Year: 2025
Type: article
Abstract: RNAs have recently emerged as versatile therapeutic targets, broadening the scope of drug discovery beyond the conventional protein-centered paradigm. Small-molecule-induced RNA degradation has been established as a promising approach, with novel modalities such as Ribonuclease-Targeting Chimeras (RIBOTACs), bleomycin-conjugated degraders, and imidazole-based RNA degrader demonstrating strong potential. These strategies selectively eliminate disease-associated RNAs by harnessing endogenous ribonucleases, redirecting the nucleic acid-cleaving activity of natural products, or incorporating catalytic warheads. Recent studies have validated therapeutic applications across cancer, neurodegenerative disorders, and viral infections, underscoring the wide-ranging impact of this strategy. Nevertheless, key challenges remain, including the development of more potent recruiters, diversification of degradation mechanisms, optimization of linker chemistry, and overcoming pharmacokinetic limitations. With continued innovation, RNA degraders are expected to evolve into a robust therapeutic platform that expands the druggable space and enables new treatment opportunities for diseases once considered untreatable.
Authors: Sivakumar Komachankandy, Yeongju Lee
Institution: Pusan National University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G1871637035, G4338546216
OpenAlex ID: W4415928934