ArticleNature chemistry2012
Optimizing the specificity of nucleic acid hybridization.
Article in Nature chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed.
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- FINDER converts zero-background kinetic fingerprinting into area-scalable attomolar biomarker detection.bioRxiv : the preprint server for biology · 2026Article
- Machine learning-directed massively parallel programmable nucleic acid amplification.Science advances · 2026Article
- Review
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- Compartmentalized Suspension Array for the Isothermal, Digital, and Multiplex Detection of microRNAs.Journal of the American Chemical Society · 2025Article
- Methods Established forPlants (Basel, Switzerland) · 2025Article
- Design of mismatch closure for enhanced specificity in DNA strand displacement reactions.Nucleic acids research · 2025Article
- Chromato-Kinetic Fingerprinting Enables Multiomic Digital Counting of Single Disease Biomarker Molecules.ACS nano · 2025Article
- A bibliometric analysis of nucleic acid probe and its applications in oncology: towards more precise molecular medicine.Discover oncology · 2025Review
- Nonequilibrium hybridization-driven CRISPR/Cas adapter with extended energetic penalty for discrimination of single-nucleotide variants.Nucleic acids research · 2025Article
- Reaction Pathway Differentiation Enabled Fingerprinting Signal for Single Nucleotide Variant Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chromato-kinetic fingerprinting enables multiomic digital counting of single disease biomarker molecules.bioRxiv : the preprint server for biology · 2025Article
- Massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS).Nature communications · 2025Article
- ThermoPlex: an automated design tool for target-specific multiplex PCR primers based on DNA thermodynamics.Biology methods & protocols · 2025Article
- Ultrasensitive Amplification-Free Quantification of a Methyl CpG-Rich Cancer Biomarker by Single-Molecule Kinetic Fingerprinting.Analytical chemistry · 2024Article
80 more citing papers are in PubMed but not listed here.
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3 authors.
Funding
Abstract
The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed 'toehold exchange' probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg(2+) to 47 mM Mg(2+), and with nucleic acid concentrations from 1 nM to 5 µM. Experiments with RNA also showed effective single-base change discrimination.
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