INFLUENCE OF BASE COMPOSITION ON MEMBRANE-BINDING AND CELLULAR UPTAKEOF 10-MER PHOSPHOROTHIOATE OLIGONUCLEOTIDES IN CHINESE-HAMSTER OVARY (CH(R)C5) CELLS

A key problem in antisense therapeutics is the relatively poor cell up take of oligonucleotides and subsequent transport to the cytoplasm and nucleus. Although the chemical characteristics of oligonucleotides se em likely to affect their uptake by cells, little is known about this issue. In this article we explore the effect of base composition on ol igonucleotide uptake. We show that phosphorothioate homo-G oligomers h ave a distinctly greater cellular uptake than other phosphorothioate h omooligomers. This is probably due to a greater initial association wi th the plasma membrane, because homo-G oligomers show the greatest bin ding to, liposome membranes, when tested at physiological ionic streng th. Under different buffer conditions appreciable differences in membr ane binding to liposomes were detected for the various homooligonucleo tides.