Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Growth Inhibition of Human Leukemia HL-60 Cells by an Antisense Phosphodiester Oligonucleotide Encapsulated into Fusogenic Liposomes
Masuo KONDOHTakahiro MATSUYAMARyo SUZUKIHiroyuki MIZUGUCHITsuyoshi NAKANISHIShinsaku NAKAGAWAYasuo TSUTSUMIMahito NAKANISHIMasao SATOTadanori MAYUMI
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2000 Volume 23 Issue 8 Pages 1011-1013

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Abstract

We report here the antisense effect of phosphodiester oligdoeoxynucleotide (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 μM. It 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 μM, 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.

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© The Pharmaceutical Society of Japan
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