In vitro transcribed circRNA as a therapeutic agent for cancer

RNA therapy represents an innovative approach for cancer treatment, with several RNA-based therapeutics having received approval from the US Food and Drug Administration. Circular RNA (circRNA), a closed-loop RNA molecule characterized by its high stability, plays a significant role in regulating biological processes by modulating gene expression and facilitating protein translation. Given its unique structure and diverse functionalities, the delivery of exogenous circRNA has emerged as a novel strategy for cancer therapy. This review examines the mechanism underlying circRNA-mediated tumor therapy, emphasizing its various biological roles, including that of an RNA sponge, aptamer, gene editing tool, and facilitator of protein translation, and explores the therapeutic potential in oncology. The review provides a comprehensive discussion on the synthesis strategies of exogenous circRNA, based on T4 DNA ligase and the permuted introns-exons (PIE) method, as well as elucidating the purification techniques. This article also reviews prominent carriers currently employed for circRNA delivery, such as lipid nanoparticle (LNP), exosomes, and virus-like particle (VLP), with a particular emphasis on their application in cancer-targeted therapies. Finally, the review summarizes key challenges currently in the field along with viable solutions. It highlights the prospective role of artificial intelligence in enhancing circRNA delivery to facilitate precise cancer treatment based on exogenous circRNA.