Nucleic Acids Research, Vol 27, Issue 19 3792-3798, Copyright © 1999 by Oxford University Press
P Kreiss, B Cameron, R Rangara, P Mailhe, O Aguerre-Charriol, M Airiau, D Scherman, J Crouzet and B Pitard
Clinical applications of gene therapy mainly depend on the development of
efficient gene transfer vectors. Large DNA molecules can only be
transfected into cells by using synthetic vectors such as cationic lipids
and polymers. The present investigation was therefore designed to explore
the physicochemical properties of cationic lipid-DNA particles, with
plasmids ranging from 900 to 52 500 bp. The colloidal stability of the
lipoplexes formed by complexing lipopolyamine micelles with plasmid DNA of
various lengths, depending on the charge ratio, resulted in the formation
of three domains, respectively corresponding to negatively, neutrally and
positively charged lipoplexes. Lipoplex morphology and structure were
determined by the physicochemical characteristics of the DNA and of the
cationic lipid. Thus, the lamellar spacing of the structure was determined
by the cationic lipid and its spherical morphology by the DNA. The main
result of this study was that the morphological and structural features of
the lipopolyamine- DNA complexes did not depend on plasmid DNA length. On
the other hand, their gene transfer capacity was affected by the size of
plasmid DNA molecules which were sandwiched between the lipid bilayers. The
most effective lipopolyamine-DNA complexes for gene transfer were those
containing the shortest plasmid DNA.
ARTICLES
Plasmid DNA size does not affect the physicochemical properties of lipoplexes but modulates gene transfer efficiency
UMR 133 Centre National de la Recherche Scientifique-Rhone Poulenc Rorer, Vitry sur Seine, France.
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