Research Progress on Circular RNA Vaccines

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jan 30

PMID 36713460

Authors

Yu Bai

Dong Liu

Qian He

Jianyang Liu

Qunying Mao

Zhenglun Liang

Affiliations

Soon will be listed here.

Abstract

Owing to the success of linear mRNA coronavirus disease 2019 (COVID-19) vaccines, biopharmaceutical companies and research teams worldwide have attempted to develop more stable circular RNA (circRNA) vaccines and have achieved some preliminary results. This review aims to summarize key findings and important progress made in circRNA research, the metabolism and biological functions of circRNAs, and research progress and production process of circRNA vaccines. Further, considerations regarding the quality control of circRNA vaccines are highlighted herein, and the main challenges and problem-solving strategies in circRNA vaccine development and quality control are outlined to provide a reference for circRNA vaccine-related research.

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References

Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A . Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013; 495(7441):333-8. DOI: 10.1038/nature11928. View

Tagawa T, Koparde V, Ziegelbauer J . Identifying and characterizing virus-encoded circular RNAs. Methods. 2021; 196:129-137. PMC: 8445388. DOI: 10.1016/j.ymeth.2021.03.004. View

Kariko K, Buckstein M, Ni H, Weissman D . Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity. 2005; 23(2):165-75. DOI: 10.1016/j.immuni.2005.06.008. View

Lamb Y . BNT162b2 mRNA COVID-19 Vaccine: First Approval. Drugs. 2021; 81(4):495-501. PMC: 7938284. DOI: 10.1007/s40265-021-01480-7. View

Xu X, Zhang J, Tian Y, Gao Y, Dong X, Chen W . CircRNA inhibits DNA damage repair by interacting with host gene. Mol Cancer. 2020; 19(1):128. PMC: 7446195. DOI: 10.1186/s12943-020-01246-x. View

Cooper S, Wadsworth E, Ochsenreiter T, Ivens A, Savill N, Schnaufer A . Assembly and annotation of the mitochondrial minicircle genome of a differentiation-competent strain of Trypanosoma brucei. Nucleic Acids Res. 2019; 47(21):11304-11325. PMC: 6868439. DOI: 10.1093/nar/gkz928. View

Wadman M . The overlooked superpower of mRNA vaccines. Science. 2021; 373(6554):479. DOI: 10.1126/science.373.6554.479. View

Wawrzyniak O, Zarebska Z, Kuczynski K, Gotz-Wieckowska A, Rolle K . Protein-Related Circular RNAs in Human Pathologies. Cells. 2020; 9(8). PMC: 7463956. DOI: 10.3390/cells9081841. View

Han J, Li S, Feng Y, He Y, Hong W, Ye Z . A novel circular RNA (hsa_circ_0059930)-mediated miRNA-mRNA axis in the lipopolysaccharide-induced acute lung injury model of MRC-5 cells. Bioengineered. 2021; 12(1):1739-1751. PMC: 8806270. DOI: 10.1080/21655979.2021.1916276. View

10.

Packer M, Gyawali D, Yerabolu R, Schariter J, White P . A novel mechanism for the loss of mRNA activity in lipid nanoparticle delivery systems. Nat Commun. 2021; 12(1):6777. PMC: 8608879. DOI: 10.1038/s41467-021-26926-0. View

11.

Kuznetsova I, Rackham O, Filipovska A . Investigating Mitochondrial Transcriptomes and RNA Processing Using Circular RNA Sequencing. Methods Mol Biol. 2020; 2192:43-57. DOI: 10.1007/978-1-0716-0834-0_4. View

12.

Wang Y, Wang Z . Efficient backsplicing produces translatable circular mRNAs. RNA. 2014; 21(2):172-9. PMC: 4338345. DOI: 10.1261/rna.048272.114. View

13.

Zhou Y, Wu J, Yao S, Xu Y, Zhao W, Tong Y . DeepCIP: A multimodal deep learning method for the prediction of internal ribosome entry sites of circRNAs. Comput Biol Med. 2023; 164:107288. DOI: 10.1016/j.compbiomed.2023.107288. View

14.

Salzman J, Gawad C, Wang P, Lacayo N, Brown P . Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012; 7(2):e30733. PMC: 3270023. DOI: 10.1371/journal.pone.0030733. View

15.

Di Timoteo G, Rossi F, Bozzoni I . Circular RNAs in cell differentiation and development. Development. 2020; 147(16). DOI: 10.1242/dev.182725. View

16.

Liu C, Chen L . Circular RNAs: Characterization, cellular roles, and applications. Cell. 2022; 185(12):2016-2034. DOI: 10.1016/j.cell.2022.04.021. View

17.

He Q, Mao Q, Zhang J, Bian L, Gao F, Wang J . COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations. Front Immunol. 2021; 12:669339. PMC: 8071852. DOI: 10.3389/fimmu.2021.669339. View

18.

Liu J, Mao Q, Wu X, He Q, Bian L, Bai Y . Considerations for the Feasibility of Neutralizing Antibodies as a Surrogate Endpoint for COVID-19 Vaccines. Front Immunol. 2022; 13:814365. PMC: 9092276. DOI: 10.3389/fimmu.2022.814365. View

19.

Dolgin E . The tangled history of mRNA vaccines. Nature. 2021; 597(7876):318-324. DOI: 10.1038/d41586-021-02483-w. View

20.

Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O . Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 2017; 66(1):22-37.e9. PMC: 5387670. DOI: 10.1016/j.molcel.2017.02.017. View