INHIBITION OF HIV-1 REPLICATION BY TRIPLE-HELIX-FORMING PHOSPHOROTHIOATE OLIGONUCLEOTIDES TARGETED TO THE POLYPURINE TRACT

We show the effects of triple-helix formation by assays of primer exte nsion inhibition ire vitro using two systems (two-strand-system (FTFOs ) or three-strand-system (TFOs)) targeted to the polypurine tract (PPT ) of HIV-1. The FTFOs were more effective thats the TFOs. We found tha t the FTFOs containing phosphorothioate groups at the 3'- and 5'-ends, of inside the hairpin loop, exhibited higher inhibitory effects on cD NA synthesis and greater exonuclease resistance than the unmodified FT FOs and TFOs. The abilities of the FTFOs containing phosphorothioate g roups at the antisense sequence sites to inhibit HIV-I replications we re examined. The FTFOs containing phosphorothioate. groups at the anti sense sequence sites inhibit the replication of HIV-1 more efficiently than the antisense oligonucleotides, indicating sequence-specific inh ibition of HIV-1 replication. (C) 1997 Academic Press.