RNA G-quadruplex structure targeting and imaging: recent advances and future directions

TABLE 2.

Summary of current rG4 structure imaging studies

Name Target rG4 Ex. Em. Biophysical approaches Biological system Applications References
Small molecules
QUMA-1 rG4s in cells 555 660 Fluorescence spectroscopy, competition assay, CD, NMR, HPLC, MS Cell line: HeLa General rG4 dynamic Chen et al. 2018b
ThT-NE HCV RNA CG2a 461 495 Fluorescence spectroscopy: 1693-fold in vitro, CD, UV-Vis spectroscopy, gel electrophoresis, NMR Cell line: Huh7, FCA1, GG2, GG2-G4Mut and HLCZ01 Hepatitis C virus (HCV) infection Luo et al. 2019
NIR-2 HCV RNA CG2a 591 689 Fluorescence spectroscopy, CD, NMR, HRMS Cell line: Huh7, FCA1, GG2-G4-Mut and GG2
Organ: Huh7 or GG2 cell xenograft mice 3.4-fold ex vivo
HCV infection Zhang et al. 2021
ThT-NA rG4s in cells 510 610 Fluorescence spectroscopy, CD, NMR Cell line: HepG2 and HeLa
Tissue: HeLa cell xenograft mice
Cancer Lu et al. 2022
TCB-1 Abnormal NOP56 RNA 490 526 Fluorescence spectroscopy: 150 to 438-fold with dG4/rG4 in vitro, UV-Vis spectroscopy, NMR, MS Cell line: HeLa and MCF-7, 8-Fold Autosomal dominant spinocerebellar ataxia 36 (SCA36) Sun et al. 2023
TOR-G4 rG4s in cells 467 540 Fluorescence spectroscopy, UV-Vis spectroscopy, NMR, MS Cell line: U2OS Fluorescent lifetime-based imaging Robinson et al. 2024
NIRG-2 dG4s and rG4s 850 940 Fluorescence spectroscopy, CD, NMR Cell line: 4T1, HEK293, A549, MCF-7, LX-2, and L929
Tissue: chicken breast
Tumor: 4T1 subcutaneous xenograft mice: 47-fold in vivo
Cancer lymphatic metastasis Wang et al. 2024
SCY-5 Parallel dG4s and rG4s 575 / Fluorescence spectroscopy, UV-vis spectroscopy, native gel electrophoresis, NMR Cell line: HUVECs, MCF-10A, MCF-7, HeLa, A549, and SMMC7721, >3.5-fold in tumor cells, twofold in normal cells
Blood: greater than twofold for cancer patient, twofold for normal patient
Cancer Sun et al. 2024
4S-2TO-4a dG4s and rG4s 498 680 Fluorescence spectroscopy, CD, UV-Vis spectroscopy, native gel electrophoresis, NMR, HRMS Cell line: HeLa General G4 imaging Parveen et al. 2024
ThT dG4s and rG4s 404 490 Fluorescence spectroscopy, TCSPC time-resolved decays, UV-Vis spectroscopy, Cell line: U2OS General G4 imaging Bradford et al. 2024
TzN-TASQ dG4s and rG4s 286 414 Fluorescence spectroscopy, UV-Vis spectroscopy, NMR, molecular dynamics simulations General G4 detection Ledvinka et al. 2024
Small molecule + antibody
5-BrdU PDC + antibody rG4s in cells / 450 G4-FID, click reaction Cell line: A549 and A2780 General G4 imaging Masson et al. 2021
Small molecule + antisense
ISCH-app APP rG4 570 650 Fluorescence spectroscopy, CD, UV-Vis spectroscopy, RTS assay, SHALiPE assays Cell line: HEK293T and HeLa, 28–50-fold in cells Alzheimer's Disease (AD) Lyu et al. 2019
MAMPA BCL2 rG4 488 520 Fluorescence spectroscopy, MS Cell line: HeLa, MCF 10A, MDA-kb2, MCF-7, BT-474, SK-BR3, MDA-MB-231, mESC, and 293FT Proto-oncogene Dai et al. 2022
Aptamer
L-Apt.1-1_Pepper APP rG4 485 530 Fluorescence spectroscopy: 44.5 ± 1.4-fold in vitro, CD, native gel electrophoresis Cell line: HEK293T and HeLa AD Lau et al. 2024

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  1. RNA 31: 1053-1080