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Quantifying metabolites using structure-switching aptamers coupled to DNA sequencing

June H. Tan, Andrew Fraser

2025Nature Biotechnology14 citationsDOIOpen Access PDF

Abstract

Here we report a method, smol-seq (small-molecule sequencing), using structure-switching aptamers (SSAs) and DNA sequencing to quantify metabolites. In smol-seq, each SSA detects a single target molecule and releases a unique DNA barcode on target binding. Sequencing the released barcodes can, thus, read out metabolite levels. We show that SSAs are highly specific and can be multiplexed to detect multiple targets in parallel, bringing the power of DNA sequencing to metabolomics.

Topics & Concepts

AptamerComputational biologyDNA sequencingDNABiologyGeneticsAdvanced biosensing and bioanalysis techniquesRNA and protein synthesis mechanismsDNA and Nucleic Acid Chemistry
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