Abstract:
:The possibility of achieving multiple systemic expression of human interferon-beta in mice upon repeated intravenous administration of cationic liposome-DNA complex (lipoplex) was investigated. Lipoplexes containing the pentammonio lipid pcTG90 were first optimized by selecting the most efficient ratio of pcTG90 to phosphatidylethanolamine (DOPE) and the N/P ratio of cationic lipid nitrogen to DNA phosphate. Highest levels and reproducibility of gene expression were obtained using pcTG90/DOPE (1:2) liposomes complexed with the IFNB1 gene containing plasmid pTG14169 at a N/P ratio of 10. Following lipoplex administration, an early but transient human interferon-beta expression in serum was observed. Importantly, repeated systemic gene expression could be achieved upon re-administration with a minimal time interval of 14 days between two injections. For an interval period of 6 days, subsequent gene expression was inhibited by a first administration of lipoplexes containing either a luciferase reporter gene plasmid or an empty plasmid, but was not inhibited when free (non-complexed) plasmid pTG14169 was first injected. Multiple injections of pcTG90-lipoplex performed once every other month resulted in three subsequent peaks of systemic IFNB1 gene expression in mice. In conclusion, our study demonstrates the feasibility of expanding the therapeutic window of a cytokine using repetitive intravenous administration of lipoplex.
journal_name
Gene Therjournal_title
Gene therapyauthors
Meyer O,Schughart K,Pavirani A,Kolbe HVdoi
10.1038/sj.gt.3301289keywords:
subject
Has Abstractpub_date
2000-09-01 00:00:00pages
1606-11issue
18eissn
0969-7128issn
1476-5462journal_volume
7pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Nonhealing bone defects are difficult to treat. As the bone morphogenic protein and transforming growth factor beta pathways have been implicated in bone healing, we hypothesized that percutaneous Smad7 silencing would enhance signaling through both pathways and improve bone formation. Critical sized parietal trephine...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.15
更新日期:2013-09-01 00:00:00
abstract::We explored the possibility of using a genetic approach to inhibit integrin-mediated endothelial cell adhesion and survival. We constructed recombinant adenoviruses (Ads) expressing chimeric proteins consisting of the cytoplasmic and transmembrane domains of integrin beta1 (CH1), beta3 (CH3) or the beta1 transmembrane...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301236
更新日期:2000-08-01 00:00:00
abstract::Newly isolated serotypes of AAV readily cross the endothelial barrier to provide efficient transgene delivery throughout the body. However, tissue-specific expression is preferred in most experimental studies and gene therapy protocols. Previous efforts to restrict gene expression to the myocardium often relied on dir...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.105
更新日期:2011-01-01 00:00:00
abstract::RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and unifor...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302846
更新日期:2007-01-01 00:00:00
abstract::First-generation adenoviral (Ad) vectors are frequently used vectors for experimental and clinical gene transfer. Earlier it has been shown that parallel overexpression of the cell cycle regulator p21(Waf1/Cip1) (p21) or antiapoptotic bcl-2 from a second vector reduces cytotoxicity and improves transgene expression. H...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.2
更新日期:2009-04-01 00:00:00
abstract::Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA hu...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301274
更新日期:2000-09-01 00:00:00
abstract::In order to characterize protein targeting signals in polarized postmitotic cortical neurones in vitro, we have developed recombinant and amplicon type vectors derived from herpes simplex virus 1 (HSV1) to transfer genes into these cells. We examined the targeting of both bacterial proteins, which lack specific target...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Cationic lipid-DNA complexes (lipoplexes) have been widely used as gene transfer vectors which avoid the adverse immunogenicity and potential for viraemia of viral vectors. With the long-term aim of gene transfer into skeletal muscle in vivo, we describe a direct in vitro comparison of two commercially available catio...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300604
更新日期:1998-04-01 00:00:00
abstract::Gene therapy with Plasmid AMEP (antiangiogenic metargidin peptide) has recently been studied as a potential targeted therapy for melanoma. This plasmid is designed to downregulate α5β1 and αvβ3 integrins. In our study, electroporation was used as a nonviral delivery system. We investigated the antiangiogenic and direc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.26
更新日期:2015-07-01 00:00:00
abstract::To facilitate the understanding of the complex process of target gene expression and its control, we report a modified inducible system for activation or repression of target gene expression in response to an exogenously administered compound. The main component of this inducible system is a chimeric transcriptional a...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300402
更新日期:1997-05-01 00:00:00
abstract::We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate marke...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300565
更新日期:1998-01-01 00:00:00
abstract::Earlier this laboratory constructed a herpes simplex virus 1 recombinant (R5111) that carries a IL13 ligand inserted into glycoprotein D and can enter cells via the IL13Ralpha2 receptor commonly expressed on the surface of malignant glioma cells. In this report, we describe the properties of two recombinant viruses ca...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302685
更新日期:2006-04-01 00:00:00
abstract::Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth f...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.153
更新日期:2010-03-01 00:00:00
