Compared with conventional RNA therapeutic modalities, circRNA has potential to achieve potent pharmaceutical effects with simplified manufacturing process. However, to date, circRNA-based therapeutic approaches have only been applied in preclinical studies. There are still some challenges using circRNA as a clinical tool to treat diseases such as low circularization efficiency, high cost of reagents, mis-splicd byproducts, synthetic circRNA immunogenicity, requiring extensive and in-depth research.