G-quadruplex structures of nucleic acids have been a focus of study for anticancer or other diseases therapy for long time. Nonetheless, there is still no G4-targeting drugs available for clinical use. Now, researchers have developed a lot of fundamental knowledge on G4s and many G4-targeting small-molecules. What we are actually lacking and what we need in order to get into another milestone in the future?
Harsh Sharma
Better Molecular Tools Develop high-resolution imaging tools and chemical probes to visualize G4 structures in living cells. Employ CRISPR-based approaches to study G4 functional relevance in specific genes. Advanced Small Molecule Design Use AI and machine learning for rational design of G4 ligands with enhanced specificity and drug-like properties. Explore bifunctional molecules (e.g., PROTACs) that target G4s while recruiting cellular machinery to degrade associated proteins. Integrated Research Approaches Combine structural biology, genomics, and chemical biology to identify actionable G4 targets. Employ systems biology to study the broader impact of G4 stabilization on cellular pathways. Targeting RNA G-Quadruplexes RNA G4s are emerging as promising targets due to their roles in translation regulation and splicing. Develop ligands with specificity for RNA vs. DNA G4s and test their therapeutic potential. Collaboration and Data Sharing Foster collaborative networks between academia, industry, and clinical researchers to accelerate translation. Develop standardized protocols for G4-targeting studies to improve reproducibility and comparability.
What Is Needed for the Next Milestone
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