Circular RNA vaccines against SARS-CoV-2 and emerging variants

Qu, Liang; Yi, Zongyi; Shen, Yonghang; Lin, Liang‐Hung; Chen, Feng; Xu, Yiyuan; Wu, Zeguang; Tang, Huixian; Zhang, Xiaoxue; Tian, Feng; Wang, Chunhui; Xiao, Xia; Dong, Xuan; Guo, Li; Lu, Shuaiyao; Yang, Chi; Tang, Cong; Yang, Yun; Wu, Yu; Wang, Junbin; Zhou, Yanan; Huang, Qing; Yisimayi, Ayijiang; Liu, Shuo; Huang, Weijin; Cao, Yunlong; Wang, Youchun; Zhou, Zhuo; Peng, Xiaozhong; Wang, Jianwei; Xie, X. Sunney; Wei, Wensheng

doi:10.1016/j.cell.2022.03.044

Cited by 329 publications

(265 citation statements)

References 107 publications

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“…119,120 One such circRNA encoded the trimeric RBD of the Omicron spike protein. 121 This vaccine candidate elicited high levels of neutralization antibody titers against the Omicron variant. However, it induced little neutralizing antibodies against other variants, while circRNA RBD-Delta vaccine could induce an intense antibody titer against Delta and Omicron.…”

Section: Developing Effective Vaccines Against the Omicron Variantmentioning

confidence: 99%

“…Circular RNAs (circRNAs) are covalently closed single‐stranded RNA transcripts produced by back‐splicing the pre‐mRNA of exons 119,120 . One such circRNA encoded the trimeric RBD of the Omicron spike protein 121 . This vaccine candidate elicited high levels of neutralization antibody titers against the Omicron variant.…”

Section: Strategies Against the Omicron Variantmentioning

confidence: 99%

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SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

109

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New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) constantly emerge through unmitigated spread of the virus in the ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), the latest variant of concern (VOC), has so far shown exceptional spread and infectivity and has established itself as the dominant variant in recent months. The SARS‐CoV‐2 spike glycoprotein is a key component for the recognition and binding to host cell angiotensin‐converting enzyme 2 receptors. The Omicron variant harbors a cluster of substitutions/deletions/insertions, and more than 30 mutations are located in spike. Some noticeable mutations, including K417N, T478K, N501Y, and P681H, are shared with the previous VOCs Alpha, Beta, Gamma, or Delta variants and have been proven to be associated with higher transmissibility, viral infectivity, and immune evasion potential. Studies have revealed that the Omicron variant is partially resistant to the neutralizing activity of therapeutic antibodies and convalescent sera, which poses significant challenges for the clinical effectiveness of the current vaccines and therapeutic antibodies. We provide a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant. This review, therefore, aims to provide information for further research efforts to prevent and contain the impact of new VOCs during the ongoing pandemic.

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Section: Developing Effective Vaccines Against the Omicron Variantmentioning

confidence: 99%

Section: Strategies Against the Omicron Variantmentioning

confidence: 99%

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

109

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“…RNA circularization leads to enhanced stability of the mRNA and greater efficiency in the production of the target protein [ 55 ]. Moreover, a circular mRNA vaccine could be stored at room temperature [ 60 ]. As a result, manufacturing and implementation costs would be significantly lower.…”

Section: Mrna Vaccinementioning

confidence: 99%

Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

et al. 2022

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The seasonal flu vaccine is, essentially, the only known way to prevent influenza epidemics. However, this approach has limited efficacy due to the high diversity of influenza viruses. Several techniques could potentially overcome this obstacle. A recent first-in-human study of a chimeric hemagglutinin-based universal influenza virus vaccine demonstrated promising results. The coronavirus pandemic triggered the development of fundamentally new vaccine platforms that have demonstrated their effectiveness in humans. Currently, there are around a dozen messenger RNA and self-amplifying RNA flu vaccines in clinical or preclinical trials. However, the applicability of novel approaches for a universal influenza vaccine creation remains unclear. The current review aims to cover the current state of this problem and to suggest future directions for RNA-based flu vaccine development.

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“…The researchers hypothesized that unlike current DNA vaccines, which use linear mRNA molecules to produce antigens, the circular structure of circRNAs would be more stable in the body. Experimental data from mouse and rhesus monkey models strongly support the idea that the coronavirus S protein antigen produced by the circular RNA vaccine has a longer half-life in laboratory animals than the linear mRNA vaccine and is effective in triggering an immune response [ 138 ]. At the same time, the circular RNA vaccine made with the template of Delta strain showed good protection against Alpha, Beta, Delta and Omicron strains.…”

Section: Opportunities and Challenges Of Circrna-based Therapeutic Te...mentioning

confidence: 99%

Circular RNAs Acting as miRNAs’ Sponges and Their Roles in Stem Cells

Xiao

Joseph

Xia

et al. 2022

JCM

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Circular RNAs (circRNAs), a novel type of endogenous RNAs, have become a subject of intensive research. It has been found that circRNAs are important players in cell differentiation and tissue homeostasis, as well as disease development. Moreover, the expression of circRNAs is usually not correlated with their parental gene expression, indicating that they are not only a steady-state by-product of mRNA splicing but a product of variable splicing under novel regulation. Sequence conservation analysis has also demonstrated that circRNAs have important non-coding functions. CircRNAs exist as a covalently closed loop form in mammalian cells, where they regulate cellular transcription and translation processes. CircRNAs are built from pre-messenger RNAs, and their biogenesis involves back-splicing, which is catalyzed by spliceosomes. The splicing reaction gives rise to three different types of intronic, exotic and exon–intron circular RNAs. Due to higher nuclease stability and longer half lives in cells, circRNAs are more stable than linear RNAs and have enormous clinical advantage for use as diagnostic and therapeutic biomarkers for disease. In recent years, it has been reported that circRNAs in stem cells play a crucial role in stem cell function. In this article, we reviewed the general feature of circRNAs and the distinct roles of circRNAs in stem cell biology, including regulation of stem cell self-renewal and differentiation. CircRNAs have shown unique expression profiles during differentiation of stem cells and could serve as promising biomarkers of these cells. As circRNAs play pivotal roles in stem cell regulation as well as the development and progression of various diseases, we also discuss opportunities and challenges of circRNA-based treatment strategies in future effective therapies for promising clinical applications.

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Circular RNA vaccines against SARS-CoV-2 and emerging variants

Cited by 329 publications

References 107 publications

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

Circular RNAs Acting as miRNAs’ Sponges and Their Roles in Stem Cells

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