2,6-diaminopurine (Z)-containing toehold probes improve genotyping sensitivity.

2,6-diaminopurine DNA synthesis genotyping toehold-mediated strand displacement

Journal

Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021

Informations de publication

Date de publication:
27 Dec 2023
Historique:
revised: 15 12 2023
received: 24 08 2023
accepted: 15 12 2023
medline: 28 12 2023
pubmed: 28 12 2023
entrez: 28 12 2023
Statut: aheadofprint

Résumé

2,6-diaminopurine (Z), a naturally occurring noncanonical nucleotide base found in bacteriophages, enhances DNA hybridization by forming three hydrogen bonds with thymine (T). These distinct biochemical characteristics make it particularly valuable in applications that rely on the thermodynamics of DNA hybridization. However, the practical use of Z-containing oligos is limited by their high production cost and the challenges associated with their synthesis. Here, we developed an efficient and cost-effective approach to synthesize Z-containing oligos of high quality based on an isothermal strand displacement reaction. These newly synthesized Z-oligos are then employed as toehold-blockers in an isothermal genotyping assay designed to detect rare single nucleotide variations (SNV). When compared with their counterparts containing the standard adenine (A) base, the Z-containing blockers significantly enhance the accuracy of identifying SNV. Overall, our innovative methodology in the synthesis of Z-containing oligos, which can also be used to incorporate other unconventional and unnatural bases into oligonucleotides, is anticipated to be adopted for diverse applications, including genotyping, biosensing, and gene therapy.

Identifiants

pubmed: 38151965
doi: 10.1002/bit.28642
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Natural Science Foundation of China (NSFC) Distinguished Young Scholar of China Program
ID : 32125002
Organisme : New Cornerstone Science Foundation
Organisme : National Key R&D Program of China
ID : 2019YFA0905700
Organisme : National Key R&D Program of China
ID : 2020YFA0712104

Informations de copyright

© 2023 Wiley Periodicals LLC.

Références

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Auteurs

Shaohua Kang (S)

School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China.

Qian Liu (Q)

School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China.

Jie Zhang (J)

School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China.

Yan Zhang (Y)

New Cornerstone Science Laboratory, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Hao Qi (H)

School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China.

Classifications MeSH