The herpes simplex virus amplicon: A new eucaryotic defective-virus cloning-amplifying vector

Spaete, Richard R.; Frenkel, Niza

doi:10.1016/0092-8674(82)90035-6

Cited by 496 publications

(295 citation statements)

References 33 publications

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“…Amplicons are defective, helper-dependent vectors that carry no viral genes and take advantage of the large carrier capacity of the virus particle to deliver long transgenic sequences [19, 20]. There is currently no other vector that equals the ability of amplicons to safely deliver almost 150 Kbp of foreign DNA to the nucleus of mammalian cells.…”

Section: Amplicon Vectorsmentioning

confidence: 99%

“…High-capacity vectors, such as HSV-1-derived amplicon vectors [19, 20], are extreme cases since they carry no virus genes and therefore express no virus functions in the transduced cells. This implies that all virus self-protective functions are absent, with the only exception of the functions carried by the structural proteins that are introduced in the cells during entry of vector particles, which have nevertheless a limited half-life and will soon disappear.…”

Section: Introductionmentioning

confidence: 99%

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Constitutive and Inducible Innate Responses in Cells Infected by HSV-1- Derived Amplicon Vectors

Tsitoura

Epstein

2010

TOVJ

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Amplicons are helper-dependent herpes simplex virus type 1 (HSV-1)-based vectors that can deliver very large foreign DNA sequences and, as such, are good candidates both for gene delivery and vaccine development. However, many studies have shown that innate constitutive or induced cellular responses, elicited or activated by the entry of HSV-1 particles, can play a significant role in the control of transgenic expression and in the induction of inflammatory responses. Moreover, transgene expression from helper-free amplicon stocks is often weak and transient, depending on the particular type of infected cells, suggesting that cellular responses could be also responsible for the silencing of amplicon-mediated transgene expression. This review summarizes the current experimental evidence underlying these latter concepts, focusing on the impact on transgene expression of very-early interactions between amplicon particles and the infected cells, and speculates on possible ways to counteract the cellular protective mechanisms, thus allowing stable transgene expression without enhancement of vector toxicity.

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Section: Amplicon Vectorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Constitutive and Inducible Innate Responses in Cells Infected by HSV-1- Derived Amplicon Vectors

Tsitoura

Epstein

2010

TOVJ

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“…19 Owing to a rolling mechanism of replication, multiple copies of the amplicon plasmid up to a maximum of 150 kb, the size of HSV-1 wild-type genome, can be packaged into viral particles. For HSV-1 helper virus-dependent amplicon vector generation, producer cells are infected with a replication-defective HSV-1 helper virus in addition to transduction with a transgene-carrying amplicon plasmid.…”

Section: Introductionmentioning

confidence: 99%

Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia

et al. 2005

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For leukemia vaccine generation, high-efficiency gene transfer is required to express immunomodulatory molecules that stimulate potent antileukemic immune responses. In this context, herpes simplex virus type-1 (HSV-1)-derived vectors have proven to be a promising tool for genetic modification of lymphoblastic leukemia cells. Yet, vector-associated viral protein expression might inadvertently modulate vaccine efficacy facilitating both immune evasion and immune stimulation. To explore the issue of immune-stimulation versus immune-suppression in immature lymphoblastic leukemia cells, two types of HSV-1 amplicon vectors, helper virus-dependent and helper virus-free that express the immunomodulatory molecules CD70 and IL-2, were compared with regard to their vector-associated immunomodulatory potential. We first established that lymphoblastic cell lines and primary acute lymphoblastic leukemia (ALL) cells express HSV receptor genes. Lymphoblastic cell lines were transduced with high efficiency, and in primary ALL cells high gene transfer rates of 47715 and 42714% were obtained with helper virus-dependent and -free HSV-1 amplicon vectors, respectively. The efficacy of the two amplicon vectors to induce antineoplastic responses was assessed in a vaccine setting in mice with pre-existing highly malignant lymphoblastic disease. Treatment of mice with vaccine cells transgenically expressing CD70+IL2 significantly suppressed lymphoblastic cell proliferation and improved survival. Of note, when helper virus-dependent HSV-1 amplicon vectors were used for vaccine preparation, the high immunogenic potential of the vector itself, in the absence of transgenic CD70+IL2 expression, seemed to be sufficient to mediate protection comparable to the antineoplastic response achieved by expression of immunomodulatory molecules. Thus for vaccine generation in B lymphoblastic leukemia, the immunogenic potential of HSV-1 helper virus-dependent amplicon vectors does provide additional benefit to the high transduction efficiency of HSV-1-derived vectors.

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“…The amplicon can be amplified and packaged into infectious HSV-1 virions in the presence of the helper virus. [27][28][29] This plasmid system permits easier cloning, and carries genomic information between procaryotic and eucaryotic cells as a shuttle vector. 30 The amplicon system retains the merits of HSV-1 vectors including high efficiency of gene transfer in vitro and in vivo, a wide range of hosts, and neurotropism.…”

Section: Introductionmentioning

confidence: 99%

Functional expression of ATM gene carried by HSV amplicon vector in vitro and in vivo

Shackelford

Manuszak

et al. 2003

Gene Ther

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Ataxia-telangiectasia (AT) is a human autosomal recessive disease with a pleiotropic phenotype characterized by cerebellar degeneration, immunodeficiency, premature aging, cancer predisposition, and radiation sensitivity. The gene mutated in AT, ATM (for AT-mutated), had been cloned and found to have ionizing radiation and oxidative stressinducible kinase activity. No treatment can stop the progression of the disease. In this study, the complete open-reading frame of ATM cDNA was cloned into a Herpes simplex virus type-1 (HSV-1) amplicon vector (pTO-ATM), and the transduction of cultured AT cells was demonstrated by immunohistochemistry and Western blot analysis. Functional gene expression was evaluated by cell colony-forming assays following exposure to oxidative stress. The survival of AT cells with ATM gene transduction was about 100% higher compared to nontransduced cells after t-butyl hydroperoxide treatments. Next, the normal ATM gene expression in different regions of the rat brain was studied. Immunohistochemistry staining demonstrated weak endogenous ATM protein expression in neurons of the caudate-putamen, with significantly higher levels of expression detected in neurons in other brain regions. Exogenous ATM gene expression from pTO-ATM after viral transduction in the caudateputamen of the adult rat was examined. At 3 days after injection of the pTO-ATM viral vector, abundant positive ATM staining of the neurons was found at the injection sites, in comparison to the controls. These data demonstrate that the relatively large ATM cDNA can be transduced and expressed in vitro and in vivo from an HSV amplicon viral vector. These data provide initial evidence that the replacement of the ATM gene into the cells of AT patients might be possible some day.

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The herpes simplex virus amplicon: A new eucaryotic defective-virus cloning-amplifying vector

Cited by 496 publications

References 33 publications

Constitutive and Inducible Innate Responses in Cells Infected by HSV-1- Derived Amplicon Vectors

Constitutive and Inducible Innate Responses in Cells Infected by HSV-1- Derived Amplicon Vectors

Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia

Functional expression of ATM gene carried by HSV amplicon vector in vitro and in vivo

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