Replication-defective herpes simplex virus vectors for neurotrophic factor gene transfer in vitro and in vivo

Marconi, Peggy; Simonato, Michele; Zucchini, Silvia; Bregola, Gianni; Argnani, Rafaela; Krisky, David; Glorioso, Joseph C.; Manservigi, Roberto

doi:10.1038/sj.gt.3300882

Cited by 32 publications

(33 citation statements)

References 42 publications

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“…The reporter construct consisted of the lacZ gene upstream from the SV40 polyadenylation signal flanked by PacI restriction sites [30,31]. In the plasmid, the reporter gene, under the control of the herpes ICP0 promoter, was placed within the UL41 coding sequences to allow homologous recombination of the expression cassette into the viral genome.…”

Section: Plasmid and Recombinant Virus Constructionsmentioning

confidence: 99%

“…In this study, we have developed a reliable HSV-derived replication-defective vector [30,31] to efficiently transduce IFI16 into primary human umbilical vein embryo cells (HUVEC), which are usually poorly transfectable by conventional methods. Evaluation of some features of in vitro angiogenesis, namely chemotaxis, Matrigel invasion, tube morphogenesis, and cell cycle progression, has provided for the first time demonstration that the IFN-inducible protein IFI16 impairs the tube morphogenesis and proliferation of human endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

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The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

Ravera

Gioia

Andrea

et al. 2004

Experimental Cell Research

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Immunohistochemical analysis has demonstrated that the human IFI16 gene, in addition to the hematopoietic tissues, is highly expressed in endothelial cells and squamous stratified epithelia. In this study, we have developed a reliable HSV-derived replication-defective vector (TO-IFI16) to efficiently transduce IFI16 into primary human umbilical vein endothelial cells (HUVEC), which are usually poorly transfectable. HUVEC infection with TO-IFI16 virus suppressed endothelial migration, invasion and formation of capillary-like structures in vitro. In parallel, sustained IFI16 expression inhibited HUVEC cell cycle progression, accompanied by significant induction of p53, p21, and hypophosphorylated pRb. Further support for the involvement of these pathways in IFI16 activity came from the finding that infection with TO-IFI16 virus does not impair the in vitro angiogenic activity and cell cycle progression of HUVEC immortalized by HPV16 E6/E7 oncogenes, which are known to inactivate both p53 and pRb systems. This use of a reliable viral system for gene delivery into primary human endothelial cells assigns a potent angiostatic activity to an IFN-inducible gene, namely IFI16, and thus throws further light on antiangiogenic therapy employing IFNs. D

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Section: Plasmid and Recombinant Virus Constructionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

Ravera

Gioia

Andrea

et al. 2004

Experimental Cell Research

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“…It is not unreasonable to predict that nonherpes viral vectors may have similar effects on host cells. For HSV-1, it seems safer to use vectors with multiple deletions of all IE genes 69,70 or virus-free amplicons [71][72][73][74] for gene transfer to nontumoral tissues. For oncolytic viral vectors, it might be plausible to put the IE genes, particularly the ICP0 and 4, under strict cell-type specific control to reduce their expression in normal cells.…”

Section: Hsv-1 Upregulates Telomerase C-t Yang Et Almentioning

confidence: 99%

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Yang

Song

et al. 2003

Gene Ther

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“…18,19,[43][44][45] The full-length ATM cDNA is beyond the packaging capacity of most widely used viral vectors; so we employed an HSV-1-based amplicon vector that, in theory, can package 140 kb of DNA payload. 33,34 The ATM gene, therefore, was cloned into pTO HSV amplicon vector and the insert was confirmed to be intact by Southern blot analysis (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…It is also believed that the HSV helper virus will introduce cytotoxicity to transduced cells. [50][51][52] Using less cytotoxic helper viruses by deletion of more IE genes 45,[53][54][55][56][57][58] or using helper virus-free packaging systems as an attempt to reduce cytotoxicity and immunogenicity [59][60][61][62][63] would be a future solution. No staining in the injection site was observed after PBS was substituted for the primary antibody.…”

Section: Discussionmentioning

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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Replication-defective herpes simplex virus vectors for neurotrophic factor gene transfer in vitro and in vivo

Cited by 32 publications

References 42 publications

The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

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

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