THE ROLE OF MULTIVALENT CATIONS IN OLIGONUCLEOTIDE CELLULAR UPTAKE

Oligodeoxynucleotides (ONs) are a powerful new class of drugs whose tr ansport to the cytoplasm or nucleus inefficient and incompletely defin ed. Thus, to further extend our understanding of the mechanism of ON c ellular uptake, the role of multivalent cations in ON cellular uptake was examined. All the multivalent cations tested, except magnesium, si gnificantly increase ON uptake and was predictably related to the cati on's electronegativity but only partially due to an increase in surfac e-binding. In addition, the primary mechanism of uptake is largely ind ependent of trypsin-sensitive surface components, cellular energy, and several specific, calcium-dependent cellular processes. Therefore, ON cellular uptake may involve an interaction between multivalent cation s and either the ON, the cell membrane, or both.