ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2023
Success probability of high-affinity DNA aptamer generation by genetic alphabet expansion.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Aptamer-Functionalized Nanocarriers for Bone and Joint Diseases: Engineering Design Rules and Translational Roadmap.Small science · 2026Article
- High-Affinity Six-Letter DNA XenoAptamer Generation by Genetic Alphabet Expansion.Journal of the American Chemical Society · 2026Article
- Expanded genetic alphabet increases structural and chemical diversity of six-letter DNA for high-affinity protein-targeting aptamers.Nature communications · 2025Article
- Adaptation of a Model Spike Aptamer for Isothermal Amplification-Based Sensing.Sensors (Basel, Switzerland) · 2024Article
- Strict Interactions of Fifth Letters, Hydrophobic Unnatural Bases, in XenoAptamers with Target Proteins.Journal of the American Chemical Society · 2023Article
- Success probability of high-affinity DNA aptamer generation by genetic alphabet expansion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Reactivity and mechanism in chemical and synthetic biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Chemically modified aptamers for improving binding affinity to the target proteinsFrontiers in cell and developmental biology · 2023Review
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Authors and funding
5 authors at 1 institution in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleic acid aptamers as antibody alternatives bind specifically to target molecules. These aptamers are generated by isolating candidates from libraries with random sequence fragments, through an evolutionary engineering system. We recently reported a high-affinity DNA aptamer generation method that introduces unnatural bases (UBs) as a fifth letter into the library, by genetic alphabet expansion. By incorporating hydrophobic UBs, the affinities of DNA aptamers to target proteins are increased over 100-fold, as compared with those of conventional aptamers with only the natural four letters. However, there is still plenty of room for improvement of the methods for routinely generating high-affinity UB-containing DNA (UB-DNA) aptamers. The success probabilities of the high-affinity aptamer generation depend on the existence of the aptamer candidate sequences in the initial library. We estimated the success probabilities by analysing several UB-DNA aptamers that we generated, as examples. In addition, we investigated the possible improvement of conventional aptamer affinities by introducing one UB at specific positions. Our data revealed that UB-DNA aptamers adopt specific tertiary structures, in which many bases including UBs interact with target proteins for high affinity, suggesting the importance of the UB-DNA library design. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.
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