Deletion of multiple immediate–early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons

Krisky, David; Wolfe, Darren; Goins, William F.; Marconi, Peggy; Ramakrishnan, Ramesh; Mata, Marina; Rouse, Richard; Fink, David J.; Glorioso, Joseph C.

doi:10.1038/sj.gt.3300766

Cited by 221 publications

(169 citation statements)

References 10 publications

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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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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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“…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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Section: Recombinant Virusesmentioning

confidence: 99%

“…18 Briefly, all [18][19][20][21][22] which allowed for extended transgene expression. 18,19,22 Vector cytotoxicity Cell viability assays were performed to assess the toxicity of viral mutants deleted for one or three IE genes. Rat gliosarcoma 9L cells which are highly susceptible to infection with replication-incompetent ICP4 − HSV-1 mutants 18 were infected with the single or triple IE gene deletion viruses SOZ.1, T.1 and TOZ.1 at multiplicities of infection (MOIs) of 0.1, 1 and 10.…”

Section: Recombinant Virusesmentioning

confidence: 99%

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HSV vector cytotoxicity is inversely correlated with effective TK/GCV suicide gene therapy of rat gliosarcoma

et al. 2000

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Deletion of multiple immediate–early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons

Cited by 221 publications

References 10 publications

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

HSV vector cytotoxicity is inversely correlated with effective TK/GCV suicide gene therapy of rat gliosarcoma

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