Dimerizable cationic detergents with a low cmc condense plasmid DNA into nanometric particles and transfect cells in culture

Citation
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
Citations number
29
Categorie Soggetti
Chemistry & Analysis",Chemistry
Journal title
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN journal
00027863 → ACNP
Volume
123
Issue
38
Year of publication
2001
Pages
9227 - 9234
Database
ISI
SICI code
0002-7863(20010926)123:38<9227:DCDWAL>2.0.ZU;2-C
Abstract
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.