA complexes (squares) and DOTAP/DOPC–siRNA complexes (circles) as a function of mole fraction of neutral lipid (ΦNL). DOTAP/GMO–siRNA complexes in the gyroid cubic phase (QIIG, siRNA) at low cationic lipid content (ΦGMO ≥ 0.75) show remarkably improved sequence-specific gene silencing over complexes in the lamellar phase (LαsiRNA). Reprinted with permission from reference 76. Copyright 2010, American Chemical Society.