Eb. Dizhe et al., Receptor-mediated transfer of DNA-galactosylated poly-L-lysine complexes into mammalian cells in vitro and in vivo, BIOCHEM-MOS, 66(1), 2001, pp. 55-61
With the goal of developing non-viral techniques for exogenous gene deliver
y into mammalian cells, we have studied receptor-mediated gene transfer usi
ng complexes of plasmid DNA and galactosylated poly-l-lysine, poly( L-Lys)G
al. To evaluate the optimal parameters for efficient gene transfer into hum
an hepatoma HepG2 cells by the DNA-poly(L-Lys)Gal complexes, the bacterial
reporter genes lacZ and cat were used. Examination of the reporter gene exp
ression level showed that the efficiency of DNA delivery into the cells dep
ends on the structure of DNA-poly(L-Lys)Gal complexes formed at various ion
ic strength values. The efficiency of DNA transfer into the cells also depe
nds on DNA/poly(L-Lys)Gal molar ratio in the complexes. Plasmid vector carr
ying human apolipoprotein A-I (apoA-I) gene was injected as its complex wit
h poly(L-Lys)Gal into rat tail vein. Some level of ApoA-I was detected in t
he serum of the injected rats. Also, the human apoA-I-containing plasmid wa
s found to be captured specifically by the rat liver cells and transported
into the cell nuclei, where it can persist as an episome-like structure for
at least a week. After repeated injections of DNA-poly( L-Lys) Gal complex
es, the level of human ApoA-I in rat serum increases, probably due to accum
ulation of functional human apoA-I gene in the liver cell nuclei. The data
seem to be useful for the development of non-viral approaches to gene thera
py of cardiovascular diseases.