G4-SLSELEX-Seq-driven discovery of a G4-specific targeting L-RNA aptamer with unique structural features

Tian-Ying Wu; Chun Kit Kwok

doi:10.1039/d5ob00526d

G4-SLSELEX-Seq-driven discovery of a G4-specific targeting L-RNA aptamer with unique structural features

Tian-Ying Wu, Chun Kit Kwok^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

1 Citation (Scopus)

Abstract

We integrated sequence-guided library design into G4-SLSELEX-Seq, expanding its application to aptamer selection against DNA G-quadruplexes (dG4s). This strategy identified L-Apt.G3, the first L-RNA aptamer exhibiting low nanomolar binding affinity and dual-specificity binding to parallel and antiparallel G4s through a unique binding motif. Additionally, L-Apt.G3 can competitively disrupt dG4-protein interactions. © 2025 The Royal Society of Chemistry.

Original language	English
Pages (from-to)	9851-9856
Number of pages	6
Journal	Organic & Biomolecular Chemistry
Volume	23
Issue number	43
Online published	2 Jul 2025
DOIs	https://doi.org/10.1039/d5ob00526d
Publication status	Published - 21 Nov 2025

Funding

This work is supported by National Natural Science Foundation of China Projects [32471343, 32222089]; Research Grants Council of the Hong Kong SAR, China, Projects (RFS2425-1S02, CityU 11100123, CityU 11100222, CityU 11100421); Croucher Foundation Project (9509003); State Key Laboratory of Marine Pollution (SCRF/0070); and City University of Hong Kong Projects (9680376, 7030001, 9678302) to C. K. K.

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abstract = "We integrated sequence-guided library design into G4-SLSELEX-Seq, expanding its application to aptamer selection against DNA G-quadruplexes (dG4s). This strategy identified L-Apt.G3, the first L-RNA aptamer exhibiting low nanomolar binding affinity and dual-specificity binding to parallel and antiparallel G4s through a unique binding motif. Additionally, L-Apt.G3 can competitively disrupt dG4-protein interactions. {\textcopyright} 2025 The Royal Society of Chemistry.",

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AU - Kwok, Chun Kit

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AB - We integrated sequence-guided library design into G4-SLSELEX-Seq, expanding its application to aptamer selection against DNA G-quadruplexes (dG4s). This strategy identified L-Apt.G3, the first L-RNA aptamer exhibiting low nanomolar binding affinity and dual-specificity binding to parallel and antiparallel G4s through a unique binding motif. Additionally, L-Apt.G3 can competitively disrupt dG4-protein interactions. © 2025 The Royal Society of Chemistry.

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DO - 10.1039/d5ob00526d

M3 - RGC 21 - Publication in refereed journal

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JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

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ER -

G4-SLSELEX-Seq-driven discovery of a G4-specific targeting L-RNA aptamer with unique structural features

Abstract

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RFS: Developing RNA Structure-Targeting Bi-/Multi-Functional Laptamer-Based Chimeras for Gene Regulation

GRF: Developing Novel Short Peptides to Target G-quadruplex Structure and Modulate Gene Function

GRF: Evolving New L-RNA Aptamers and Developing L-RNA aptamer-peptide Conjugates to Control G-quadruplex Structure-associated Gene Activity

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