Abstract：
:We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.
journal_name
Gene Therjournal_title
Gene therapyauthors
Fang YW,Yang SS,Chau T,Nakamura M,Yamazaki O,Seki G,Yamada H,Hsu HM,Cheng CJ,Lin SHdoi
10.1038/gt.2015.7subject
Has Abstractpub_date
2015-05-01 00:00:00pages
374-81issue
5eissn
0969-7128issn
1476-5462pii
gt20157journal_volume
22pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract：:The development of efficient systems for in vivo gene transfer to the central nervous system (CNS) may provide a useful therapeutic strategy for the alleviation of several neurological disorders. In this study, we evaluated the feasibility of nonviral gene therapy to the CNS mediated by cationic liposomes. We present ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302516
更新日期：2005-08-01 00:00:00
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：:Recently developed helper virus-free methods of herpes simplex virus (HSV) amplicon vector packaging provide stocks that are virtually devoid of the cytotoxic component normally associated with traditional helper virus-based packaging methods. These approaches involve cotransfection of amplicon plasmid DNA with either...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301340
更新日期：2001-01-01 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：:The production of high-titer recombinant adeno-associated virus (rAAV) vector is essential for treatment of genetic diseases affecting the retina and choroid, where anatomical constraints may limit injectable volumes. Problematically, cytotoxicity arising from overexpression of the transgene during vector production f...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2017.50
更新日期：2017-08-01 00:00:00
abstract：:Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells, retinal pigment epithelial cells, Müller cells and endothelial cells. Endothelial cell proliferation is a common feature of prolife...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302718
更新日期：2006-05-01 00:00:00
abstract：:Adeno-associated virus (AAV) derived vectors are considered highly eligible vehicles for human gene therapy. Not only do they possess many great potential for clinical applications due to their wide range of tissue targets but also their excellent preclinical safety profile makes them particularly suitable candidates ...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.gt.3302724
更新日期：2006-05-01 00:00:00
abstract：:In vitro culture systems of human myogenic cells contribute greatly to elucidation of the molecular mechanisms underlying terminal myogenic differentiation and symptoms of neuromuscular diseases. However, human myogenic cells have limited ability to proliferate in culture. We have established an improved immortalizati...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2011.44
更新日期：2011-09-01 00:00:00
abstract：:Integration site analysis was performed on six dogs with canine leukocyte adhesion deficiency (CLAD) that survived greater than 1 year after infusion of autologous CD34+ bone marrow cells transduced with a gammaretroviral vector expressing canine CD18. A total of 387 retroviral insertion sites (RIS) were identified in...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2008.52
更新日期：2008-07-01 00:00:00
abstract：:The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of in...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2015.2
更新日期：2015-05-01 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：: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：: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：:Direct gene transfer for the treatment of human diseases requires a vector which can be administered efficiently, safely and repeatedly. Cationic liposomes represent one of the few examples that can meet these requirements. Currently, more than a dozen cationic liposome formulations have been reported. These liposomes...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：
更新日期：1995-12-01 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：: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：: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：:Efficient transduction of the peripheral nervous system (PNS) is required for gene therapy of acquired and inherited neuropathies, neuromuscular diseases and for pain treatment. We have characterized the tropism and transduction efficiency of different adeno-associated vectors (AAV) pseudotypes after sciatic nerve inj...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2011.7
更新日期：2011-06-01 00:00:00
abstract：:Deficiency in acid alpha-D-glucosidase results in Pompe's disease. Modified single-stranded oligonucleotide (ODN) was designed to correct the acid alpha-D-glucosidase gene with a C1935 --> A (Asp --> Glu) point mutation which causes a complete loss of enzymatic activity for glycogen digestion in the lysosome. The ODN ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302096
更新日期：2003-10-01 00:00:00
abstract：:Adeno-associated virus (AAV)-mediated gene delivery systems have been shown to be effective tools for gene manipulation in the inner ear. For example, hair cells (HCs) and multiple other cell types can be transduced by the local injection of AAVs into the inner ear. However, application of the AAV-mediated CRISPR/Cas9...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/s41434-020-0124-1
更新日期：2020-08-01 00:00:00
abstract：:A persistent obstacle in the use of vector systems for gene therapy has been the inability to attain high-level expression of the target gene in primary cells in vivo. The MFG retroviral vector was designed to yield improved expression over the widely used N2 or LN vectors; however, the molecular basis for this effect...
journal_title：Gene therapy
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Rhesus macaque tripartite motif (TRIM)5alpha potently inhibits early stages of human immunodeficiency virus (HIV)-1 replication, while the human orthologue has little effect on this virus. We used PCR-based random mutagenesis to construct a large library of human TRIM5alpha variants containing mutations in the PRYSPRY...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2010.40
更新日期：2010-07-01 00:00:00
abstract：:We tested the influence of overexpression of arylsulfatase A (ASA) on the activity of other sulfatases in fibroblasts from patients with metachromatic leukodystrophy (MLD). We demonstrated that the overexpression of ASA reduces the activity of various sulfatases by a small amount but does not induce an accumulation of...
journal_title：Gene therapy
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:More than one hundred different mutations in the gene encoding rhodopsin are associated with a group of retinal degenerations including retinitis pigmentosa, congenital stationary night blindness and retinitis punctata albescens. Given this large heterogeneity of mutations, it would be ideal to develop mutation-indepe...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302512
更新日期：2005-08-01 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：:We have developed a novel immunostimulatory molecule against tumor cells, composed of an anti-FcgammaRIII (CD16) scFv fused to the platelet-derived growth factor receptor (PDGFR) transmembrane region. This fusion molecule was stably expressed on the tumor cell surface and retained the ability of the parental antibody ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301575
更新日期：2001-11-01 00:00:00
abstract：:Numerous approaches in gene therapy of human cancers are focused on the establishment of cell type specific or inducible expression vectors allowing the targeted and regulated expression of therapeutic genes. Various conditionally active vectors have been created carrying promoters responding to certain factors or the...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300451
更新日期：1997-06-01 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：:During the past decade, both in vitro and in vivo studies have provided new insights into the cellular and molecular mechanisms that govern angiogenesis and arteriogenesis. However, therapeutic angiogenesis clinical trials using recombinant protein or gene therapy formulations of single angiogenic growth factors have ...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.gt.3302953
更新日期：2007-05-01 00:00:00
abstract：:A stable single vial lipoplex formulation has been developed that can be stored frozen without losing either biological activity or physical stability. This formulation was identified by systematically controlling several formulation variables and without introducing either stabilizers or surfactants. Analytical assay...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300707
更新日期：1998-09-01 00:00:00
