Circular RNAs in and out of Cells: Therapeutic Usages of Circular RNAs

Abstract

RNAs are versatile molecules that are primarily involved in gene regulation and can thus be widely used to advance the fields of therapeutics and diagnostics. In particular, circular RNAs which are highly stable, have emerged as strong candidates for use on next-generation therapeutic platforms. Endogenous circular RNAs control gene regulatory networks by interacting with other biomolecules or through translation into polypeptides. Circular RNAs exhibit cell-type specific expression patterns, which can be altered in tissues and body fluids depending on pathophysiological conditions. Circular RNAs that are aberrantly expressed in diseases can function as biomarkers or therapeutic targets. Moreover, exogenous circular RNAs synthesized in vitro can be introduced into cells as therapeutic molecules to modulate gene expression networks in vivo. Depending on the purpose, synthetic circular RNA sequences can either be identical to endogenous circular RNA sequences or artificially designed. In this review, we introduce the life cycle and known functions of intracellular circular RNAs. The current stage of endogenous circular RNAs as biomarkers and therapeutic targets is also described. Finally, approaches and considerations that are important for applying the available knowledge on endogenous circular RNAs to design exogenous circular RNAs for therapeutic purposes are presented.

Brief guide to RNA sequencing analysis for nonexperts in bioinformatics

“…Here, we briefly describe methods regarding how to perform transcriptome analyses and a mini-collection of publicly available transcriptome data. Although detailed protocols, workflows, parameters, and versions for each tool need to be modified depending on the aims of experiments ( Hao et al, 2023 , Hong and Jeong, 2023 , Jang et al, 2022 , Ju et al, 2023 , Park et al, 2023 ), our guideline will be valuable for biologists who are not bioinformaticians to analyze their own and publicly available RNA-seq data. Users will need to refer to other papers for assessing microarray, scRNA sequencing data ( Ryu et al, 2023 , Hwang, 2023 , Kim, 2023 , Kim and Lee, 2023 ), and hardware requirements for transcriptome analysis, which we did not include in this guideline.…”

New insight into circRNAs: characterization, strategies, and biomedical applications

“…circRNA expression boxes in target cells may produce a large number of linear products in addition to target circRNA, which may adversely affect cells. We may directly introduce circRNA, which has been synthesized in vitro, into the target cells and deliver it with nonviral nanoparticles [ 45 , 130 , 192 , 204 ]. However, in vitro circularized RNAs generally induce extra coding genes or sequences and often activate remarkable immune responses and other unknown side effects.…”

Circular RNA: A promising new star of vaccine

“…Because circRNAs have a covalently closed structure and no termini, circRNAs are immune to degradation mediated by exonucleases, conserving a higher stability than their linear mRNA isoforms. [ 11 , 25 , 54 , 55 ] In mammalian cells, the intermediate half-life of circRNAs is at least 2.5 times more than that of their linear counterparts. [ 56 ] The safe antigen production of circRNA-based vaccines can be ensured by circRNAs’ ability to be expressed endogenously.…”