E. Dauty et al., Dimerizable cationic detergents with a low cmc condense plasmid DNA into nanometric particles and transfect cells in culture, J AM CHEM S, 123(38), 2001, pp. 9227-9234
The size of condensed DNA particles is a key determinant for in vivo diffus
ion and gene delivery to cells. Gene molecules can be individually compacte
d by cationic thiol detergents into nanometric particles that are stabilize
d by oxidative conversion of the detergent into a gemini lipid. To reach th
e other goal, gene delivery, a series of cationic thiol detergents with var
ious chain lengths (C-12-C-16) and headgroups (ornithine or spermine) was p
repared, using a versatile polymer-supported synthetic strategy. Critical m
icelle concentrations and thiol oxidation rates of the detergents were meas
ured. The formation and stability of complexes formed with plasmid DNA, as
well as the size, xi -potential, morphology, and transfection efficiency of
the particles were investigated. Using the tetradecane/ornithine detergent
, a solution of 5.5 Kpb plasmid DNA molecules was converted into a homogene
ous population of 35 nm particles. The same detergent, once oxidized, exhib
ited a typical lipid phase internal structure and was capable of effective
cell transfection. The particle size did not increase with time. Surprising
ly, the gel electrophoretic mobility of the DNA complexes was found to be h
igher than that of plasmid DNA itself. Favorable in vivo diffusion and intr
acellular trafficking properties may thus be expected for these complexes.