Anticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag

Sabbioni, Silvia; Callegari, Elisa; Spizzo, Riccardo; Veronese, Angelo; Altavilla, Giuseppe; Corallini, Alfredo; Negrini, Massimo

doi:10.1038/sj.cgt.7701014

Cited by 6 publications

(3 citation statements)

References 42 publications

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“…Short interfering RNAs designed to target the BKV T‐Ag were reported to restrain its expression in pRPc cell lines. Blocking of T‐Ag results in diminished growth rate of BKV‐transformed cells and thus suppresses tumorigenicity …”

Section: Antiviral Potential Of Sirnasmentioning

confidence: 99%

A review on current status of antiviral siRNA

Qureshi

Tantray

Kirmani

et al. 2018

Reviews in Medical Virology

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Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene-silencing phenomenon in which sequence-specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed.

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Section: Antiviral Potential Of Sirnasmentioning

confidence: 99%

A review on current status of antiviral siRNA

Qureshi

Tantray

Kirmani

et al. 2018

Reviews in Medical Virology

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“…Intratumoral delivery of anti-microRNA may help in silencing viral microRNA or viral-induced cellular microRNA, while RNA interference may turn off the expression of viral oncoproteins. RNA interference targeting LT-ag has been shown to abrogate HPyV replication in vitro and suppress tumor growth in vitro and in an animal model [ 180 , 212 , 213 , 214 , 215 , 216 , 217 ]. The use of exosomes as vaccines against cancer and infectious diseases has been suggested and exosomes pulsed with MCPyV LT-ag could be considered to treat MCPyV-positive MCC patients [ 187 , 218 ].…”

Section: Therapeutic Strategies Against Emerging Hallmarks Of Cancmentioning

confidence: 99%

The Role of Merkel Cell Polyomavirus and Other Human Polyomaviruses in Emerging Hallmarks of Cancer

Moens

Rasheed

Abdulsalam

et al. 2015

Viruses

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Polyomaviruses are non-enveloped, dsDNA viruses that are common in mammals, including humans. All polyomaviruses encode the large T-antigen and small t-antigen proteins that share conserved functional domains, comprising binding motifs for the tumor suppressors pRb and p53, and for protein phosphatase 2A, respectively. At present, 13 different human polyomaviruses are known, and for some of them their large T-antigen and small t-antigen have been shown to possess oncogenic properties in cell culture and animal models, while similar functions are assumed for the large T- and small t-antigen of other human polyomaviruses. However, so far the Merkel cell polyomavirus seems to be the only human polyomavirus associated with cancer. The large T- and small t-antigen exert their tumorigenic effects through classical hallmarks of cancer: inhibiting tumor suppressors, activating tumor promoters, preventing apoptosis, inducing angiogenesis and stimulating metastasis. This review elaborates on the putative roles of human polyomaviruses in some of the emerging hallmarks of cancer. The reciprocal interactions between human polyomaviruses and the immune system response are discussed, a plausible role of polyomavirus-encoded and polyomavirus-induced microRNA in cancer is described, and the effect of polyomaviruses on energy homeostasis and exosomes is explored. Therapeutic strategies against these emerging hallmarks of cancer are also suggested.

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“…22 As demonstrated by studies on the highly homologous SV40 virus, 23 the stable suppression of T-Ag expression in BKV-transformed cell lines should suppress the in vitro and in vivo Two siRNAs, namely siRNA 1390 and 714, were identified that abolish T-Ag expression and siRNA 1390 was chosen for this study. 24 To express stable 1390 siRNA, the vector psiBKVT-1390-hHGFPzeoG2 ( Figure 1a) was constructed, encoding the shRNA against T-Ag (shBKVT-1390) under the control of H1 RNA promoter. Twenty-four hours after transfection of psiBKVT-1390-hHGFPzeoG2 into pRPc cells, immunofluorescence analysis revealed that green fluorescent protein (GFP)-positive cells had a simultaneous marked reduction of the nuclear rhodamine fluorescence for T-Ag, demonstrating that shBKVT-1390 was active in suppressing T-Ag expression (Figure 1b).…”

mentioning

confidence: 99%

Use of herpes simplex virus type 1-based amplicon vector for delivery of small interfering RNA

et al. 2006

Self Cite

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Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis of mammalian cells. The use of DNA-based plasmid vectors to achieve transient and stable expression of siRNA has been developed to avoid the problems of double-stranded oligonucleotides transfection. These vectors direct the transcription of small hairpin RNAs (shRNAs) from a polymerase-III (H1 or U6)-RNA gene promoter. However, numerous disadvantages remain, including low transfection efficiency and difficulty in transfecting primary cells. To overcome some of these problems, the use of viral vectors for siRNA delivery has been described. Retroviral, adenoviral, adeno-associated and herpes viral shRNAs delivery systems have been successfully used to silence genes, in vitro and in vivo. The use of a herpes simplex virus type 1 (HSV-1)-based amplicon vector for siRNA delivery into mammalian cells, using human polyomavirus BK (BKV)-transformed cells as a model system is described. The results demonstrate the ability of amplicon vectors to inhibit the expression of BKV T-Ag and tumorigenicity of BKV-transformed cells. We show that the use of the amplicon vector is highly efficient for the delivery of siRNA molecules. The unique ability of these vectors to deliver multiple copies of siRNA may provide a useful tool in the development of novel anticancer therapy.

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Anticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag

Cited by 6 publications

References 42 publications

A review on current status of antiviral siRNA

A review on current status of antiviral siRNA

The Role of Merkel Cell Polyomavirus and Other Human Polyomaviruses in Emerging Hallmarks of Cancer

Use of herpes simplex virus type 1-based amplicon vector for delivery of small interfering RNA

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