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Updated: May 21, 2025

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In Vitro Selection of Aptamers to Differentiate Infectious from Non-Infectious Viruses
Published on: September 7, 2022
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DNA Aptamers with Chemically Locked Ends for Virus Infection Inhibition
Wenzhe Song1, Chuanxi Li2,3, Yuhang Dong1
1State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, 100029, China.
ACS Applied Materials & Interfaces
|March 21, 2025
Summary
Nucleic acid aptamers can be stabilized against degradation using chemical cross-linking of terminal bases. This method enhances aptamer stability and function, showing promise for clinical applications like inhibiting SARS-CoV-2 infection.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Development
Background:
- Nucleic acid aptamers offer high affinity and specificity, serving as alternatives to antibodies.
- A major limitation of aptamers is their susceptibility to nuclease degradation, hindering biological applications.
Purpose of the Study:
- To develop a method for enhancing aptamer stability and nuclease resistance.
- To investigate the efficacy of small-molecule-mediated terminal manipulation for aptamer stabilization.
Main Methods:
- Designing aptamers with terminal T-T bases for chemical cross-linking with trioxsalen.
- Synthesizing aptamers with varying terminal T-T cross-linking patterns.
- Employing experimental investigations and molecular dynamics simulations to assess cross-linking efficiency and aptamer stability.
- Evaluating the performance of terminal-locked aptamers in inhibiting SARS-CoV-2 infection.
Main Results:
- Cross-linking efficiency depends on the number of T-T sites, aptamer conformation, and competitive binding.
- Aptamers with locked 3' and 5' ends showed significantly improved exonuclease resistance and target binding.
- Terminal-locked aptamers demonstrated superior performance in inhibiting SARS-CoV-2 infection by targeting viral receptor-binding domains.
Conclusions:
- Small-molecule-mediated terminal manipulation provides a robust strategy for stabilizing DNA aptamers.
- This approach enhances aptamer resistance to nucleases and preserves target binding capabilities.
- The developed method holds significant potential for advancing the clinical applications of nucleic acid-based therapeutics.
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