GENE-TARGETED INHIBITION OF TRANSACTIVATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-LTR BY ANTISENSE OLIGONUCLEOTIDES

We have used an in vitro approach to study the efficiency of antisense oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression ca talyzed by tat protein, the functional protein of the transactivator g ene. We selected the target sequence localized near the 5' end of the tat mRNA. The following conclusions can be drawn from the data present ed here: a) Antisense oligonucleotides modified by conjugation of chol esterol at the 3' end have a severalfold higher inhibitory response, b ) inhibitory response is dependent on the mode of introducing oligonuc leotides, and c) the inhibition by antisense oligonucleotides is seque nce specific and directed towards the targeted region. This approach c ould be useful for targeting functional regions of regulatory gene pro ducts and designing gene-targeted inhibitors of virus replication.