Antiviral activity of antisense oligonucleotide combinations targeting various regions of the HIV‐1 genome

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Abstract
The goal of this study was to investigate the effectiveness in suppressing viral replication of combinations of antisense phosphorothioate oligodeoxyribonucleotides targeting conserved regions in the HIV‐1 genome. The antiretroviral activity of the antisense oligonucleotides was evaluated using human MT4 lymphocyte culture infected with HIV‐1 subtype A6. The amount of viral protein p24 was measured using an enzyme immunoassay (ELISA) to determine the effectiveness of the oligonucleotides treatments.The oligonucleotides studied and their combinations showed the ability to inhibit HIV‐1 replication at nanomolar concentrations. Among the mono‐oligonucleotides, the one targeting the gag gene region had the best anti‐viral suppression (IC50 = 58 ± 4.4 nM). Among the combinations, the most effective (IC50 = 29 ± 1.7 nM) consisted of oligonucleotides targeting the gag region and the primer binding site. These results confirm the potential of combining oligonucleotides that target different regions of the HIV‐1 genome to synergistically increase the anti‐viral effect, as compared to using each oligonucleotide individually. The justification for using a combination of oligonucleotides is important because the multidirectional antiviral effect of these molecules minimises the potential negative impact of HIV's mutational variability on the effectiveness of antiviral drugs.

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