Abstract:
:Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 (Ex4) have displayed potent glucose homeostasis-modulating characteristics in type 2 diabetes (T2D). However, there are few reports of effectiveness in type 1 diabetes (T1D) therapy, where there is massive loss of beta cells. We previously described a novel GLP-1 analogue consisting of the fusion of active GLP-1 and IgG heavy chain constant regions (GLP-1/IgG-Fc), and showed that in vivo expression of the protein, via electroporation-enhanced intramuscular plasmid-based gene transfer, normalized blood glucose levels in T2D-prone db/db mice. In the present study, GLP-1/IgG-Fc and Ex4/IgG-Fc were independently tested in multiple low-dose streptozotocin-induced T1D. Both GLP-1/IgG-Fc and Ex4/IgG-Fc effectively reduced fed blood glucose levels in treated mice and ameliorated diabetes symptoms, where as control IgG-Fc had no effect. Treatment with GLP-1/IgG-Fc or Ex4/IgG-Fc improved glucose tolerance and increased circulating insulin and GLP-1 levels. It also significantly enhanced islet beta-cell mass, which is likely a major factor in the amelioration of diabetes. This suggests that GLP-1/IgG-Fc gene therapy may be applicable to diseases where there is either acute or chronic beta-cell injury.
journal_name
Gene Therjournal_title
Gene therapyauthors
Soltani N,Kumar M,Glinka Y,Prud'homme GJ,Wang Qdoi
10.1038/sj.gt.3302944subject
Has Abstractpub_date
2007-06-01 00:00:00pages
981-8issue
12eissn
0969-7128issn
1476-5462pii
3302944journal_volume
14pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Replication-deficient retroviruses have been successfully utilized as vectors, offering an efficient, stable method of therapeutic gene delivery. Many examples exist proving this mode of integrative gene transfer is both effective and safe in cultured systems and clinical trials. Along with their success, severe side ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2012.88
更新日期:2013-06-01 00:00:00
abstract::A major concern of using viral gene therapy is the potential for uncontrolled vector propagation and infection that might result in serious deleterious effects. To enhance the safety, several viral vectors, including vectors based on Sindbis virus, were engineered to lose their capability to replicate and spread after...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.153
更新日期:2009-02-01 00:00:00
abstract::Neonatal AAV8-mediated Factor IX (F.IX) gene delivery was applied as a model for exploring mechanisms of tolerance induction during immune ontogeny. Intraperitoneal delivery of AAV8/ Factor IX (hF.IX) during weeks 1-4 of life, over a 20-fold dose range, directed stable hF.IX expression, correction of coagulopathy in F...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.22
更新日期:2013-10-01 00:00:00
abstract::Urea cycle defects presenting in the neonatal period with hyperammonaemia are associated with high morbidity and mortality, and necessitate liver transplantation for long-term management. Gene therapy is therefore an attractive possibility, with vectors based on adeno-associated virus (rAAV) currently showing exciting...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.51
更新日期:2013-12-01 00:00:00
abstract::Glucagon-like peptide-1 (GLP-1) is an incretin hormone that performs a wide array of well-characterized antidiabetic actions, including stimulation of glucose-dependent insulin secretion, upregulation of insulin gene expression and improvements in beta-cell survival. GLP-1-receptor agonists have been developed for tre...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.143
更新日期:2010-02-01 00:00:00
abstract::A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication. Simultaneously, however, it may also enhance antitumor therapy through initiation of proinflammatory, antiviral cytokine responses at the tumor site. The aim of this study was to investigate ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.161
更新日期:2010-02-01 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::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::Gene transfer technology has opened novel treatment avenues toward the treatment of damaged musculoskeletal tissues, and may be particularly beneficial to articular cartilage. There is no natural repair mechanism to heal damaged or diseased cartilage. Existing pharmacologic, surgical and cell based treatments may offe...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302201
更新日期:2004-02-01 00:00:00
abstract::Citrullinemia type 1 (CTLN1) is an autosomal recessive disorder of metabolism caused by a deficiency of argininosuccinate synthetase. Despite optimal management, CTLN1 patients still suffer from lethal metabolic instability and experience life-threatening episodes of acute hyperammonemia. A murine model of CTLN1 (fold...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.53
更新日期:2013-12-01 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::Different lipids and cationic polymers were tested in vitro for their ability to transfect rabbit aortic smooth muscle cells and human endothelial cells with lacZ marker gene. Toxicity of the complexes was evaluated with MTT assay. Selected plasmid-polymer complexes with different charge ratios were then tested for in...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300800
更新日期:1999-01-01 00:00:00
