Anti-SV40 and anti-HIV-1 tat activity of natural and modified oligonucleotides

We have synthesized modified antisense sequences carrying l-2'-deoxynucleotides in the 5' and 3' termini. the effect of the oligonucleotides on SV40 replication was evaluatedon VERO cells measuring the production of viral DNA. the anti-HIV-1 activity was assesed on 293 cells contutively expressing tat and cat under the control of the HIV LTR. The extent of inhibition was related to the amount of acetylated cloramfenicol produced. In both cases L-2' deoxynucleotides resulted more active than their natural congeners, altought they were not devoted of cytotoxicity. The oligonucleotide cell uptake exibited the caracteristics of an active process i. e. temperature dependence and intracellular concentration much superior to the extracellular ones. Accumulation of L-oligomers was more than two fold higher than that of the natural derivatives, consistent with an increased resistence towards 3' and 5' exonucleases. Studies are in progress to verify if exonuclease resistance can be obtained by inserting L-2'-deoxynucleotides at internal positions.