Abstract:
:Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats with hemagglutinating virus of Japan-envelope (HVJ-E) vectors containing Epstein-Barr virus (EBV) plasmids encoding the genes for insulin and the GLUT 2 transporter. Efficient delivery of the genes was achieved with the HVJ-E vector, and the use of the EBV replicon vector led to prolonged hepatic gene expression. Blood glucose levels were normalized for at least 3 weeks as a result of the gene therapy. Cotransfection of GLUT 2 with insulin permitted the diabetic rats to regulate their blood glucose levels upon exogenous glucose loading in a physiologically appropriate manner and improved postprandial glucose levels. Moreover, cotransfection with insulin and GLUT 2 genes led to in vitro glucose-stimulated insulin secretion that involved the closure of K(ATP) channels. The present study represents a new way to efficiently deliver insulin gene in vivo that is regulated by ambient glucose level with prolonged gene expression. This may provide a basis to overcome limitations of insulin gene therapy in humans.
journal_name
Gene Therjournal_title
Gene therapyauthors
Kim YD,Park KG,Morishita R,Kaneda Y,Kim SY,Song DK,Kim HS,Nam CW,Lee HC,Lee KU,Park JY,Kim BW,Kim JG,Lee IKdoi
10.1038/sj.gt.3302644subject
Has Abstractpub_date
2006-02-01 00:00:00pages
216-24issue
3eissn
0969-7128issn
1476-5462pii
3302644journal_volume
13pub_type
杂志文章相关文献
GENE THERAPY文献大全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::Aptamers are oligonucleotides evolved in vitro or in nature to bind target ligands with high affinity and specificity. They are emerging as powerful tools in the fields of therapeutics, drug development, target validation and diagnostics. Aptamers are attractive alternatives to antibody- and small-molecule-based thera...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302900
更新日期:2007-02-01 00:00:00
abstract::The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this re...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the treatment of neurodegenerative diseases. While AAVs are generally administered systemically to newborns in preclinical studies of neurological disorders, in adults the maturity of the blood-brain barrier (BBB) must be considered when selecti...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2017.18
更新日期:2017-05-01 00:00:00
abstract::The CMV promoter drives high transgene expression and is one of the most commonly used promoters for gene transfer. Tissue-specific mammalian promoters provide an alternative, and it would be useful to have a system to directly compare them to viral promoters free from potential confounding vector-related effects. In ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302700
更新日期:2006-05-01 00:00:00
abstract::Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the target...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.48
更新日期:2016-10-01 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::Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was p...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.16
更新日期:2010-06-01 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::Short hairpin RNA (shRNA)-mediated gene regulation is a commonly used technique for gene manipulation. An efficient and safe delivery system is indispensable when shRNA is delivered into living organisms for gene therapy. Previous studies have proved that DNA and protein can be delivered into dendritic cells (DCs) by ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.50
更新日期:2014-07-01 00:00:00
abstract::We report on long-term delivery of an interferon-gamma (IFN gamma) inhibitory protein by intramuscular (i.m.) gene therapy. IFN gamma is a cytokine that plays an important role in many inflammatory disorders, including autoimmune insulin-dependent diabetes mellitus (IDDM) in NOD mice and (in various strains) multiple ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300879
更新日期:1999-05-01 00:00:00
abstract::Human adenovirus (Ad) vectors are extensively used as gene transfer vehicles. However, a serious obstacle for the use of these vectors in clinical applications is due to pre-existing immunity to human Ads affecting the efficacy of gene transfer. One of the approaches to circumvent host immune response could be the dev...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302146
更新日期:2004-01-01 00:00:00
abstract::To identify the intracellular barriers to efficient gene transfer, we studied the intracellular trafficking of biotinylated plasmid DNA complexed with either fluorescein-conjugated lactosylated or mannosylated polylysine by confocal microscopy. Both are known to be taken up by cystic fibrosis airway epithelial cells (...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301768
更新日期:2002-08-01 00:00:00
abstract::Polyethylenimine (PEI) has been studied as an efficient nonviral gene transfer vector. Here, we report the biodistribution fates and safety of plasmid DNA intravenously administered in PEI complexes. Using pCMVbeta as a model gene, the biodistribution of plasmid DNA was measured by quantitative polymerase chain reacti...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301516
更新日期:2001-10-01 00:00:00
