Oncolytic Activity of Targeted Picornaviruses Formulated as Synthetic Infectious RNA

Elsedawy, Noura B.; Nace, Rebecca A.; Russell, Stephen J.; Schulze, Autumn J

doi:10.1016/j.omto.2020.05.003

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…As a possible reason for these observations, He et al suggested that the miR-TS probably disturbed the higher-order RNA structure of the viral genome [ 137 ]. This assessment is in line with another report showing delayed propagation of CVA21 from infectious viral RNA after insertion of miR-TS into a stem loop structure of the 3′-UTR which is important for viral RNA synthesis and poly(A) tail elongation [ 139 ]. Nevertheless, several studies recently demonstrated that miR-TS can also be inserted into the 3′-UTR of CVB3 without affecting virus propagation.…”

Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationsupporting

confidence: 91%

Coxsackievirus B3—Its Potential as an Oncolytic Virus

Geisler

Hazini

Heimann

et al. 2021

Viruses

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Oncolytic virotherapy represents one of the most advanced strategies to treat otherwise untreatable types of cancer. Despite encouraging developments in recent years, the limited fraction of patients responding to therapy has demonstrated the need to search for new suitable viruses. Coxsackievirus B3 (CVB3) is a promising novel candidate with particularly valuable features. Its entry receptor, the coxsackievirus and adenovirus receptor (CAR), and heparan sulfate, which is used for cellular entry by some CVB3 variants, are highly expressed on various cancer types. Consequently, CVB3 has broad anti-tumor activity, as shown in various xenograft and syngeneic mouse tumor models. In addition to direct tumor cell killing the virus induces a strong immune response against the tumor, which contributes to a substantial increase in the efficiency of the treatment. The toxicity of oncolytic CVB3 in healthy tissues is variable and depends on the virus strain. It can be abrogated by genetic engineering the virus with target sites of microRNAs. In this review, we present an overview of the current status of the development of CVB3 as an oncolytic virus and outline which steps still need to be accomplished to develop CVB3 as a therapeutic agent for clinical use in cancer treatment.

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Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationsupporting

confidence: 91%

Coxsackievirus B3—Its Potential as an Oncolytic Virus

Geisler

Hazini

Heimann

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…miRNA connects lncRNA and mRNA in various cancers, including HCC, acting as a bridge for the ceRNA network. 78 , 79 , 80 , 81 miR-96 reduces HCC migration, functioning as a therapeutic target in this disease. 82 miR-221-3p promotes HCC by downregulating the expression of O6-methylguanine-DNA methyltransferase.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

Zhang

Shi

Liu

et al. 2021

Molecular Therapy - Nucleic Acids

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Hepatocellular carcinoma (HCC) remains an extremely lethal disease worldwide. High-throughput methods have revealed global transcriptome dysregulation; however, a comprehensive investigation of the complexity and behavioral characteristics of the competing endogenous RNA (ceRNA) network in HCC is lacking. In this study, we extracted the transcriptome (RNA) sequencing data of 371 HCC patients from The Cancer Genome Atlas platform. With the comparison of the high Myc expression (Myc high ) tumor and low Myc expression (Myc low ) tumor groups in HCC, we identified 1,125 differentially expressed (DE) mRNAs, 589 long non-coding RNAs (lncRNAs), and 93 microRNAs (miRNAs). DE RNAs predicted the interactions necessary to construct an associated Myc ceRNA network, including 19 DE lncRNAs, 5 miRNAs, and 72 mRNAs. We identified a significant signature (long intergenic non-protein-coding [LINC] RNA 2691 [LINC02691] and LINC02499) that effectively predicted overall survival and had protective effects. The target genes of microRNA (miR)-212-3p predicted to intersect with DE mRNAs included SEC14-like protein 2 (SEC14L2) and solute carrier family 6 member 1 (SLC6A1), which were strongly correlated with survival and prognosis. With the use of the lncRNA-miRNA-mRNA axis, we constructed a ceRNA network containing four lncRNAs (LINC02691, LINC02499, LINC01354, and NAV2 antisense RNA 4), one miRNA (miR-212-3p), and two mRNAs (SEC14L2 and SLC6A1). Overall, we successfully constructed a mutually regulated ceRNA network and identified potential precision-targeted therapies and prognostic biomarkers.

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“…miRNA-targeting elements inserted within the viral genome target picornaviruses for degradation in healthy tissues expressing the cognate miRNA, while replication occurs unencumbered in neoplastic tissues where the cognate miRNA is not expressed [ 116 ]. This approach was shown to reliably eliminate fatal CAV21-associated myotoxicity in OV mouse models, both in the infectious RNA and viral particle formulation [ 117 – 119 ]. The use of miRNA-targeting elements not only controls oncolytic picornavirus permissivity and hence tissue-specific toxicities, but also provides an excellent safety platform to investigate the impact on oncolytic activity of other genome elements.…”

Section: Applicationsmentioning

confidence: 99%

The long-lasting enigma of polycytidine (polyC) tract

2021

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Long polycytidine (polyC) tracts varying in length from 50 to 400 nucleotides were first described in the 5′-noncoding region (NCR) of genomes of picornaviruses belonging to the Cardio- and Aphthovirus genera over 50 years ago, but the molecular basis of their function is still unknown. Truncation or complete deletion of the polyC tracts in picornaviruses compromises virulence and pathogenicity but do not affect replicative fitness in vitro, suggesting a role as “viral security” RNA element. The evidence available suggests that the presence of a long polyC tract is required for replication in immune cells, which impacts viral distribution and targeting, and, consequently, pathogenic progression. Viral attenuation achieved by reduction of the polyC tract length has been successfully used for vaccine strategies. Further elucidation of the role of the polyC tract in viral replication cycle and its connection with replication in immune cells has the potential to expand the arsenal of tools in the fight against cancer in oncolytic virotherapy (OV). Here, we review the published data on the biological significance and mechanisms of action of the polyC tract in viral pathogenesis in Cardio- and Aphthoviruses.

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Oncolytic Activity of Targeted Picornaviruses Formulated as Synthetic Infectious RNA

Cited by 12 publications

References 43 publications

Coxsackievirus B3—Its Potential as an Oncolytic Virus

Coxsackievirus B3—Its Potential as an Oncolytic Virus

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

The long-lasting enigma of polycytidine (polyC) tract

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