Scientific article
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English

Sequencing of D/L -DNA and XNA by Templated-Synthesis

Published inJournal of the American Chemical Society, vol. 147, no. 7, p. 6288-6296
Publication date2025-02-19
First online date2025-02-11
Abstract

Progress in oligonucleotide sequencing has transformed modern biology and medicine. Here we report a fast and efficient enzyme-free primer extension of PNA with reversible chain termination and its application to DNA and XNA sequencing. The approach leverages activated 4-mer PNAs that react in a templated ligation reaction at μM concentrations within minutes. We demonstrate that the fidelity of this enzyme-free primer extension benefits from reactions performed with a mixture of activated PNAs where every 4-mer has its self-complementary 4-mer. The reactions can be performed using the whole repertoire of 4-mers (256 permutations) in a parallelized manner. Using a primer in combination with its -1, -2, and -3 deletion allows for sequencing by MALDI analysis, using the increment in mass for each nucleobase assignment. Given the enzyme-free nature of this sequencing and the achiral nature of PNA, we further demonstrate that the technology can be used to sequence d- or l-DNA as well as LNA and PNA (XNA).

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Citation (ISO format)
JOSHI, Saurabh, ROMANENS, Patrick, WINSSINGER, Nicolas. Sequencing of D/L -DNA and XNA by Templated-Synthesis. In: Journal of the American Chemical Society, 2025, vol. 147, n° 7, p. 6288–6296. doi: 10.1021/jacs.5c00708
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Additional URL for this publicationhttps://pubs.acs.org/doi/10.1021/jacs.5c00708
Journal ISSN0002-7863
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