abstract::Angiogenesis plays a pivotal role in tumor growth, tissue invasion and metastasis. Endostatin is an angiogenesis inhibitor and has been shown to reduce tumor growth in animal models. However, therapy with recombinant endostatin protein was hampered by its short half-life and very-low yield of bioactive protein. We per...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303038
更新日期:2008-02-01 00:00:00
abstract::Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for t...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301348
更新日期:2001-01-01 00:00:00
abstract::A novel class of cationic hyperbranched polymers, containing branched oligoethylenimine (OEI 800 Da) as core, diacrylate esters as linkers and oligoamines as surface modification, was synthesized and evaluated regarding their structure-activity relationship as gene carriers. We show that pseudodendritic core character...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303046
更新日期:2008-01-01 00:00:00
abstract::The bystander effect (BSE) is an interesting and important property of the herpes thymidine kinase/ganciclovir (hTK/GCV) system of gene therapy for cancer. With the BSE, not only are the hTK expressing cells killed upon ganciclovir (GCV) exposure but also neighboring wild-type tumor cells. On testing a large number of...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300784
更新日期:1998-12-01 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::Gene therapy with viral vectors has progressed to clinical trials. However, the localization of viral vector delivery to diseased target sites remains a challenge. We tested the hypothesis that an adenoviral vector could be successfully delivered by complexation with a specific antibody that is bound to a biodegradabl...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301452
更新日期:2001-05-01 00:00:00
abstract::Viral therapy of cancer includes strategies such as viral transduction of tumour cells with 'suicide genes', using viral infection to trigger immune-mediated tumour cell death and using oncolytic viruses for their direct anti-tumour action. However, problems still remain in terms of adequate viral delivery to tumours....
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2010.48
更新日期:2010-08-01 00:00:00
abstract::Introducing exogenous genes into cells is one of the most important molecular techniques to study gene functions. Comparing to other type of cells, neurons are more difficult to transfect with cDNAs because they are very sensitive to microenvironmental changes. Among various gene transfer techniques, the Ca(2+)-phosph...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302305
更新日期:2004-09-01 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::For many gene therapy applications the effective titre of retroviral vectors is a limiting factor both in vitro and in vivo. Purification and concentration of retrovirus from packaging cell supernatant can overcome this problem. To this end we have investigated a novel procedure which involves complexing retrovirus to...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301201
更新日期:2000-06-01 00:00:00
abstract::This study uses a novel approach to gene therapy in which plasmid DNA is targeted to the pancreas in vivo using ultrasound-targeted microbubble destruction (UTMD) to achieve islet regeneration. Intravenous microbubbles carrying plasmids are destroyed within the pancreatic microcirculation by ultrasound, achieving loca...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.85
更新日期:2010-11-01 00:00:00
abstract::Patients frequently experience a loss of salivary function following irradiation (IR) for the treatment of an oral cavity and oropharyngeal cancer. Herein, we tested if transfer of fibroblast growth factor-2 (FGF2) cDNA could limit salivary dysfunction after fractionated IR (7.5 or 9 Gy for 5 consecutive days to one p...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.63
更新日期:2014-10-01 00:00:00
abstract::Plasmids carrying the Epstein-Barr virus (EBV) latent gene EBNA1 and the EBV latent origin of replication (oriP) stay in transfected human cells as autonomously replicating extrachromosomal genetic units. They thus might represent a suitable tool for cytokine gene introduction into human tumor cells with the prospect ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300363
更新日期:1997-02-01 00:00:00
abstract::Intracardiac gene transfer and gene therapy have been investigated with different vector systems. Here we used adeno-associated virus (AAV) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden Syrian hamsters. The method of gene delivery was direct infusion of the AAV2 vectors into ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302078
更新日期:2003-10-01 00:00:00
abstract::We introduce an injectable system for the formation of a biodegradable DNA-containing implant that releases DNA over a 2-month period to provide a robust and prolonged gene expression at the site. Sustained delivery of the appropriate plasmid DNA resulted in sustained expression of luciferase, the persistent appearanc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301786
更新日期:2002-09-01 00:00:00
abstract::Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) promotes soft tissue and bone healing, and is Food and Drug Administration-approved for treatment of diabetic ulcers and periodontal defects. The short half-life of topical rhPDGF-BB protein application necessitates bolus, high-dose delivery. Gene therapy...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.73
更新日期:2017-01-01 00:00:00