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We have developed a photo-cross-linked oligonucleotide (clip-ODN) for a novel type of gene regulator molecule. Here, we examined the ability of the clip-ODN as a decoy DNA on regulation of the transcriptional activity of estrogen receptor (ER). A photo-cross-linking reagent, 4,5',8-[4'-(aminoethyl-amino) methyl]-trimethylpsoralen (aeAMT) was conjugated with an ODN at the 5'-end, and the aeAMT was cross-linked with the thymine residue of the complementary oligonucleotide upon UVA irradiation (365nm). The clip-ODN drastically inhibited the proliferation of breast cancer cell line (MCF-7) than non-cliped one in a sequence specific manner. This finding revealed that photo-cross-linking of double stranded ODN improve the regulatory ability as a decoy DNA, and clip-ODN may be a valuable tool in gene therapy protocols for inhibiting breast cancer cells' proliferation.

Gene regulation by decoy approach (II): Development of photo-cross-linked oligonucleotides duplex as a decoy DNA for estrogen receptor