Dimerizable detergents as gene transfer vectors

Cationic lipids are efficient vectors for DNA delivery in vitro. However, t hey condense DNA into large polymorphic particles, which severely limits th eir in vivo performances due to size-restricted diffusion. In contrast, det ergents are capable of collapsing DNA into smaller particles but do not med iate cell transfection per se. We have succeeded in retaining the interesti ng features of both types of amphiphiles in a two-step process leading to m onomolecular DNA particles stable in physiologic medium. Anionic DNA molecu les were first individually condensed with a designed cationic cysteine-bas ed detergent. The resulting small particles were then stabilised by spontan eous thiol dimerization of the cysteine-detergent into a cystine-lipid on t he template DNA. Laser light scattering as well as electron microscopy reve aled a monodisperse population of spherical particles that were stable for days in physiological conditions. With an appropriate choice of hydrocarbon chain length, monomolecular complexes exhibiting a typical lipid/DNA inter nal structure could be obtained. Their in vitro cell, transfection properti es compare favourably with those of Lipofectamine and PEI.