ArticleFrontiers in medicine2026
Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Dissection of the EIAV Core Packaging Region Identifies SL2 Stem and SL2-SL3 Junction as Gag-Associated Packaging Determinants and Antiviral Targets.International journal of molecular sciences · 2026Article
- Target, silence, replace: a review on RNA-based drugs in modern medicine.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
6 authors.
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Abstract
This study investigated the antiretroviral efficacy, toxicity profile, and cellular uptake of phosphothioate (PS) and PS/LNA-modified oligonucleotides within an in vitro HIV infection model. Phosphothioate (PS) oligonucleotides, designed to bind conserved regions of the HIV-1 genome, were modified at the 3' and/or 5' ends with LNA nucleotides. The antiviral properties of oligonucleotides against HIV-1 subtype A6 were evaluated using human MT-4 cell cultures. The antiretroviral activity of LNA-oligonucleotides against HIV-1 has been established. Variations in the 50% inhibitory viral reproductive dose (IC50) values among the oligonucleotides were observed, depending upon both the target and the incorporated LNA modification. Optimal IC50 values (90 ± 10 nM) were achieved using a PS oligonucleotide lacking LNA modifications, which targeted the HIV-1 integrase-encoding genomic region. Optimal HIV inhibitory action among LNA constructs was observed in an oligonucleotide with a 5'-end LNA modification targeting the HIV integrase region (IC50 = 1.12 ± 0.03 μM). The introduction of LNA modifications to PS oligonucleotides failed to enhance antiviral activity, as demonstrated by IC50 values revealing significant in vitro HIV-1 inhibitory capacity. The internalization of oligonucleotides demonstrating optimal IC50 values was investigated via flow cytometry and imaging techniques. Antisense oligonucleotides with single PS modification showed better antiretroviral activity with lower IC50 value compared to PS/LNA-modified antisense oligonucleotides. The reason for this difference is the better internalization ability of PS-modified oligonucleotides. The characteristic features included low toxicity (maintaining >92% viable cells after 48 h of culture), high cytoplasmic membrane sorption capacity (approximately 12% FAM + cells after 48 h), high penetration efficiency (approximately 98% FAM + cells showing cytoplasmic signal), and elevated internalization and entropy ratios.
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