Abstract:
:Replicating viruses for cancer gene therapy have beneficial antitumor effects, however, in the setting of an enzyme/prodrug system, the interactions between these viruses and the activated agents are complex. A replicating vaccinia virus expressing the cytosine deaminase gene (VVCD), which converts the prodrug 5-FC into 5-FU, was characterized in vitro and in vivo for its antitumor effects and pathogenicity. Replicating VVCD (+/-5-FC) at various MOIs was used to infect MC38 murine colon adenocarcinoma cells. At high MOIs (>0.1) virus alone was able to kill the majority (65-90%) of cells by day 5 with no additional benefit from prodrug. At low MOIs only the effect of prodrug is seen. Cell lysates demonstrated 300-fold reduced viral recovery from cells treated with both VVCD and 5-FC compared with controls treated with virus alone. Nude mice bearing subcutaneous MC38 tumors were injected with VVCD (or control) and treated with 5FC or control. Mice injected with VVCD (with or without 5FC treatment) had smaller tumors than the controls, suggesting that replicating vaccinia alone is cytotoxic to tumors in vivo. The addition of 5-FC improved the antitumor response when a low dose of virus was injected into tumors. Also, compared with mice that received virus alone, those that received VVCD and 5FC had significantly prolonged survival from virus-mediated death. In conclusion, the addition of an enzyme/prodrug system to a replicating virus can improve the antitumor response and decrease viral pathogenicity. Gene Therapy (2000) 7, 1217-1223.
journal_name
Gene Therjournal_title
Gene therapyauthors
McCart JA,Puhlmann M,Lee J,Hu Y,Libutti SK,Alexander HR,Bartlett DLdoi
10.1038/sj.gt.3301237keywords:
subject
Has Abstractpub_date
2000-07-01 00:00:00pages
1217-23issue
14eissn
0969-7128issn
1476-5462journal_volume
7pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::The majority of immunotherapy-based gene therapy protocols consist of ex vivo gene transfer in tumor cells. To prevent further in vivo growth, modified cells must be irradiated before reinjection into patients. The present study examines the effects of gamma-irradiation on transgene expression in transduced leukemic c...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301870
更新日期:2003-02-01 00:00:00
abstract::Regulated gene delivery systems are usually made of two elements: an inducible promoter and a transactivator. In order to optimize gene delivery and regulation, a single viral vector ensuring adequate stoichiometry of the two elements is required. However, efficient regulation is hampered by interferences between the ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301838
更新日期:2003-01-01 00:00:00
abstract::A recombinant adeno-associated virus (rAAV) vector was used to overexpress the anti-apoptotic Bcl-2-family protein, BCL-w, in rat brain. Three weeks after injecting the vector into cerebral cortex and striatum on one side, temporary focal ischemia was induced by occlusion of the ipsilateral middle cerebral artery for ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301868
更新日期:2003-01-01 00:00:00
abstract::VP22, a structural protein from herpes simplex virus type I, exhibits the unique property of intercellular trafficking. This protein is exported from primary expressing cells and subsequently imported into neighbouring cells. This property is conserved when VP22 is genetically fused to a protein, making it a promising...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301904
更新日期:2003-02-01 00:00:00
abstract::There is growing interest in gene delivery to the eye in order to develop gene therapy for the many ocular disorders which may be amenable to this approach. To date, recombinant adenoviruses (AV) have been the main vector used for gene delivery to anterior and posterior segments in animal models. As with delivery to o...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300761
更新日期:1998-11-01 00:00:00
abstract::Radiosensitization of human gastrointestinal tumors by 5-fluorouracil (5-FU) has been studied in vitro and clinically in human cancer therapy trials. The bacterial enzyme cytosine deaminase (CD) converts the nontoxic prodrug 5-fluorocytosine (5-FC) into 5-FU. Human colon cancer cells stably expressing CD have been sho...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301196
更新日期:2000-06-01 00:00:00
abstract::Regulated expression of therapeutic genes is required for long-term gene therapy applications for many disorders. Here we describe a doxycycline (dox)-regulated lentiviral vector system consisting of two HIV-1-based self-inactivating viruses. One of the vectors is constitutively expressing a novel improved version of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301889
更新日期:2003-03-01 00:00:00
abstract::Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301636
更新日期:2002-02-01 00:00:00
abstract::Cell transplantation holds promise as a potential treatment for cardiac dysfunction. Our group has isolated populations of murine skeletal muscle-derived stem cells (MDSCs) that exhibit stem cell-like properties. Here, we investigated the fate of MDSCs after transplantation into the hearts of dystrophin-deficient mdx ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302521
更新日期:2005-08-01 00:00:00
abstract::Human immunodeficiency virus (HIV) infection ultimately leads to the destruction of the CD4+ lymphocyte subset and the onset of AIDS. In recent years, several gene therapy procedures making use of retroviral vectors that selectively target HIV susceptible cells have been proposed in order to interfere with HIV product...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300646
更新日期:1998-05-01 00:00:00
abstract::Defects of the mitochondrial genome cause a wide variety of clinical disorders. Except for rare cases where surgery or transplant is indicated, there is no effective treatment for patients. Genetic-based therapies are consequently being considered. On account of the difficulties associated with mitochondrial (mt) tran...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2008.91
更新日期:2008-07-01 00:00:00
abstract::Over the last years, RNA interference (RNAi) has become a widely used technique that permits the knock-down, and hence functional analysis, of individual genes in vertebrate cells. However, the high failure rate of the RNA molecules used in RNAi experiments continues to be a problem. In this paper, I describe a set of...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302656
更新日期:2006-03-01 00:00:00
abstract::The efficiency of plasmid gene transfer to skeletal muscle can be significantly improved by the application of an electrical field to the muscle following injection of plasmid DNA. However, this electrotransfer is associated with significant muscle damage which may result in substantial loss of transfected muscle fibr...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301522
更新日期:2001-08-01 00:00:00
abstract::Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS), where suspected autoimmune attack causes nerve demyelination and progressive neurodegeneration and should benefit from both anti-inflammatory and neuroprotective strategies. Although neuroprotection strategies are relatively une...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302025
更新日期:2003-05-01 00:00:00
abstract::The clinical efficacy and safety as well as the application range of gene therapy will be broadened by developing systems capable of finely modulating the expression of therapeutic genes. Transgene regulation will be crucial for maintaining appropriate levels of a gene product within the therapeutic range, thus preven...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302251
更新日期:2004-04-01 00:00:00
abstract::Adenovirus (Ad) vectors are of utility for many therapeutic applications. Strategies have been developed to alter adenoviral tropism to achieve a cell-specific gene delivery capacity employing fiber modifications allowing genetic incorporation of targeting motifs. In this regard, single chain antibodies (scFv) represe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302603
更新日期:2006-01-01 00:00:00
abstract::Gene transfer complexes containing poly-L-lysine (poly-K) and DNA with ligands directed at the serpin enzyme complex receptor (sec-R) deliver reporter genes to receptor-bearing cells in vivo. Expression lasts for about 30 days, when complexes containing long-chain poly-K are used. Extending the duration of expression ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302299
更新日期:2004-09-01 00:00:00
abstract::To induce RNA interference (RNAi), either small interfering RNAs (siRNAs) are directly introduced into the cell or short hairpin RNAs (shRNAs) are expressed from a DNA vector. At present, shRNAs are commonly synthesized by RNA polymerase III (Pol III) promoters of the H1 and U6 RNAs. In this study, we designed and cha...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303055
更新日期:2008-02-01 00:00:00
abstract::Adenovirus (Ad)-mediated delivery of anti-angiogenic molecules into tumors constitutes an appealing approach for growth inhibition. However, lack of expression on tumors of Ad receptors leads to weak tumor transduction. Therefore, to provide Ad with a new entry pathway into tumors, an NGR peptide was inserted into eit...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.97
更新日期:2009-12-01 00:00:00
abstract::p53 gene therapy is being tested clinically for the treatment of human cancer, however, some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via a...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301538
更新日期:2001-09-01 00:00:00
abstract::Parkinson's disease is a prevalent progressive degenerative disorder of the elderly. There is a current need for novel therapeutic strategies because the standard levodopa pharmacotherapy is only temporarily efficacious. Recently, there have been some high-profile successful preclinical results obtained in animal mode...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302669
更新日期:2006-03-01 00:00:00
abstract::Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with diverse disorders and characterized by disruption of the alveolar-capillary barrier, leakage of edema fluid into the lung, and substantial inflammation leading to acute respiratory failure. Gene therapy is a potentially powerful...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.19
更新日期:2016-06-01 00:00:00
abstract::Reactive oxygen species (ROS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), while antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD) and catalase, block radical-induced events. The present study tested if the ex vivo transfer of EC-SOD and catalase genes alone or in combi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301916
更新日期:2003-04-01 00:00:00
abstract::Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis of mammalian cells. The use of DNA-based plasmid vectors to achieve transient and stable expression of siRNA has been developed to avoid the problems of double-stranded oligonucleotides transfection...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302878
更新日期:2007-03-01 00:00:00
abstract::Highly active antiretroviral therapy (HAART) treatment for HIV has changed the course of AIDS in societies in which the drugs are readily available. Despite the great success of HAART, drug resistance and toxicity issues still remain a concern for some individuals. Thus, a number of investigators have been exploring o...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2011.149
更新日期:2011-12-01 00:00:00
abstract::We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation in vivo. In the present study, we employed decoy ODN targeting the transcription factor nu...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301478
更新日期:2001-06-01 00:00:00
abstract::Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates blood glucose level post-prandially. It has been proposed that GLP-1 can be used in type 2 diabetes (T2D) mellitus treatment because of its insulinotropic action. Despite its remarkable advantages, GLP-1 suffers the disadvantage of an extremely shor...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.25
更新日期:2011-08-01 00:00:00
abstract::Current experimental gene therapy approaches for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) include the use of viral vectors expressing antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes. However, since increasing evidence favors a role for alpha-synuclein accumulation in the p...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302349
更新日期:2004-12-01 00:00:00
abstract::Sustainable correction of severe human genetic disorders of self-renewing tissues, such as the blistering skin disease junctional epidermolysis bullosa (JEB), is facilitated by stable genomic integration of therapeutic genes into somatic tissue stem cells. While integrating viral vectors can achieve this, they suffer ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301978
更新日期:2003-07-01 00:00:00
abstract::Dendritic cell (DC)-based vaccine approaches are being actively evaluated for developing immunotherapeutic agents against cancers. In this study, we investigated the use of engineered DCs expressing transgenic tumor-associated antigen hgp100 and the regulatory cytokine interleukin-21, namely DC-hgp100/mIL-21, as a the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.12
更新日期:2014-05-01 00:00:00