Combining cooperativity with sequestration: a novel strategy for discrimination of single nucleotide variants

Hu, Shichao; Li, Na; Liu, Feng

doi:10.1039/c8cc00838h

Cited by 15 publications

(8 citation statements)

References 40 publications

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“…12,13 The need to achieve more costeffective, faster analysis and higher single nucleotide resolution continues to drive technological developments. 14 Recent examples include amendments to existing technologies such as molecular beacons, 15,16 melting analysis, 17,18 environmentally sensitive uorescent nucleobases, [19][20][21][22][23][24] and strand displacement probes 25,26 or new technologies such as polymerase-amplied release of ATP (POLARA) 27 or graphene-based biosensors for real-time kinetic monitoring of hybridization. 28 The analysis of SNVs requires technologies with the highest nucleotide resolution to ascertain the polymorphism or variation.…”

Section: Introductionmentioning

confidence: 99%

Enhanced SNP-sensing using DNA-templated reactions through confined hybridization of minimal substrates (CHOMS)

Kim

Winssinger

2020

Chem. Sci.

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Section: Introductionmentioning

confidence: 99%

Enhanced SNP-sensing using DNA-templated reactions through confined hybridization of minimal substrates (CHOMS)

Kim

Winssinger

2020

Chem. Sci.

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“…Even so, it was possible to easily differentiate DNA samples with 0, 1, or 2 mismatches when using a DNA concentration in the range of 300–600 nM, and a single C–C mismatched duplex could be detected at a concentration of 34 nM, while the LOD of a double C–C mismatch was 17 nM of DNA, or 34 nM of total C–C mismatches. While the limit of detection is poorer than competing SNP detection platforms (typically in the fM to pM range), the paper assay does have the ability to easily differentiate between normal DNA and that with a C–C mismatch so long as an appropriate concentration of DNA is applied to the test and has the advantage of being inexpensive, simple to use, and amenable to reading by eye. − …”

Section: Resultsmentioning

confidence: 99%

Enzymatic Litmus Test for Selective Colorimetric Detection of C–C Single Nucleotide Polymorphisms

2019

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A paper based litmus test has been developed using modulation of urease enzyme activity for detection of C–C mismatch single nucleotide polymorphisms (SNPs) by the naked eye. Urease is first inactivated with silver ions and printed onto paper microzones. Addition of DNA containing C–C mismatches reactivates urease via binding of Ag(I), allowing restoration of urease activity, hydrolysis of urea to produce ammonia, and an increase in pH, which is monitored colorimetrically using a pH indicator with a limit of detection of 11 nM DNA in 40 min. The assay system is easy to use, portable, and stable for at least 30 days at ambient temperature. To assess the versatility and practical application of the paper sensor, we used it to identify a G > C transversion present in human genomic DNA from a ductal carcinoma cell line, a mutation commonly found in breast cancer. We believe this new assay system has the potential to be a low-cost method for rapidly identifying DNA with the C–C mismatch SNP as a means of cancer screening in resource-limited areas.

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“…23,24 Enriching the toolbox of toeholdexchange probes with an alternative mechanism can improve the performance for single-nucleotide variant analysis. Presently, there are also several DNA probes with cooperative, dual-target response, 25,26 but these probes' specificity may be mainly due to the sequestration method or the kinetic obstacle. They often employed irreversible reaction design, so singlenucleotide variants can also trigger the probe's response due to favorable thermodynamics of toehold hybridization.…”

Section: ■ Introductionmentioning

confidence: 99%

Simulation-Guided Rational Design of DNA Probe for Accurate Discrimination of Single-Nucleotide Variants Based on “Hill-Type” Cooperativity

Hao

Yang

et al. 2023

Anal. Chem.

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The accurate discrimination of single-nucleotide variants is of great interest for disease diagnosis and clinical treatments. In this work, a unique DNA probe with “Hill-type” cooperativity was first developed based on toehold-mediated strand displacement processes. Under simulation, this probe owns great thermodynamics advantage for specificity due to two mismatch bubbles formed in the presence of single-nucleotide variants. Besides, the strategies of ΔG′ = 0 and more competitive strands are also beneficial to discriminate single-nucleotide variants. The feasibility of this probe was successfully demonstrated in consistent with simulation results. Due to “Hill-type” cooperativity, the probe allows a steeper dynamic range compared with previous probes. With simulation-guided rational design, the resulting probe can accurately discriminate single-nucleotide variants including nucleotide insertions, mutation, and deletions, which are arbitrarily distributed in target sequence. Two specificity parameters were calculated to quantitatively evaluate its good discrimination ability. Hence, “Hill-type” cooperativity can serve as a novel strategy in DNA probe’s design for accurate discrimination of single-nucleotide variants.

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Combining cooperativity with sequestration: a novel strategy for discrimination of single nucleotide variants

Cited by 15 publications

References 40 publications

Enhanced SNP-sensing using DNA-templated reactions through confined hybridization of minimal substrates (CHOMS)

Enhanced SNP-sensing using DNA-templated reactions through confined hybridization of minimal substrates (CHOMS)

Enzymatic Litmus Test for Selective Colorimetric Detection of C–C Single Nucleotide Polymorphisms

Simulation-Guided Rational Design of DNA Probe for Accurate Discrimination of Single-Nucleotide Variants Based on “Hill-Type” Cooperativity

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