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Updated: Oct 22, 2025
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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
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Structure-based design of antisense oligonucleotides that inhibit SARS-CoV-2 replication
Yan Li1,2, Gustavo Garcia3, Vaithilingaraja Arumugaswami3,4
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, U.S.A.
Biorxiv : the Preprint Server for Biology
|August 31, 2021
Summary
New 3D-ASOs target SARS-CoV-2 RNA structures, enhancing drug design. This structure-based approach improves antisense oligonucleotide (ASO) therapy for viral infections and beyond.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Antisense oligonucleotides (ASOs) are RNA-targeting drugs.
- Current ASO design relies on Watson-Crick base pairing.
- RNA secondary structures can impede ASO binding and efficacy.
Approach:
- Developed a structure-based ASO design method using 3D structural templates.
- Engineered 3D-ASOs to interact with target RNA structures via tertiary interactions.
- Applied the method to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Key Points:
- 3D-ASOs achieve enhanced affinity and specificity by recognizing RNA shape and hydrogen bonding patterns.
- Designed 3D-ASOs targeting the SARS-CoV-2 frameshift stimulation element and transcription regulatory sequence.
- Identified lead 3D-ASOs that potently inhibit viral replication in human cells.
Conclusions:
- Optimized lead 3D-ASO sequences and characterized structure-activity relationships.
- Demonstrated the potential of 3D-ASO technology to combat COVID-19.
- Highlighted the broad applicability of this novel ASO design strategy for future drug development.
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