Inhibition of HIV-1 in vitro by C-5 propyne phosphorothioate antisense to rev.

A 15-mer C-5 propyne modified phosphorothioate oligodeoxynucleotide antisense to rev was approximately 5-fold more effective in providing viral inhibition compared to a 28-mer unmodified phosphorothioate oligodeoxynucleotide targeted to the same sequence and previously shown to inhibit HIV-1 in a sequence-dependent manner. The antiviral effect was obtained by lipofection or simple addition of 0.2-1 microM modified oligodeoxynucleotide to the culture medium of H9 cells chronically infected with the HIV-1LAI isolate of human immunodeficiency virus type 1. We conclude that C-5 propyne oligodeoxynucleotides in accordance with previous findings by others are superior to unmodified phosphorothioates in providing inhibition of HIV-1 in a sequence-dependent manner and that this inhibition can be conferred by oligodeoxynucleotides in free solution.