Single-step discovery of high-affinity RNA ligands by UltraSelex.

First Authors Yaqing Zhang
Authors Yaqing Zhang, Yuan Jiang, David Kuster, Qiwei Ye, Wenhao Huang, Simon Fürbacher, Jingye Zhang, Pia Doll, Wenjun Lin, Siwei Dong, Hui Wang, Zhipeng Tang, David Ibberson, Klemens Wild, Irmgard Sinning, Anthony Hyman, Andres Jäschke
Corresponding Authors Yaqing Zhang, Andres Jäschke
Last Authors Andres Jäschke
Journal Name Nature chemical biology (Nat Chem Biol)
Volume 21
Issue 7
Page Range 1118-1126
Open Access false
Print Publication Date 2025-07-01
Online Publication Date 2025-03-31
Abstract Aptamers, nucleic acid ligands targeting specific molecules, have emerged as drug candidates, sensors, imaging tools and nanotechnology building blocks. The predominant method for their discovery, systematic evolution of ligands by exponential enrichment, while successful, is laborious, time-consuming and often results in candidates enriched for unintended criteria. Here we present UltraSelex, a noniterative method that combines biochemical partitioning, high-throughput sequencing and computational signal-to-background rank modeling for discovering RNA aptamers in about 1 day. UltraSelex identified high-affinity RNA aptamers capable of binding a fluorogenic silicon rhodamine dye and two protein targets, the SARS-CoV-2 RNA-dependent RNA polymerase and HIV reverse transcriptase, enabling live-cell RNA imaging and efficient enzyme inhibition, respectively. From the ranked sequences, minimal aptamer motifs could be easily inferred. UltraSelex provides a rapid route to reveal new drug candidates and diagnostic tools.
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DOI 10.1038/s41589-025-01868-6
PubMed ID 40164941
WebOfScience Link WOS:001455389900001 (early)
Alternative Full Text URL https://www.researchsquare.com/article/rs-2713959/v1
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Created By thuem
Added Date 2025-04-09
Last Edited By thuem
Last Edited Date 2025-06-27 11:01:34.075
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