Mutation of Herpesvirus Saimiri ORF51 Glycoprotein Specifically Targets Infectivity to Hepatocellular Carcinoma Cell Lines

Turrell, Susan J.; Whitehouse, Adrian

doi:10.1155/2011/785158

Cited by 5 publications

(3 citation statements)

References 53 publications

(60 reference statements)

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“…The HVS ∆71-73 BAC construct is described elsewhere (9). It is based on a bacterial artificial chromosome (BAC) with the BAC elements from the F-plasmid cloned into open reading frame (ORF) 15 of HVS strain A11 S4 (29,30). This insert also contains cassettes for hygromycin phosphotransferase (Hyg R ) and dsRed, as well as a unique I-PpoI restriction site to allow conventional cloning into the 160 kb viral genome.…”

Section: Methodsmentioning

confidence: 99%

A Herpesvirus saimiri-based vector expressing TRAIL induces cell death in human carcinoma cell lines and multicellular spheroid cultures

et al. 2012

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Abstract. Herpesvirus saimiri (HVS) is capable of infecting a range of human carcinoma cell types with high efficiency and the viral genome persists as high copy number, circular, non-integrated episomes which segregate to progeny upon cell division. This allows HVS-based vectors to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time both in vitro and in vivo. Moreover, the insertion of a bacterial artificial chromosome cassette into the HVS genome simplifies the incorporation of large amounts of heterologous DNA for gene delivery. Herein we have produced a recombinant HVS-based vector containing full-length human TRAIL under the control of the α-survivin promoter, and subsequently challenged a variety of cancer cell lines with this vector. The TRAIL transgene was expressed in infected colorectal SW480 cells, causing considerable apoptosis induction. Apoptosis was also observed when several other cancer cell lines derived from different tissues were infected. Moreover, co-treatment with Jak inhibitor AG490 led to the disruption of spheroid cultures grown from the melanoma Mel888 line. These data suggest that an HVS gene therapy vector expressing TRAIL could be an effective treatment against cancer.

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Section: Methodsmentioning

confidence: 99%

A Herpesvirus saimiri-based vector expressing TRAIL induces cell death in human carcinoma cell lines and multicellular spheroid cultures

et al. 2012

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“…The subsequent recombinant virus appeared to infect the carcinoma cells as well as the wild-type virus, while showing reduced infectivity for other cell lines. The reason for these observations is unclear [ 20 ]. In conclusion, herpesviruses remain promising as candidates for oncolytic therapy as they can be redirected to tumor cells and are considered reasonably safe due to the induction of a self-limited disease in humans.…”

Section: Modification Of Viral Surface Proteinsmentioning

confidence: 99%

Retargeting of Viruses to Generate Oncolytic Agents

Verheije

Rottier

2012

Advances in Virology

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Oncolytic virus therapy is based on the ability of viruses to effectively infect and kill tumor cells without destroying the normal tissues. While some viruses seem to have a natural preference for tumor cells, most viruses require the modification of their tropism to specifically enter and replicate in such cells. This review aims to describe the transductional targeting strategies currently employed to specifically redirect viruses towards surface receptors on tumor cells. Three major strategies can be distinguished; they involve (i) the incorporation of new targeting specificity into a viral surface protein, (ii) the incorporation of a scaffold into a viral surface protein to allow the attachment of targeting moieties, and (iii) the use of bispecific adapters to mediate targeting of a virus to a specified moiety on a tumor cell. Of each strategy key features, advantages and limitations are discussed and examples are given. Because of their potential to cause sustained, multiround infection—a desirable characteristic for eradicating tumors—particular attention is given to viruses engineered to become self-targeted by the genomic expression of a bispecific adapter protein.

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“…The HVS-GFP-BAC utilised is a recombinant strain of HVS A11-S4 with a bacterial artificial chromosome (BAC) cassette inserted into ORF 15 (31,32). The BAC cassette confers chloramphenicol and hygromycin resistance, and contains a GFP expression marker and a unique I-PpoI restriction site.…”

Section: Construction Of Apc-expressing Hvs Vectorsmentioning

confidence: 99%

Herpesvirus saimiri-mediated delivery of the adenomatous polyposis coli tumour suppressor gene reduces proliferation of colorectal cancer cells

Macnab

Turrell²,

Carr³

et al. 2011

Int J Oncol

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Abstract. Colorectal cancer (CRC) is a major cause of cancerrelated mortality. A contributing factor to the progression of this disease is sporadic or hereditary mutation of the adenomatous polyposis coli (APC) gene, a negative regulator of the Wnt signalling pathway. Inherited mutations in APC cause the disorder familial adenomatous polyposis (FAP), which leads to CRC development in early adulthood. However, the gene is also disrupted in some 60% of sporadic cancers. Restoration of functional APC may slow the growth of CRC by negatively regulating proliferation-associated genes such as c-myc. Therefore, we have cloned the cDNA of the APC tumour suppressor gene into a replication competent Herpesvirus saimiri (HVS)-based vector to assess APC gene delivery in SW480 and SW620 CRC cell lines. Our results demonstrate that full length APC protein was efficiently expressed from the HVS vector and that transgene expression inhibited proliferation of both the SW480 and the metastatic SW620 cancer cell lines. Moreover, a sustained effect could be observed for at least 8 weeks after initial infection in SW480 cells. In addition, monolayer wounding assays showed a marked reduction in proliferation and migration in HVS-GFP-APC infected cells. We believe that this is the first instance of infectious delivery and APC cDNA expression from a virus-based vector.

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Mutation of Herpesvirus Saimiri ORF51 Glycoprotein Specifically Targets Infectivity to Hepatocellular Carcinoma Cell Lines

Cited by 5 publications

References 53 publications

A Herpesvirus saimiri-based vector expressing TRAIL induces cell death in human carcinoma cell lines and multicellular spheroid cultures

A Herpesvirus saimiri-based vector expressing TRAIL induces cell death in human carcinoma cell lines and multicellular spheroid cultures

Retargeting of Viruses to Generate Oncolytic Agents

Herpesvirus saimiri-mediated delivery of the adenomatous polyposis coli tumour suppressor gene reduces proliferation of colorectal cancer cells

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