Ribonucleotide Reductase Encoded by Herpes Simplex Virus Is a Determinant of the Pathogenicity of the Virus in Mice and a Valid Antiviral Target

Jm, Cameron; McDougall, Iris M.; Hs, Marsden; Vg, Preston; Dm, Ryan; Jh, Subak-Sharpe

doi:10.1099/0022-1317-69-10-2607

Cited by 143 publications

(70 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a disseminated brain tumor model, intrathecal inoculation of hrR3 was found to cause marked neurologic morbidity and vector-related mortality. 43 HSV ribonucleotide reductase mutants (ICP6 − ) have greatly reduced pathogenicity in adult mice, 44,45 however, they do form productive lesions in guinea pigs and significant virulence in newborn mice. 45,46 In previous studies, promoter elements inserted into the HSV-1 genome were affected by the regulatory properties of surrounding HSV-1 sequences.…”

Section: Discussionmentioning

confidence: 99%

Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo

Tani

Feigenbaum

et al. 1999

Gene Ther

View full text Add to dashboard Cite

Targeting viral vectors to appropriate cell types so that norexpressing tumor cell lines, while all cell lines were equally mal cells are not adversely affected is an important goal susceptible to a tissue nonspecific HSV recombinant, hrR3. for gene therapy. Previously, we described a novelIn vivo, G92A replicated well in subcutaneous xenografts approach to viral gene therapy using a conditional, repliof human hepatoma cells (Hep3B) in athymic mice, but not cation-competent herpes simplex virus (HSV), where repliin non-hepatoma subcutaneous tumors (PC3 and HeLa), cation and associated cytotoxicity are limited to a specific whereas, hrR3 replicated well in both tumor types. Intratucell-type by the regulated expression of an essential moral inoculation of G92A inhibited the growth of estabimmediate-early viral gene product. In this report we analished subcutaneous hepatoma tumors in nude mice, but lyze the hepatoma-specific replication, cytotoxicity and not prostate tumors. Replication-competent viral vectors anti-tumor effect of recombinant HSV G92A, regulated by controlled by cell-specific transcriptional regulatory the albumin enhancer/promoter. G92A efficiently replicated sequences provide a new therapeutic strategy for tumor in vitro in two human hepatoma cell lines expressing albutherapy. min, but not in four human non-hepatoma, albumin-non-

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo

Tani

Feigenbaum

et al. 1999

Gene Ther

View full text Add to dashboard Cite

show abstract

“…Activity of RR is required for efficient viral DNA replication. 136,137 The U L 39-deleted virus, hrR3, is significantly attenuated for replication in normal cells but replicates efficiently in malignant cells. [138][139][140] This virus has demonstrated selective replication in malignant tissues and has produced substantial antineoplastic effects and survival benefit in animal models of the brain, 138,141,142 pancreas, 143 colon 144 and liver cancers.…”

Section: Single Gene Deletionmentioning

confidence: 99%

Herpes simplex virus 1 (HSV-1) for cancer treatment

2006

View full text Add to dashboard Cite

Cancer remains a serious threat to human health, causing over 500 000 deaths each year in US alone, exceeded only by heart diseases. Many new technologies are being developed to fight cancer, among which are gene therapies and oncolytic virotherapies. Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus with many favorable properties both as a delivery vector for cancer therapeutic genes and as a backbone for oncolytic viruses. Herpes simplex virus type 1 is highly infectious, so HSV-1 vectors are efficient vehicles for the delivery of exogenous genetic materials to cells. The inherent cytotoxicity of this virus, if harnessed and made to be selective by genetic manipulations, makes this virus a good candidate for developing viral oncolytic approach. Furthermore, its large genome size, ability to infect cells with a high degree of efficiency, and the presence of an inherent replication controlling mechanism, the thymidine kinase gene, add to its potential capabilities. This review briefly summarizes the biology of HSV-1, examines various strategies that have been used to genetically modify the virus, and discusses preclinical as well as clinical results of the HSV-1-derived vectors in cancer treatment.

show abstract

“…Genetic alterations in the thymidine kinase gene (TK), 55 ribonucleotide reductase ICP6/RR and/or ICP34.5/γ34.5, for example, restrict viral replication to rapidly dividing cells 11,59,85 and create safer oncolytic viruses. 45,70 This modification prevents viral replication in normal brain tissue, preventing lifethreatening encephalitis.…”

Section: Gene Therapy For Brain Tumorsmentioning

confidence: 99%

Current standing and frontiers of gene therapy for meningiomas

Ramos

Flores-Rodríguez

Martínez-Gutiérrez

et al. 2013

FOC

View full text Add to dashboard Cite

Meningiomas are among the most common intracranial tumors. The treatment of choice for these lesions is complete resection, but in 50% of cases it is not achieved due to tumor location and/or surgical morbidities. Moreover, benign meningiomas have high recurrence rates of up to 32% in long-term follow-up. Molecular analyses have begun to uncover the genetics behind meningiomas, giving rise to potential genetics-based treatments, including gene therapy. The authors performed a literature review on the most relevant genes associated with meningiomas and both current and potential gene therapy strategies to treat these tumors. Wild-type NF2 gene insertion, oncolytic viruses, and transfer of silencing RNA have all shown promising results both in vitro and in mice. These strategies have decreased meningioma cell growth, proliferation, and angiogenesis. However, no clinical trial has been done to date. Future research and trials in gene insertion, selective inhibition of oncogenes, and the use of oncolytic viruses, among other potential treatment approaches, may shape the future of meningioma management.

show abstract

Ribonucleotide Reductase Encoded by Herpes Simplex Virus Is a Determinant of the Pathogenicity of the Virus in Mice and a Valid Antiviral Target

Cited by 143 publications

References 27 publications

Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo

Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo

Herpes simplex virus 1 (HSV-1) for cancer treatment

Current standing and frontiers of gene therapy for meningiomas

Contact Info

Product

Resources

About