Cellular uptake of antisense oligonucleotides is critical to their abi
lity to inhibit gene expression. In the present study, phosphodiester
oligodeoxynucleotides were introduced into cells during brief permeabi
lization with the pore-forming agent streptolysin O. The extent of ant
isense inhibition was dependent on the concentration of oligonucleotid
e present during permabilization. In addition, the level of antisense
inhibition was time-dependent; it reached a maximum at 18 h and subseq
uently diminished to control levels over the next 48 h. These results
demonstrate the effectiveness of streptolysin O permeabilization as a
means for simple and rapid introduction of oligonucleotides into eukar
yotic cells.