Expanding the Design Rules for Discriminating Nucleic Acid Mutations via Mismatch-Exchange.

Authors

Yun Tan, Guan A Wang, Chenlan Shen, Yonggang Deng, Jie Zhang, Yue Wang, Yanjun Si, Dan Huang, Binwu Ying, Feng Li

Published in

Angewandte Chemie (International ed. in English). Pages e8342320. Jul 26, 2026. Epub Jul 26, 2026.

Abstract

Complementarity between nucleic acids via Watson-Crick base pairing formulates the basic principle for designing hybridization probes but often suffers low sequence selectivity against single nucleotide mutations. Herein, we report mismatch-exchange as a new design principle that allows the highly sensitive and robust discrimination of single nucleotide polymorphisms (SNPs) by simply manipulating the number and position of mismatches in both probes and the reaction products. Leveraging mismatches to drive the strand-exchange and finetuning the specificity, mismatch-exchange is particularly advantageous for analyzing complex nucleic acid targets containing multiple nearby SNPs. Both selective tolerance to synonymous SNPs and OR-gate-based detection of clustered drug-resistant SNPs were demonstrated. Once deployed to nucleic acid testing in clinical settings, mismatch-exchange enabled the discrimination of multiple lamivudine-resistant hepatitis B virus mutants in a clinical cohort containing 65 clinical plasma samples.

PMID:
42503210
Bibliographic data and abstract were imported from PubMed on 27 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.