Interrogation of mirror-image l-RNA-protein interactions reveals key mechanisms of single-stranded G-rich l-RNA cytotoxicity and a potential mitigation strategy.

ABSTRACT: l-Oligonucleotides (ONs), the synthetic enantiomers of native d-nucleic acids, are being increasingly utilized in the development of diverse biomedical technologies, including molecular imaging tools, diagnostic biosensors, and aptamer-based therapeutics. Nevertheless, our understanding of how l-ONs behave in living systems falls far short of native d-ONs. In particular, despite the potential for an abundant l-ON-protein interactome, the extent to which l-ONs bind to endogenous proteins and the consequences of these interactions are unknown, posing a major hurdle towards engineering functional l-ONs with predictable intracellular behaviours. Towards closing this knowledge gap, we now report the first l-ON-protein interactome, revealing that a wide-range of nuclear proteins have the potenti

SUBMITTER: Yu CH 

PROVIDER: S-EPMC11955919 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature