チオール化アンチンス DNA の CH^RC5 細胞における取り込み機構と細胞内分布

概要

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One of the urgent matter to be concerned regarding with antisense DNA as therapeutic reagent is low membrane permeability. The dominant mechanism of cellular uptake of antisense DNA is thought to be endocytosis, although a recent publication indicated heterogeneous uptake of oligonucleotide. The event of oligonucleotide after the entering cells is still unclear. In this study we synthesized phosphorothioate oligonucleotide complementary to AUG initiation codon overlapping sequence of mRNA of mdrl and studied on charactersitic of cellular uptake in multiple drug resistant mutant of Chinese hamster ovary cells(CHRC5). Temperature dependent uptake suggested endocystosis as a uptake mechanism, Since non-labeled S-oligo inhibited cellular uptake of 32P labeled S-oligo in a dose dependent manner either at 4°C or 37°C, S-oligo seemed to have binding site on cellular membrane which was responsible for uptake. Rhodamin labeled S-oligo was distributed punctately for 2 hours or 24 hours with showing little portion in nucleus. After the treatment of monensin, H+/Na+ exchanger, cellular distribution pattern was changed. From this observation, part of S-oligo was seemed to distributed in lysosome.
日本DDS学会の論文