ArticleMolecular therapy. Nucleic acids2019
Dual Mechanisms of Action of Self-Delivering, Anti-HIV-1 FANA Oligonucleotides as a Potential New Approach to HIV Therapy.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Decoding the Structural Complexity of Viral RNAs with SHAPE to Guide Antiviral Therapeutics.Viruses · 2026Review
- Beyond Antiretroviral Therapy: Molecular and Immunological Innovations in HIV Treatment.Tropical medicine and infectious disease · 2026Review
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- A modified X10-23 DNAzyme that can better access large, structured RNA targets.Nucleic acids research · 2026Article
- Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1.Frontiers in medicine · 2026Article
- Target, silence, replace: a review on RNA-based drugs in modern medicine.Frontiers in cell and developmental biology · 2026Review
- Article
- Endogenous Ribonucleases: Therapeutic Targeting of the Transcriptome Through Oligonucleotide-Triggered RNA Inactivation.Biomolecules · 2025Review
- Current State of Therapeutics for HTLV-1.Viruses · 2024Review
- Characterization of the SARS-CoV-2 Genome 3'-Untranslated Region Interactions with Host MicroRNAs.ACS omega · 2024Article
- Antisense targeting of FOXP3+ Tregs to boost anti-tumor immunity.Frontiers in immunology · 2024Article
- RNA-Based Vaccines and Therapeutics Against Intracellular Pathogens.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer.Respiratory research · 2023Article
- Antisense Therapy for Infectious Diseases.Cells · 2023Review
- Basic Principles of RNA Interference: Nucleic Acid Types and In Vitro Intracellular Delivery Methods.Micromachines · 2023Review
- The Expanded Central Dogma: Genome Resynthesis, Orthogonal Biosystems, Synthetic Genetics.Annual review of biophysics · 2023Review
- Small Molecule-Templated DNA Hydrogel with Record Stiffness Integrates and Releases DNA Nanostructures and Gene Silencing Nucleic Acids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Strategies for HIV-1 suppression through key genes and cell therapy.Frontiers in medicine · 2023Review
- TMEM123 a key player in immune surveillance of colorectal cancer.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Currently, the most effective and durable therapeutic option for HIV-1 infection is combination antiretroviral therapy (cART). Although cART is powerful and can delay viral evolution of drug resistance for decades, it is associated with limitations, including an inability to eradicate the virus and a potential for adverse effects. Therefore, it is imperative to discover new HIV therapeutic modalities. In this study, we designed, characterized, and evaluated the in vitro potency of 2'-deoxy-2'-fluoroarabinonucleotide (FANA) modified antisense oligonucleotides (ASOs) targeting highly conserved regions in the HIV-1 genome. Carrier-free cellular internalization of FANA ASOs resulted in strong suppression of HIV-1 replication in HIV-1-infected human primary cells. In vitro mechanistic studies suggested that the inhibitory effect of FANA ASOs can be attributed to RNase H1 activation and steric hindrance of dimerization. Using 5'-RACE PCR and sequencing analysis, we confirmed the presence of human RNase H1-mediated target RNA cleavage products in cells treated with FANA ASOs. We observed no overt cytotoxicity or immune responses upon FANA ASO treatment. Together, our results strongly suggest that FANA ASOs hold great promise for antiretroviral therapy. The dual ability of FANA ASOs to target RNA by recruiting RNase H1 and/or sterically blocking RNA dimerization further enhances their therapeutic potential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.