Dimerizable detergents as gene transfer vectors

Cationic lipids are efficient vectors for DNA delivery in vitro. However, they condense DNA into large polymorphic particles, which severely limits their in vivo performances due to size-restricted diffusion. In contrast, detergents are capable of collapsing DNA into smaller particles but do not mediate cell transfection per se. We have succeeded in retaining the interesting features of both types of amphiphiles in a two-step process leading to monomolecular DNA particles stable in physiologic medium. Anionic DNA molecules were first individually condensed with a designed cationic cysteine-based detergent. The resulting small particles were then stabilised by spontaneous thiol dimerization of the cysteine-detergent into a cystine-lipid on the template DNA. Laser light scattering as well as electron microscopy revealed 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 internal structure could be obtained. Their in vitro cell, transfection properties compare favourably with those of Lipofectamine and PEI.