Optical and theoretical study of strand recognition by nucleic acid probes

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...

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Detalles Bibliográficos
Autores: Ivana Domljanovic, Maria Taskova, Pâmella Miranda de Moura, Gerald Weber, Kira Astakhova
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:Brasil
Institución:Universidade Federal de Minas Gerais (UFMG)
Repositorio:Repositório Institucional da UFMG
Idioma:inglés
OAI Identifier:oai:repositorio.ufmg.br:1843/62264
Acceso en línea:https://doi.org/10.1038/s42004-020-00362-5
http://hdl.handle.net/1843/62264
https://orcid.org/0000-0002-9727-2496
https://orcid.org/0000-0001-8876-1864
https://orcid.org/0000-0002-2935-1571
https://orcid.org/0000-0003-4878-0301
Access Level:acceso abierto
Palabra clave:Optical and theoretical study
Nucleic acid probes
Biofísica
Ácidos nucleicos
Ótica
Descripción
Sumario: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.