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We sought to exploit glycosylated poly-L-lysine (pLK) to increase the uptake and biological antisense activity of a phosphorothioate oligonucleotide (pt-odn) [pt-odn complementary to the 3' noncoding region of intercellular adhesion molecule-1 (ICAM-1) (odn(ICAM-1))] complementary to the 3'-noncoding region of ICAM-1 in A549 cells. Dose-dependent inhibition of ICAM-1 expression was obtained (IC50 = 500 nM) through treatment of cells with odn(ICAM-1) complexed with pLK carrying fucose residues in the presence of 100 microM chloroquine. Alteration in the charge ratio between fucosylated pLK and pt-odn had a significant effect on the efficacy of inhibition (optimal conditions, charge ratio = 1.1). This effect was also dependent on the number of fucose moieties per pLK. Free pt-odn or pt-odn complexed with nonglycosylated pLK gave no inhibition at concentrations of < or = 2 microM. Two control pt-odn (one was targeted against an unrelated gene not present in these cells, gag(HIV), and the other had a randomized sequence) gave no inhibition of ICAM-1 expression in the presence or absence of pLK carrying fucose residues at concentrations of < or = 2 microM. When complexed with pLK carrying 100 fucose residues, the amount of cell-associated pt-odn was increased by 15-fold compared with the free pt-odn. Nongycosylated pLK also increased the amount of cell-associated pt-odn by >10 fold but did not alter the biological activity. These results demonstrate clearly the potential of glycosylated pLK as a pt-odn transporter.
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
March 1997,
Biochemical pharmacology,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
October 1992,
Annals of the New York Academy of Sciences,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
June 2002,
Pharmaceutical research,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
February 1993,
Anti-cancer drug design,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
April 2004,
Biotechnology and applied biochemistry,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
August 2007,
Pharmaceutical research,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
April 1998,
Journal of controlled release : official journal of the Controlled Release Society,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
June 2001,
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
January 1999,
FEBS letters,
A J Stewart, and
C Pichon, and
L Meunier, and
P Midoux, and
M Monsigny, and
A C Roche
March 1962,
Nature,
