biostudies-literatureLau HLResearch Grants Council of the Hong Kong SAR, China ProjectsNSFC Excellent Young Scientists Fund ProjectState Key Laboratory of Marine Pollution Seed Collaborative Research FundCity University of Hong Kong projectsCroucher Foundatione2401097https://www.ebi.ac.uk/biostudies/studies/S-EPMC11926469biostudies-literatureUnknown9(3)RNA G-quadruplex structures (rG4s) play important roles in the regulation of biological processes. So far, all the l-RNA aptamers developed to target rG4 of interest contain G4 motif itself, raising the question of whether non-G4-containing l-RNA aptamer can be developed to target rG4. Furthermore, it is unclear whether an l-Aptamer-based tool can be generated for G4 detection in vitro and imaging in cells. Herein, a new strategy is designed using a low GC content template library to develop a novel non-G4-containing l-RNA aptamer with strong binding affinity and improved binding specificity to rG4 of interest. The first non-G4-containing l-Aptamer, l-Apt.1-1, is identified with nanomolar binding affinity to amyloid precursor protein (APP) D-rG4. l-Apt.1-1 is applied to control APP gene exSmall methodsSpecific Targeting and Imaging of RNA G-Quadruplex (rG4) Structure Using Non-G4-Containing l-RNA Aptamer and Fluorogenic l-Aptamer.PMC11926469CityU11100123CityU11100222SCRF/003732222089CityU111004216000827RFS2425-1S02SCRF/0070SCRF/0040967830295090037030001Kwok CKFeng HLau HLZhao HfalseSpecific Targeting and Imaging of RNA G-Quadruplex (rG4) Structure Using Non-G4-Containing l-RNA Aptamer and Fluorogenic l-Aptamer.RNA G-quadruplex structures (rG4s) play important roles in the regulation of biological processes. So far, all the l-RNA aptamers developed to target rG4 of interest contain G4 motif itself, raising the question of whether non-G4-containing l-RNA aptamer can be developed to target rG4. Furthermore, it is unclear whether an l-Aptamer-based tool can be generated for G4 detection in vitro and imaging in cells. Herein, a new strategy is designed using a low GC content template library to develop a novel non-G4-containing l-RNA aptamer with strong binding affinity and improved binding specificity to rG4 of interest. The first non-G4-containing l-Aptamer, l-Apt.1-1, is identified with nanomolar binding affinity to amyloid precursor protein (APP) D-rG4. l-Apt.1-1 is applied to control APP gene ex2025-01-01T00:00:00Z2025 Mar2025-04-20T00:14:20.412Z2025-04-20T00:14:20.412ZS-EPMC119264693922491110.1002/smtd.202401097