Marker gene transfer into human haemopoietic cells using a herpesvirus saimiri-based vector

Doody, Gina M.; Leek, J.P.; Bali, Anu; Ensser, Armin; Markham, Alex F.; Wynter, Erika A. de

doi:10.1038/sj.gt.3302422

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…Moreover, green fluorescent protein (GFP) expression from the HVS episome was maintained in terminally differentiated macrophages (21). Similar results were also observed upon human hemopoietic progenitor cell differentiation toward the erythroid lineage (33). Therefore, HVS could potentially be capable of maintaining its episome by reprogramming cells without transgene silencing.…”

supporting

confidence: 65%

Potential of Herpesvirus Saimiri-Based Vectors To Reprogram a Somatic Ewing's Sarcoma Family Tumor Cell Line

Brown

Unger

Whitehouse

2013

J Virol

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cHerpesvirus saimiri (HVS) infects a range of human cell types with high efficiency. Upon infection, the viral genome can persist as high-copy-number, circular, nonintegrated episomes that segregate to progeny cells upon division. This allows HVS-based vectors to stably transduce a dividing cell population and provide sustained transgene expression in vitro and in vivo. Moreover, the HVS episome is able to persist and provide prolonged transgene expression during in vitro differentiation of mouse and human hemopoietic progenitor cells. Together, these properties are advantageous for induced pluripotent stem cell (iPSC) technology, whereby stem cell-like cells are generated from adult somatic cells by exogenous expression of specific reprogramming factors. Here we assess the potential of HVS-based vectors for the generation of induced pluripotent cancer stem-like cells (iPCs). We demonstrate that HVS-based exogenous delivery of Oct4, Nanog, and Lin28 can reprogram the Ewing's sarcoma family tumor cell line A673 to produce stem cell-like colonies that can grow under feeder-free stem cell culture conditions. Further analysis of the HVS-derived putative iPCs showed some degree of reprogramming into a stem cell-like state. Specifically, the putative iPCs had a number of embryonic stem cell characteristics, staining positive for alkaline phosphatase and SSEA4, in addition to expressing elevated levels of pluripotent marker genes involved in proliferation and self-renewal. However, differentiation trials suggest that although the HVS-derived putative iPCs are capable of differentiation toward the ectodermal lineage, they do not exhibit pluripotency. Therefore, they are hereby termed induced multipotent cancer cells.

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supporting

confidence: 65%

Potential of Herpesvirus Saimiri-Based Vectors To Reprogram a Somatic Ewing's Sarcoma Family Tumor Cell Line

Brown

Unger

Whitehouse

2013

J Virol

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“…The ability of HVS to infect and persist in primate haematopoietic cells suggests it could be developed for the treatment of disorders affecting the erythroid lineage [Doody et al, 2005]. Moreover, the ability of HVS to transform human T cells has led to the development of HVS as a potential episomal vector for adoptive immunotherapy of infectious and malignant diseases [Hiller et al, 2000a, Hiller et al, 2000b, Knappe et al, 2000.…”

Section: Applications Of Hvs-based Vectorsmentioning

confidence: 98%

“…Therefore, HVS infectivity of a CD34+ cell population isolated from umbilical cord blood was assessed, in particular the ability of HVS to infect stem and myeloid progenitor cells. Results demonstrated HVS infection and persistence in primitive human haematopoietic progenitor cells and the presence of the HVS episome had no effect on erythroid lineage differentiation using both standard clonogenic colony-forming cell assays and liquid differentiation cultures [Doody et al, 2005].…”

Section: In Vitro Analysismentioning

confidence: 99%

Herpesvirus Saimiri-Based Gene Delivery Vectors

Griffiths¹,

Boyne²,

Whitehouse³

2006

CGT

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Herpesviruses possess a number of characteristics which make them promising gene delivery vectors. These include their capacity to package large amounts of heterologous DNA and an ability to establish persistent, lifelong infections, where the viral genome remains as a circular non-integrated episome. Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus and is currently being developed as a potential gene delivery vector. In addition to the above properties, HVS-based vectors have the ability to infect a wide range of human cell lines and primary cultures with high efficiencies. Moreover, upon infection the viral genome persists as high copy number, circular, non-integrated episomes which segregate to progeny cells upon division. This allows the HVS-based vector to stably transduce a dividing cell population and provide sustained heterologous gene expression. As such, it offers the characteristics of an artificial chromosome combined with a highly efficient delivery system. This review aims to describe the assessment of HVS-based vectors in both in vitro and in vivo studies, highlighting new developments and possible applications for the treatment of genetic diseases.

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“…This technique, although successful was time consuming and required replication-competent viruses. Another strategy was the use of an overlapping cosmid library containing the genome of the HVS C488 strain [15, 16]. This system was quicker than the homologous recombination method above; however, the transfection of multiple cosmid constructs into the OMK cells has a low efficiency.…”

Section: Introductionmentioning

confidence: 99%

“…HVS has been shown to infect several human haematopoietic cell lines [6, 14, 16]. Moreover, the virus has been used to infect totipotent mouse ES cells, and GFP transgene expression was maintained throughout differentiation of those cells into mature haematopoietic cells [25].…”

Section: Introductionmentioning

confidence: 99%

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

Turrell

Whitehouse

2010

BioMed Research International

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Herpesvirus saimiri (HVS) is a gamma herpesvirus with several properties that make it an amenable gene therapy vector; namely its large packaging capacity, its ability to persist as a nonintegrated episome, and its ability to infect numerous human cell types. We used RecA-mediated recombination to develop an HVS vector with a mutated virion protein. The heparan sulphate-binding region of HVS ORF51 was substituted for a peptide sequence which interacts with somatostatin receptors (SSTRs), overexpressed on hepatocellular carcinoma (HCC) cells. HVS mORF51 showed reduced infectivity in non-HCC human cell lines compared to wild-type virus. Strikingly, HVS mORF51 retained its ability to infect HCC cell lines efficiently. However, neutralisation assays suggest that HVS mORF51 has no enhanced binding to SSTRs. Therefore, mutation of the ORF51 glycoprotein has specifically targeted HVS to HCC cell lines by reducing the infectivity of other cell types; however, the mechanism for this targeting is unknown.

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Marker gene transfer into human haemopoietic cells using a herpesvirus saimiri-based vector

Cited by 7 publications

References 23 publications

Potential of Herpesvirus Saimiri-Based Vectors To Reprogram a Somatic Ewing's Sarcoma Family Tumor Cell Line

Potential of Herpesvirus Saimiri-Based Vectors To Reprogram a Somatic Ewing's Sarcoma Family Tumor Cell Line

Herpesvirus Saimiri-Based Gene Delivery Vectors

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

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