abstract::In this study, self-inactivating (SIN) retroviral vectors based on feline foamy virus (FFV) were constructed and analysed. The FFV SIN vectors were devoid of the core FFV long terminal repeat promoter plus upstream sequences but contained all structural and regulatory genes. This design allowed sensitive detection of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302185
更新日期:2004-03-01 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::Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher ef...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-018-0005-z
更新日期:2018-04-01 00:00:00
abstract::Cytomegalovirus (CMV) promoter is often present in recombinant adenovirus vectors (AdVs) suitable for gene therapy, ensuring high levels of transgene production in a wide range of hosts. Despite this characteristic, the presence of the AdV genome in target cells and tissues typically lasts longer than transgene produc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301296
更新日期:2000-10-01 00:00:00
abstract::Mucopolysaccharidosis type IIIA (MPS-IIIA) or Sanfilippo A syndrome is a lysosomal storage genetic disease that results from the deficiency of the N-sulfoglucosamine sulfohydrolase (SGSH) protein, a sulfamidase required for the degradation of heparan sulfate glycosaminoglycans (GAGs). The accumulation of these macromo...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.75
更新日期:2014-12-01 00:00:00
abstract::Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.60
更新日期:2009-09-01 00:00:00
abstract::Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attra...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300746
更新日期:1998-10-01 00:00:00
abstract::Radioiodide concentrating activity in the thyroid, mediated by human Na+/I- symporter (hNIS), provides a mechanism for effective radioiodide treatment for patients who have invasive, recurrent, and metastatic thyroid cancers after total thyroidectomy. In an attempt to develop hNIS gene transfer for radioiodide therapy...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301170
更新日期:2000-05-01 00:00:00
abstract::Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302786
更新日期:2006-10-01 00:00:00
abstract::An invasive Escherichia coli expressing the inv gene from Yersinia pseudotuberculosis was used as a vector for protein delivery to mammalian epithelial cells. Upon incubation with beta1-integrin-expressing mammalian cells, the bacteria are internalized, allowing bacteria-encoded proteins to function from within the ma...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302281
更新日期:2004-08-01 00:00:00
abstract::The existence of cells with stem cell-like abilities derived from various tissues can now be extended to include the skeletal muscle compartment. Although researchers have focused on the utilization of these cells with regard to their myogenic capacity, initially exploring more efficient cellular therapy treatments fo...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3301719
更新日期:2002-05-01 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::Solid tumors meet their demands for nascent blood vessels and increased glycolysis, to combat hypoxia, by activating multiple genes involved in angiogenesis and glucose metabolism. Hypoxia inducible factor-1 (HIF-1) is a constitutively expressed basic helix-loop-helix transcription factor, formed by the assembly of HI...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301388
更新日期:2001-04-01 00:00:00
abstract::Improving the therapeutic potential of adenoviral (Ad) suicide gene therapy has become an area of intense investigation since the inception of gene therapy strategies for cancer treatment. Poor efficiency of gene transfer to target tissues has become one of the most important limitations to Ad-based gene therapy. Sinc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300987
更新日期:1999-09-01 00:00:00
abstract::Exogenous osteoprotegerin (OPG) gene modification appears a therapeutic strategy for osteolytic aseptic loosening. The feasibility and efficacy of a cell-based OPG gene delivery approach were investigated using a murine model of knee prosthesis failure. A titanium pin was implanted into mouse proximal tibia to mimic a...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.64
更新日期:2010-10-01 00:00:00
abstract::Varying degrees of metabolic abnormalities mediated by chronic inflammation are implicated in the chronic glomerular injuries associated with obesity. Interleukin (IL)-10, a pleiotropic cytokine, exerts anti-inflammatory effects in numerous biological settings. In the present study, we explored the biological benefits...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.183
更新日期:2012-05-01 00:00:00
abstract::Constitutive expression of short hairpin RNAs (shRNAs) may cause cellular toxicity in vivo and using microRNA (miRNA) scaffolds can circumvent this problem. Previously, we have shown that embedding small interfering RNA sequences targeting apolipoprotein B100 (ApoB) in shRNA (shApoB) or miRNA (miApoB) scaffolds result...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.58
更新日期:2014-01-01 00:00:00
abstract::The broad host cell range and high expression levels of transgenes are features that have made alphaviruses attractive for gene expression studies and gene therapy applications. Particularly, Semliki Forest virus vectors have been applied for large-scale production of recombinant membrane proteins for drug screening p...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302620
更新日期:2005-10-01 00:00:00