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 markers using the adenovirus delivery method. Rate of weight loss and percentage satiety were significantly greater in the mice treated with Adleptin. These findings were associated with lower peak serum leptin levels with Ad-leptin (22.9 +/- 2.6 ng/ml for the human gene, and 48.9 +/- 11.5 ng/ml for the murine gene) compared to rh-leptin (385.2 +/- 36.0 ng/ml). (Values are given as mean +/- standard error of the mean.) Importantly rh-leptin and ex vivo-expressed Ad-leptin were equivalently active in a functional cell-based assay. The primary difference in the two therapeutic approaches is the continuous chronic secretion of leptin mediated by gene delivery, versus the intermittent bolus delivery and rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo findings suggest that leptin effects are better achieved at lower steady-state levels, a pharmacological feature attained here by gene therapy. These findings may have implications for the potential use of leptin in the treatment of obesity.
journal_name
Gene Therjournal_title
Gene therapyauthors
Morsy MA,Gu MC,Zhao JZ,Holder DJ,Rogers IT,Pouch WJ,Motzel SL,Klein HJ,Gupta SK,Liang X,Tota MR,Rosenblum CI,Caskey CTdoi
10.1038/sj.gt.3300565subject
Has Abstractpub_date
1998-01-01 00:00:00pages
8-18issue
1eissn
0969-7128issn
1476-5462journal_volume
5pub_type
杂志文章相关文献
GENE THERAPY文献大全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::The role of two receptors, previously proposed to mediate the entry of adenoviruses into human cells, the coxsackie and adenovirus receptor (CAR) and the major histocompatibility complex (MHC) class I heavy chain has been investigated. The expression of MHC class I in many tumours is reduced or absent, therefore if th...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301006
更新日期:1999-09-01 00:00:00
abstract::Sindbis virus expression has been used for in vitro investigations of antigen processing, presentation and epitope mapping. The recent development of a replication-deficient recombinant Sindbis virus expression vector has made in vivo expression possible with minimal pathogenic risk. Advantages of Sindbis virus over o...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300458
更新日期:1997-08-01 00:00:00
abstract::The potential of gene therapy for treatment of lung disease remains unrealised. Early model systems often resulted in promising efficiency of gene transfer, only to prove irreproducible in the clinic. While problems such as induction of host immune responses and duration of expression also need to be addressed, it is ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301146
更新日期:2000-04-01 00:00:00
abstract::We report on systemic delivery and long-term biological effects of apolipoprotein E (apoE) obtained by intramuscular (i.m.) plasmid DNA injection. ApoE plays an important role in lipoprotein catabolism and apoE knock-out mice develop severe hypercholesterolemia and diffuse atherosclerosis. We have injected apoE-defici...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301310
更新日期:2000-11-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Gene therapy
pub_type: 已发布勘误
doi:10.1038/s41434-020-00186-x
更新日期:2020-08-01 00:00:00
abstract::Current generation adenovirus (Ad) vectors are deleted for the E1 region of genes and require propagation in E1 expressing 293 cells. Expression of genes delivered by Ad vectors into immunocompetent hosts is generally transient since the current vectors are not completely replication defective. Viral proteins expresse...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300378
更新日期:1997-03-01 00:00:00
abstract::Replication defective viral vectors provide a potentially useful means of gene transfer to oligodendrocytes and thus for studying the pathogenesis of white matter disease. In this study we have examined the expression pattern of E1/E3 deleted adenoviral vectors expressing the reporter gene LacZ (AdlacZ) as a means of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300971
更新日期:1999-08-01 00:00:00
abstract::betaTC-tet cells are conditionally immortalized pancreatic beta cells which can confer long-term correction of hyperglycemia when transplanted in syngeneic streptozocin diabetic mice. The use of these cells for control of type I diabetes in humans will require their encapsulation and transplantation in non-native site...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300922
更新日期:1999-06-01 00:00:00
abstract::A retroviral vector constructed from the murine leukemia virus (MLV) can only express transgenes in cells undergoing mitosis, indicating its suitability as a delivery vehicle for cancer gene therapy. However, the transduction efficiency (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301390
更新日期:2001-02-01 00:00:00
abstract::Recombinant adenoviruses (Ad) are attractive vectors for gene transfer in vitro and in vivo. However, the widely used E1-deleted vectors as well as newer generation vectors contain viral sequences, including transcriptional elements for viral gene expression. These viral regulatory elements can interfere with heterolo...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301139
更新日期:2000-04-01 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::The ability to restrict gene delivery and expression to particular cell types is of paramount importance for many types of gene therapy, especially in the lung. The alveolar epithelial type I (ATI) cell, in particular, is an attractive cell type to target, as it comprises 95% of the internal surface area of the lung. ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.52
更新日期:2016-10-01 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::The proteasome is a multisubunit cytosolic protein complex responsible for degrading cytosolic proteins. Several studies have implicated its involvement in the processing of viral particles used for gene delivery, thereby limiting the efficiency of gene transfer. Peptide-based nonviral gene delivery systems are suffic...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302575
更新日期:2005-11-01 00:00:00
abstract::Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2017.37
更新日期:2017-07-01 00:00:00
abstract::Vectors conjugated with ligands recognized by cell surface receptors are of interest for cystic fibrosis gene therapy since these vectors would allow cell-specific targeting. However, an efficient and specific uptake may be abrogated by a subsequent intracellular trafficking leading to an inefficient gene transfer. Th...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301738
更新日期:2002-06-01 00:00:00
abstract::The mechanism whereby cationic lipids destabilize cell membranes to facilitate the intracellular delivery of macromolecules such as plasmid DNA or antisense oligonucleotides is not well understood. Here, we show that cationic lipids can destabilize lipid bilayers by promoting the formation of nonbilayer lipid structur...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301506
更新日期:2001-08-01 00:00:00
abstract::Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.158
更新日期:2011-05-01 00:00:00
abstract::We have comparatively evaluated the efficiency of a series of retroviral vectors transducing the gp91-phox gene, whose defects are responsible for impaired production of superoxide anion (O2-) by phagocytic cells and lead to the X-linked form of chronic granulomatous disease (X-CGD). These vectors included four constr...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301057
更新日期:2000-01-01 00:00:00
abstract::This work demonstrates that electrical muscle stimulation markedly increases the transfection efficiency of an intramuscular injection of plasmid DNA. In soleus or extensor digitorum longus muscles of adult rats the percentage of transfected fibers increased from about 1 to more than 10. The number of transfected fibe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300847
更新日期:1999-04-01 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
abstract::Lentiviral vectors pseudotyped with the baculovirus envelope protein GP64 transduce primary cultures of human airway epithelia (HAE) at their apical surface. Our goal in this study was to harness a directed evolution approach to develop a novel envelope glycoprotein with increased transduction properties for HAE. Usin...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2017.78
更新日期:2017-10-01 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::Lentivirus can be engineered to be a highly potent vector for gene therapy applications. However, generation of clinical grade vectors in enough quantities for therapeutic use is still troublesome and limits the preclinical and clinical experiments. As a first step to solve this unmet need we recently introduced a bac...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.162
更新日期:2011-06-01 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::Development of efficient short-term gene transfer technologies for embryonic stem (ES) cells is urgently needed for various existing and new ES cell-based research strategies. In this study, we present a highly efficient, nonviral non-DNA technology for genetic loading of mouse ES cells based on electroporation of def...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302342
更新日期:2004-11-01 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::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