Targeting circular RNAs as a therapeutic approach: current strategies and challenges

Abstract

Significant progress has been made in circular RNA (circRNA) research in recent years. Increasing evidence suggests that circRNAs play important roles in many cellular processes, and their dysregulation is implicated in the pathogenesis of various diseases. CircRNAs are highly stable and usually expressed in a tissue- or cell type-specific manner. Therefore, they are currently being explored as potential therapeutic targets. Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies, respectively. These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems. Furthermore, recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner. While still in the early stages of development, the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency. In this review, we describe circRNA properties and functions and highlight their significance in disease. We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach. Lastly, we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.

CircITCH: A Circular RNA With Eminent Roles in the Carcinogenesis

“…CircITCH, as a tumor suppressor circRNA can be utilized in therapeutic regimens for cancers. Delivery methods include nanoparticles and exosome-based methods (40). Artificial circRNAs have been successfully used as miRNA sponges in recent years (41).…”

The Value of Circulating Circular RNA in Cancer Diagnosis, Monitoring, Prognosis, and Guiding Treatment

“…Recently, several approaches have been developed to study circRNAs and target circRNAs for therapeutic purposes of cancer in vivo . The primary strategy is to intervene in cancer carcinogenesis, metastasis, apoptosis, and drug resistance by knocking down or overexpressing circRNAs, including circRNA knockdown strategies mediated by siRNA, short hairpin RNA (shRNA), ASO, and CRISPR/cas9 ( 109 ) ( Figures 3A –D ), the circRNA overexpression strategies mediated by vector and synthesis of circRNAs ( 110 , 111 ), and circRNA delivery strategies mediated by exosome or nanoparticle ( Figures 3 E, F ) ( 112 , 113 ). Numerous studies have revealed that using siRNAs to target degradation or knock down the expression of circRNAs in vivo or in vitro is the most commonly used strategy for cancer therapy with circRNAs as the therapeutic target ( 114 ).…”

The Emerging Functions of Circular RNAs in Bladder Cancer

“…However, chemotherapy resistance often leads to tumor recurrence and progression. Several studies have reported the relationship between circRNAs and chemotherapeutic resistance, suggesting that circRNAs may be potential therapeutic targets [150][151][152][153][154]. A study by Yuan et al showed that upregulation of circular RNA Cdr1as is related to cisplatin sensitivity in BC patients by upregulating expression of APAF1 via miR-1270 repression [155].…”