VEGFmRNAに対するアンチセンスDNAのヒト臍帯静脈細胞の管腔形成制御効果をカチオン性リポソームが増強

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In the past decade, many researchers have been keen to apply the antisense oligonucleotides as therapeutic agents. Several antisense molecules are now going on the clinical trials. However, unappropriated targeting efficacy hamper to get suffifcient biological activities. The effort to overcome the nuclease instability of antisense molecules leads to developement of various stable analogues. Since antisense molecules distribute in lysosomes, sufficient biological functions can not be expected. If antisnese molecules can be delivered to appropriate site with high efficiency, application of antisense strategy would be widened. In this study, we synthesized antisense phosphorothioate oligonucleotides (S-oligo) toward mRNA of vascular endothelial growth factor (VEGF) and 80 S-oligos candidates were tested in <I>in vitro</I> translation system. From this selection, 4 compounds were tested as the inhibitory effect on tube formation of human umbilical vascular endothelial cell (HUVEC). Since inhibitory effect of S-oligo on bute formation of HUVEC was not sufficient enough, we used transfectam to enhance the biological activity of S-oligo. Transfectam enhanced the inhibitory activity of S-oligo. While S-oligo itself were distributed in the cytoplasm punctately, S-oligo and transfectam complex localized in the cytoplasm and some fractions were in the nucleus. Localization of S-oligo in whole cells would contribute to enhance the biological activity. However, further study is required to obtain the enhancement of particular antisense activity in a sequence specific manner.
日本DDS学会の論文
1997-05-10

VEGFmRNAに対するアンチセンスDNAのヒト臍帯静脈細胞の管腔形成制御効果をカチオン性リポソームが増強

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