A PHOSPHOROTHIOATE OLIGONUCLEOTIDE BLOCKS REVERSE TRANSCRIPTION VIA AN ANTISENSE MECHANISM

We have studied the inhibition by a phosphorothioate oligodeoxynucleot ide (17PScap) of cDNA synthesis performed by either avian or murine re verse transcriptase, Three different mechanisms of inhibition were ide ntified: at low concentrations (<100 nM), the cleavage of the RNA temp late by the retroviral RNase H at the level of the RNA/17PScap duplex accounted for most of the effect, whereas hybrid-arrested cDNA synthes is by an RNase H-independent mechanism marginally contributed to the i nhibition. Both mechanisms were sequence-specific. Above 100 nM, the o verall cDNA synthesis was reduced in a non-specific manner.