abstract::Advanced prostate cancer (PC) still remains incurable. Novel immunogene therapy shows promise as treatment strategy that can target both localized and metastasized PC. In this study, we have developed a PC-specific oncolytic adenovirus (Ad-PL-PPT-E1A) armed with fusion gene of prostate-specific antigen and CD40 ligand...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.46
更新日期:2014-08-01 00:00:00
abstract::Autonomous parvoviruses are small, single strand DNA viruses which preferentially replicate in transformed and tumor cells, causing cell death by expression of the cytotoxic nonstructural protein, NS1. Several parvoviruses of the rodent group, including LuIII, efficiently infect human transformed cell lines. The poten...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300832
更新日期:1999-03-01 00:00:00
abstract::Ideal methods for human gene therapy will eventually include direct gene transfer to defective tissues in a patient in vivo. Toward that goal, we have used high titer, pseudotyped retroviral vectors expressing genes for the Escherichia coli beta-galactosidase (lacZ) or hepatitis B virus surface antigen (HBsAg) to infe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Efficient gene delivery is a critical obstacle for gene therapy that must be overcome. Until current limits of gene delivery technology are solved, identification of systems with bystander effects is highly desirable. As an anticancer agent, radioactive iodine (131)I has minimal toxicity. The physical characteristics ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302758
更新日期:2006-07-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscular disorder caused by a defect in the DMD gene. AAV vector-mediated micro-dystrophin cDNA transfer is an attractive approach to treatment of DMD. To establish effective gene transfer into skeletal muscle, we examined the transduction efficiency of an AAV v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301829
更新日期:2002-12-01 00:00:00
abstract::HaCaT cells, a spontaneously immortalised, nontumorigenic keratinocyte line, were used as a more amenable model than primary keratinocytes for ex vivo-mediated gene transfer. These cells were transduced with retroviral vectors containing the factor IX cDNA under the control of a cytomegaloviral (CMV) promoter/enhancer...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300591
更新日期:1998-03-01 00:00:00
abstract::Although particle-mediated gene transfer using gene gun technology has been applied for gene transfer into epidermis, applications of this technology to visceral tissues have not been well investigated. Although all helium gas-driven gene gun instruments have used macrocarriers to discharge DNA-coated microprojectiles...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301192
更新日期:2000-07-01 00:00:00
abstract::This study was designed to determine whether Coxsackie adenovirus receptor (CAR) and alpha nu beta3/alpha nu beta5 integrin co-receptors are involved in adenovirus gene transfer in the rat cochlea. We find that CAR and integrin co-receptors are expressed in every cell subtype transduced by the adenoviral vector Ad5 De...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302826
更新日期:2007-01-01 00:00:00
abstract::The structure of 'stabilized plasmid-lipid particles' (SPLP) and their properties as systemic gene therapy vectors has been investigated. We show that SPLP can be visualized employing cryo-electron microscopy to be homogeneous particles of diameter 72 +/- 5 nm consisting of a lipid bilayer surrounding a core of plasmi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301308
更新日期:2000-11-01 00:00:00
abstract::Chimeric antigen receptors (CARs, immunoreceptors) are frequently used to redirect T cells with pre-defined specificity, in particular towards tumour cells for use in adoptive immunotherapy of malignant diseases. Specific targeting is mediated by an extracellularly located antibody-derived binding domain, which is joi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.91
更新日期:2010-10-01 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::Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. We have devised a novel way of using magnetic nanoparticles (MNPs) to enh...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.57
更新日期:2008-06-01 00:00:00
abstract::This study was designed to evaluate the utility of positron emission tomography (PET) to quantify the magnitude and spatial distribution of transgene expression after different methods of adenoviral vector delivery (with surfactant- and saline-based vehicles) within rat lungs. In all, 17 animals (eight in the surfacta...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302117
更新日期:2003-12-01 00:00:00
abstract::Persistence of human immunodeficiency virus (HIV) despite highly active antiretroviral therapy (HAART) is a lasting challenge to virus eradication. To develop a strategy complementary to HAART, we constructed a series of Rev-dependent lentiviral vectors carrying diphtheria toxin A chain (DT-A) and its attenuated mutan...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.53
更新日期:2010-09-01 00:00:00
abstract::Naturally occurring drug resistance genes of human origin can be exploited for selection of genetically engineered cells co-expressing a desired therapeutic transgene. Their non-immunogenicity in clinical applications would be a major asset. Human cytidine deaminase (hCD) is a chemoresistance gene that inactivates cyt...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301675
更新日期:2002-04-01 00:00:00
abstract::Advances in genetic analysis and a greater understanding of human immunodeficiency virus (HIV) molecular pathogenesis have identified critical viral targets for gene interference strategies. RNase P molecules have been proposed as a novel approach for gene targeting based upon their potent catalytic activity, as well ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301606
更新日期:2001-12-01 00:00:00
abstract::Active disease of tuberculosis (TB) can be developed decades later by either a relapse of the initial infection (endogenous reactivation) or by an entrance of the secondary infection (exogenous reinfection), since the current chemotherapy cannot lead to complete elimination of tuberculosis. Although the immunotherapeu...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302465
更新日期:2005-04-01 00:00:00