Optical and Theoretical Study of Strand Recognition by Nucleic Acid Probes

Overview

Journal Commun Chem

Publisher Springer Nature

Specialty Chemistry

Date 2023 Jan 27

PMID 36703315

Authors

Ivana Domljanovic

Maria Taskova

Pamella Miranda

Gerald Weber

Kira Astakhova

Affiliations

Soon will be listed here.

Abstract

Detection of nucleic acids is crucial to the study of their basic properties and consequently to applying this knowledge to the determination of pathologies such as cancer. In this work, our goal is to determine new trends for creating diagnostic tools for cancer driver mutations. Herein, we study a library of natural and modified oligonucleotide duplexes by a combination of optical and theoretical methods. We report a profound effect of additives on the duplexes, including nucleic acids as an active crowder. Unpredictably and inconsistent with DNA+LNA/RNA duplexes, locked nucleic acids contribute poorly to mismatch discrimination in the DNA+LNA/DNA duplexes. We develop a theoretical framework that explains poor mismatch discrimination in KRAS oncogene. We implement our findings in a bead-bait genotyping assay to detect mutated human cancer RNA. The performance of rationally designed probes in this assay is superior to the LNA-primer polymerase chain reaction, and it agrees with sequencing data.

Citing Articles

Mutations in microRNA-128-2-3p identified with amplification-free hybridization assay.

Slott S, Kruger-Jensen C, Ferreira da Silva I, Bom Pedersen N, Astakhova K PLoS One. 2023; 18(8):e0289556.

PMID: 37607185 PMC: 10443835. DOI: 10.1371/journal.pone.0289556.

Natural and Modified Oligonucleotide Sequences Show Distinct Strand Displacement Kinetics and These Are Affected Further by Molecular Crowders.

Domljanovic I, Ianiro A, Ruegg C, Mayer M, Taskova M Biomolecules. 2022; 12(9).

PMID: 36139087 PMC: 9496266. DOI: 10.3390/biom12091249.

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