1. Academic Validation
  2. Selective targeting of parallel G-quadruplex structure using L-RNA aptamer

Selective targeting of parallel G-quadruplex structure using L-RNA aptamer

  • Nucleic Acids Res. 2023 Oct 23:gkad900. doi: 10.1093/nar/gkad900.
Danyang Ji 1 Jia-Hao Yuan 2 Shuo-Bin Chen 2 Jia-Heng Tan 2 Chun Kit Kwok 1 3
Affiliations

Affiliations

  • 1 Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China.
  • 2 Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 3 Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China.
Abstract

G-quadruplexes (G4) are special nucleic acid structures with diverse conformational polymorphisms. Selective targeting of G-quadruplex conformations and regulating their biological functions provide promising therapeutic intervention. Despite the large repertoire of G4-binding tools, only a limited number of them can specifically target a particular G4 conformation. Here, we introduce a novel method, G4-SELEX-Seq and report the development of the first L-RNA aptamer, L-Apt12-6, with high binding selectivity to parallel G4 over Other nucleic acid structures. Using parallel dG4 c-Kit 1 as an example, we demonstrate the strong binding affinity between L-Apt12-6 and c-Kit 1 dG4 in vitro and in cells, and notably report the applications of L-Apt12-6 in controlling DNA replication and gene expression. Our results suggest that L-Apt12-6 is a valuable tool for targeting parallel G-quadruplex conformation and regulating G4-mediated biological processes. Furthermore, G4-SELEX-Seq can be used as a general platform for G4-targeting L-RNA Aptamers selection and should be applicable to Other nucleic acid structures.

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