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Thermodynamics and kinetics guided probe design for uniformly sensitive and specific DNA hybridization without optimization.

ABSTRACT: Sensitive and specific DNA hybridization is essential for nucleic acid chemistry. Competitive composition of probe and blocker has been the most adopted probe design for its relatively high sensitivity and specificity. However, the sensitivity and specificity were inversely correlated over the length and concentration of the blocker strand, making the optimization process cumbersome. Herein, we construct a theoretical model for competitive DNA hybridization, which disclose that both the thermodynamics and kinetics contribute to the inverse correlation. Guided by this, we invent the 4-way Strand Exchange LEd Competitive DNA Testing (SELECT) system, which breaks up the inverse correlation. Using SELECT, we identified 16 hot-pot mutations in human genome under uniform conditions, without optimization at all. The specificities were all above 140. As a demonstration of the clinical practicability, we develop probe systems that detect mutations in human genomic DNA extracted from ovarian cancer patients with a detection limit of 0.1%.

SUBMITTER: Chen X

PROVIDER: S-EPMC6791858 | biostudies-other | 2019 Oct

REPOSITORIES: biostudies-other

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Thermodynamics and kinetics guided probe design for uniformly sensitive and specific DNA hybridization without optimization.

Chen Xin X Liu Na N Liu Liquan L Chen Wei W Chen Na N Lin Meng M Xu Jiaju J Zhou Xing X Wang Hongbo H Zhao Meiping M Xiao Xianjin X

Nature communications 20191014 1

Sensitive and specific DNA hybridization is essential for nucleic acid chemistry. Competitive composition of probe and blocker has been the most adopted probe design for its relatively high sensitivity and specificity. However, the sensitivity and specificity were inversely correlated over the length and concentration of the blocker strand, making the optimization process cumbersome. Herein, we construct a theoretical model for competitive DNA hybridization, which disclose that both the thermody ...[more]

PMID: 31611572

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Dataset Information

Thermodynamics and kinetics guided probe design for uniformly sensitive and specific DNA hybridization without optimization.

Publications

Thermodynamics and kinetics guided probe design for uniformly sensitive and specific DNA hybridization without optimization.

Similar Datasets

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