Delivering a missing gene or a functional substitute of a defective gene has the potential to revolutionize current medical care. Of the two gene delivery approaches, viral and synthetic vectors, synthetic cationic vectors possess several practical advantages but suffer from poor transfection efficiency. A new approach to gene delivery using charge-reversal amphiphiles is described. This synthetic vector transforms from a cationic to an anionic amphiphile intracellularly. This amphiphile performs two roles: first, it binds and then releases DNA, and second, as an anionic multicharged amphiphile, it destabilizes lipid bilayers. A charge-reversal amphiphile was synthesized and fully characterized, including the supramolecular complex it forms with DNA. Enhanced gene transfection was observed using these vectors compared to current cationic amphiphiles.
Binary mixtures of fluorocarbon and hydrocarbon nonionic surfactants derived from the tris-(hydroxymethyl)acrylamidomethane (THAM) have been examined by 19 F NMR spectroscopy and UVvisible spectroscopy in the presence of pinacyanol chloride as a probe. Aqueous solutions have been studied as a function of total surfactant concentration over a range of fluorocarbon/hydrocarbon ratios. For molar fractions in fluorinated surfactant lower than 0.7, the variations of both the 19 F chemical shift and of the absorbance show two inflection points as a function of surfactant concentration. This was assigned to two critical micelle concentrations (cmc's). Above the second cmc, two kinds of micelles (fluorocarbon-rich and hydrocarbon-rich) should coexist as a result of the incompatibility between the two types of surfactants. The experimental results cannot be adequately described by current models on demixing micellar systems. An explanation of this behavior is suggested, by taking into account the interactions between the polyhydroxylated headgroups of the surfactants.
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