CELLULAR UPTAKE OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES AND THEIR ANALOGS

The uptake and intracellular distribution of oligonucleotide phosphoro thioates (S-oligonucleotides) and their analogs by various cells lines were studied using internally S-35-labeled oligonucleotides. Intracel lular accumulation starts in the first 2 hr and reaches a maximum at a bout 16 hr. A decrease of intracellular concentration of the S-oligonu cleotide was observed after 16 hr, probably due to a significant efflu x transport. Cellular uptake was dependent on the extracellular concen tration. The intracellular concentration was significantly higher than that in the medium. The uptake and the intracellular distribution wer e different in the various cell tines studied. Comparative studies of the uptake of the S-oligonucleotide and various 3' end-modified S-olig onucleotides show that end modified S-oligonucleotides with a hydropho bic group significantly increases the uptake. The introduction of meth ylphosphonothioate linkages at the 3' end of the S-oligonucleotide als o resulted in an increase in uptake.