Circular RNA (circRNA)

Circular RNAs (circRNAs) are a unique class of single-stranded RNA molecules characterized by a covalently closed loop structure, which is formed through a non-canonical splicing process called back-splicing. Unlike linear messenger RNAs, circRNAs lack 5' caps and 3' poly(A) tails, making them highly resistant to exonuclease-mediated degradation and providing them with a significantly longer half-life in the cytoplasm (Kristensen et al., 2019). Biologically, they function as 'microRNA sponges' that sequester miRNAs to prevent them from binding to their target mRNAs, and they also serve as scaffolds for protein complexes or templates for the translation of novel peptides (Hansen et al., 2013; Pamudurti et al., 2017). Dysregulation of circRNA expression is frequently observed in various diseases, particularly in cancer where they can drive tumor progression or act as suppressors (Chen et al., 2021). In the pharmaceutical industry, circRNAs are being investigated both as therapeutic targets for knockdown and as a robust platform for RNA-based medicines due to their superior stability compared to linear mRNA (Wesselhoeft et al., 2018). Furthermore, their abundance and stability in biofluids like blood and exosomes make them promising candidates for non-invasive diagnostic and prognostic biomarkers.

Other names

circRNANon-coding circular RNABack-spliced RNACircular non-coding RNA

Therapeutic strategies targeting circular RNA involve the use of antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) to induce the degradation of disease-promoting circRNAs via RNase H or the RNA-induced silencing complex (RISC). Conversely, synthetic circRNAs are being developed as a therapeutic platform to provide stable, long-lasting protein expression or to act as molecular decoys that sequester pathogenic microRNAs or proteins (Wesselhoeft et al., 2018; Kristensen et al., 2019).