Growth inhibition of human leukemia HL-60 cells by an antisense phosphodiester oligonucleotide encapsulated into fusogenic liposomes.
We report here the antisense effect of phosphodiester oligodeoxynucleotide (D-ODN) using fusogenic liposomes (FL) as its carrier. FL has envelope proteins of the Sendai virus within its membrane and introduces its contents directly and efficiently into cytosol by means of the virus-cell fusion mechanism. Using antisense (AS) D-ODN 15-mer complementary to the c-myc proto-oncogene mRNA, including the translation initiation codon site, we analyzed the growth of HL-60 cells by [3H]-thymidine uptake. AS-ODNs encapsulated in FL inhibited the growth by about 70% that of the control HL-60 cells at 2.48 microM. In contrast, sense and scramble D-ODNs encapsulated in FL showed no effect of the growth of HL-60 cells at the same concentration. Even at 50 microM, free form D-ODNs did not show any effect. These results suggest that FL is potentially a useful delivery vehicle for oligonucleotide-based therapeutics, and that D-ODN may be a likely candidate for oligodeoxynucleotides when an efficient delivery system is used.
Kondoh
M
M
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Matsuyama
T
T
Suzuki
R
R
Mizuguchi
H
H
Nakanishi
T
T
Nakagawa
S
S
Tsutsumi
Y
Y
Nakanishi
M
M
Sato
M
M
Mayumi
T
T
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D016259:Genes, myc; D018922:HL-60 Cells; D006801:Humans; D008081:Liposomes; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas
D008081:Liposomes; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas