Abstract:
:The clinical success of suicide gene therapy using herpes simplex virus type 1 thymidine kinase (TK) is largely dependent on the capacity of this enzyme to effectively induce the death of bystander cells. We have shown that fusion of TK to an 11-amino acid peptide from the basic domain of the human immunodeficiency virus type 1 Tat protein (Tat11) imparts cell membrane-translocating ability to the enzyme and significantly increases its cytotoxic activity. Here we report on the efficacy of this strategy in two different mouse models of adoptive tumorigenesis, based on the implantation of human Kaposi sarcoma (KS-IMM) cells in nude mice or of B16F10 melanoma cells in syngeneic C57BL/6J mice. Experiments were performed by the subcutaneous injection of mixtures of unmodified tumor cells containing different fractions of TK or Tat11-TK producing cells followed by animal treatment with ganciclovir (GCV). In both systems we consistently found that mice bearing tumors containing Tat11-TK cells displayed significantly retarded tumor growth and prolonged survival as compared with mice inoculated with cells expressing unmodified TK. Collectively, these results demonstrate that fusion of Tat11 to TK imparts remarkable intercellular trafficking capability to the enzyme. This modification of TK might constitute an important step in the optimization of TK suicide gene strategy for gene therapy of cellular proliferation.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Tasciotti E,Giacca Mdoi
10.1089/hum.2005.16.1389keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1389-403issue
12eissn
1043-0342issn
1557-7422journal_volume
16pub_type
杂志文章abstract::Diabetes mellitus derives from either insulin deficiency (type I) or resistance (type II). Homozygous mutations in the insulin receptor (IR) gene cause the rare leprechaunism and Rabson-Mendenhall syndromes, severe forms of hyperinsulinemic insulin resistance for which no therapy is currently available. Systems have b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.1101
更新日期:2004-11-01 00:00:00
abstract::Rat myoblast primary cultures were tested as a model for proinsulin synthesis and processing and unregulated insulin delivery for insulin-dependent diabetes mellitus (IDDM) gene therapy. Three human proinsulin cDNA constructs containing genetically engineered furin endoprotease cleavage sites between the B-chain and C...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.1-71
更新日期:1996-01-01 00:00:00
abstract::We report a novel method for targeting adenovirus-mediated gene delivery. By irradiating mammalian cells prior to adenoviral transduction, adenoviral gene transfer is greatly improved and the adenoviral genome integrates into cellular DNA. In this work, human and rodent cell lines were irradiated and subsequently tran...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.9-1025
更新日期:1997-06-10 00:00:00
abstract::Administration of recombinant adenoviral (AdV) vectors to animals can lead to inflammatory and immune responses. For therapeutic indications in which repeated treatment is necessary, such as cystic fibrosis (CF), these responses can limit the therapeutic usefulness of the vector. In principle, the utility of the vecto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401300042348
更新日期:2001-03-20 00:00:00
abstract::Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. Unfortunately, viruses are limited in their ability to diffuse through tissue. This makes it virtually impossible to infect the majority of tumor cells in vivo and results in inadequate gene transfer. This p...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.8-1209
更新日期:1998-05-20 00:00:00
abstract::We evaluated the efficiency of gene transduction and of gene expression by adenoviral vectors in human lung adenocarcinoma cells. Freshly isolated cancer cells were collected from pleural effusions in adenocarcinoma patients by centrifugation with a Percoll gradient. Adenoviral vectors resulted in effective gene trans...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.1-1
更新日期:1997-01-01 00:00:00
abstract::With the aim of developing new gene transfer tools for treating CF with gene therapy, we have synthesized a novel family of molecules named cationic phosphonolipids. The most efficient among them were selected by in vitro screening to compare their activities in vivo in mouse lungs. We used a reporter gene whose activ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.16-2309
更新日期:1998-11-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017653
更新日期:1999-07-01 00:00:00
abstract::We reported that SNV-derived retroviral vectors, which display single-chain antibodies on the viral surface, enable cell type-specific gene delivery into various human cells. In particular, the SNV cell type-specific gene delivery vector system appears to be well suited to transduce genes into cells of the human hemat...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016663
更新日期:1999-11-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.126
更新日期:2012-02-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.129
更新日期:2009-01-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.229
更新日期:2021-01-22 00:00:00
abstract::Gene therapy studies in primates can provide important information regarding vector tropism, specific cellular expression, biodistribution, and safety prior to clinical trials. In this study, we report the assessment of transduction efficiency of recombinant adeno-associated virus (rAAV) vectors using human postmortem...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.157
更新日期:2011-05-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.111
更新日期:2020-08-01 00:00:00
abstract::Direct arterial gene transfer has been previously achieved using double-balloon catheters and perforated balloons, in most cases facilitated by the use of cationic liposomes or viral vectors. These gene delivery systems, however, have been compromised by issues relating to efficacy and/or safety, and furthermore requi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.6-749
更新日期:1993-12-01 00:00:00
abstract::In vitro delivery of interferon-alpha (IFN-alpha) to cultured human monocytes by means of a replication-incompetent herpesvirus vector inhibits human immunodeficiency virus (HIV) replication. To explore the possibility of IFN-alpha gene delivery by vector-infected human monocytes, monocytes were isolated and the cultu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.11-1331
更新日期:1996-07-10 00:00:00
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journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1089/10430340050016003
更新日期:2000-01-20 00:00:00
abstract::Engineered measles virus (MV) strains deriving from the vaccine lineage represent a promising oncolytic platform and are currently being tested in phase I trials. In this study, we have demonstrated that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor act...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.158
更新日期:2012-04-01 00:00:00
abstract::Low in vivo transduction efficiency and safety concerns have been hurdles for effective hematopoietic stem cell (HSC) gene therapy. Here, we investigate whether the safety and efficiency of retroviral gene transfer into HSCs can be improved by using human allogeneic umbilical cord blood (UCB)-derived supplements inste...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.123
更新日期:2008-07-01 00:00:00
abstract::This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via wee...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2010.020
更新日期:2010-09-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340150504000
更新日期:2001-03-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章,评审
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更新日期:2018-02-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252792567
更新日期:2002-02-10 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017329
更新日期:1999-08-10 00:00:00
abstract::Heme oxygenase 1 (HO-1) is an inducible enzyme that catalyzes heme to generate bilirubin, ferritin, and carbon monoxide. Because enhanced expression of HO-1 confers protection against many types of cell and tissue damage by modulating apoptotic cell death or cytokine expression profiles, we hypothesized that adenoviru...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340260355356
更新日期:2002-11-01 00:00:00
abstract::The first report of in vivo gene delivery to the retina dates back to 1987 when a retroviral vector was injected intraocularly in newborn mice. Later came the observation that retinal cells could be successfully transduced using adenoviral and then adeno-associated and lentiviral vectors. By 2000, it had become clear ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.164
更新日期:2017-11-01 00:00:00
abstract::Foamy virus (FV) vectors are a promising gene delivery system for use in hematopoietic stem cell gene therapy. Previous FV vector marking studies in the NOD/SCID xenotransplantation model used umbilical cord blood (UCB)-derived SCID repopulating cells (SRCs) that were assayed 5-10 weeks posttransplantation. We now rep...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340460732481
更新日期:2004-01-01 00:00:00
abstract::Retrovirus integration into the host cell genome occurs most efficiently in replicating cells. In agreement with this notion, it was observed that the efficiency with which hemopoietic stem cells (HSC) can be transduced is greatly enhanced when the hemopoietic growth factor (HGF) interleukin 3 (IL-3) is added to co-cu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1991.2.4-301
更新日期:1991-01-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.2-207
更新日期:1998-01-20 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.17-2011
更新日期:1997-11-20 00:00:00