アンチセンスDNAの細胞内分布に及ぼす要因

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Antisense DNA is promising therapeutic reagents based on specific inhibition of gene regulation. However, low membrane permeability is the major obstacle to deliver antisense DNA efficiently. To obtain the biological activity efficiently, antisense DNA should be delivered and bind to the target mRNA. Targeting efficacy of antisense DNA is critical issue from the pharmaceutical point of view. Since antisense DNA can block (1) transcription, (2) splicing, (3) maturation of mRNA, or (4) translocation, antisense DNA should be located in the nucleus. On the other hand, antisense DNA should be delivered in the cytoplasm to block the translation. Depends on the target site, antisense DNA should be located in the either cytoplasm or nucleus. To our knowledge, the factors are not still clear to alter the subcellular distribution of antisense DNA. To deliver antisense DNA to the proper target site, it is prerequisite to know transport mechanism of antisense DNA. We observed the subcellular distribution of antisense DNA under the confocal scanning microscope. And we tried to alter the subcellular distribution under the several conditions. Fluorescence labeled antisense DNA was punctately localized in the cytoplasm, little was in the nucleus. On the contrary, under the existence of lipofectin or virus, antisense DNA can be localized in the nucleus. Cytoplasmic pH was not great effect on the subcellular distribution of antisense DNA. From the results, it has feasibility to alter the subcellular distribution of antisense DNA, which could enhance the delivery efficacy.
日本DDS学会の論文
1995-03-10

アンチセンスDNAの細胞内分布に及ぼす要因

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