PMID: 8449923Mar 15, 1993Paper

Characterization of the nuclear binding sites of oligodeoxyribonucleotides and their analogs.

The Journal of Biological Chemistry
J P ClarencJ P Léonetti

Abstract

The intracellular fate of antisense oligodeoxyribonucleotide (oligomers) is poorly understood. Recent observations strongly suggest that after endocytosis and escape from the endocytic compartments, oligomers accumulate in the nuclei of eukaryotic cells by simple diffusion. Isolated nuclei were used to determine the number of these nuclear binding sites and their affinity for phosphodiester, phosphorothioate, and methyl-phosphonate oligomers. These cell-free assays were correlated with intact cell microinjection experiments. Great differences have been observed between these analogs. These data are helpful in understanding the fate of oligomers and the mechanism of their action and could be helpful for a more rational design of antisense molecules.

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