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Expanding detection windows for discriminating single nucleotide variants using rationally designed DNA equalizer probes
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Expanding detection windows for discriminating single nucleotide variants using rationally designed DNA equalizer probes
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Journal Article
Expanding detection windows for discriminating single nucleotide variants using rationally designed DNA equalizer probes
2020
Overview
Combining experimental and simulation strategies to facilitate the design and operation of nucleic acid hybridization probes are highly important to both fundamental DNA nanotechnology and diverse biological/biomedical applications. Herein, we introduce a DNA equalizer gate (DEG) approach, a class of simulation-guided nucleic acid hybridization probes that drastically expand detection windows for discriminating single nucleotide variants in double-stranded DNA (dsDNA) via the user-definable transformation of the quantitative relationship between the detection signal and target concentrations. A thermodynamic-driven theoretical model was also developed, which quantitatively simulates and predicts the performance of DEG. The effectiveness of DEG for expanding detection windows and improving sequence selectivity was demonstrated both in silico and experimentally. As DEG acts directly on dsDNA, it is readily adaptable to nucleic acid amplification techniques, such as polymerase chain reaction (PCR). The practical usefulness of DEG was demonstrated through the simultaneous detection of infections and the screening of drug-resistance in clinical parasitic worm samples collected from rural areas of Honduras.
The design of nucleic acid hybridisation probes is important for their use in DNA nanotechnology and biomedical applications. Here the authors use a DNA equalizer gate approach that expands the detection windows for improved sequence selectivity.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
