ArticleMolecular therapy. Nucleic acids2024
Mechanistic insights into ASO-RNA complexation: Advancing antisense oligonucleotide design strategies.
Article in Molecular therapy. Nucleic acids, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Antisense Versus Antigene in the Computer-Aided Design of Triplex-Forming Oligonucleotides (TFO): Insights from a Dual-Method Review, Combining Bibliometric and Systematic Review.International journal of molecular sciences · 2025Pooled it
- Silencing with precision: In silico strategies for antisense oligonucleotide engineering.Molecular biology reports · 2026Review
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Artificial intelligence in biologic drug discovery: A review of methodological evolution and therapeutic applications.Acta pharmaceutica Sinica. B · 2026Review
- ClinASO: An open-source platform for rapid drug discovery of gapmer antisense oligonucleotides.Molecular therapy. Nucleic acids · 2026Article
- ETS‑1/ETS‑2 transcription factors in CVD (Review).International journal of molecular medicine · 2026Review
- The role of long non-coding RNAs in therapy resistance of cervical cancer and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Chemically inducible antisense oligonucleotides for cell-specific gene silencing.RSC chemical biology · 2025Article
- Small nucleic acid drugs-the dawn of functional cure of chronic hepatitis B.Frontiers in pharmacology · 2025Review
- Exosomes and Renal Fibrosis: Diagnostic Value, Therapeutic Potential and Challenges.International journal of nanomedicine · 2025Review
- ETS-1 in tumor immunology: implications for novel anti-cancer strategies.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligonucleotide drugs, an emerging modulator class, hold promise for targeting previously undruggable biomacromolecules. To date, only 18 oligonucleotide drugs, including sought-after antisense oligonucleotides (ASOs) and splice-switching oligonucleotides, have approval from the U.S. Food and Drug Administration. These agents effectively bind mRNA, inducing degradation or modulating splicing. Current oligonucleotide drug design strategies prioritize full Watson-Crick base pair (bp) complementarity, overlooking mRNA target three-dimensional shapes. Given that mRNA conformational diversity can impact hybridization, incorporating mRNA key structural properties into the design may expedite ASO lead discovery. Using atomistic molecular dynamics simulations inspired by experimental data, we demonstrate the advantages of incorporating common triple bps into the design of ASOs targeting RNA hairpin motifs, which are highly accessible regions for interactions. By using an RNA pseudoknot modified into an ASO-hairpin complex, we investigate the effects of ASO length and hairpin loop mutations. Our findings suggest that ASO-mRNA complex stability is influenced by ASO length, number of common triple bps, and the dynamic accessibility of bases in the hairpin loop. Our study offers new mechanistic insights into ASO-mRNA complexation and underscores the value of pseudoknots in constructing training datasets for machine learning models aimed at designing novel ASO leads.
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Registered trials
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