Abstract:
:The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long-term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development.
journal_name
Gene Therjournal_title
Gene therapyauthors
Rahim AA,Wong AM,Ahmadi S,Hoefer K,Buckley SM,Hughes DA,Nathwani AN,Baker AH,McVey JH,Cooper JD,Waddington SNdoi
10.1038/gt.2011.157subject
Has Abstractpub_date
2012-09-01 00:00:00pages
936-46issue
9eissn
0969-7128issn
1476-5462pii
gt2011157journal_volume
19pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::We evaluated the efficacy of equine infectious anaemia virus (EIAV)-based lentiviral vectors encoding endostatin (EIAV.endostatin) or angiostatin (EIAV.angiostatin) in inhibiting angiogenesis and vascular hyperpermeability in the laser-induced model of choroidal neovascularisation (CNV). Equine infectious anaemia viru...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302769
更新日期:2006-08-01 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::For patients with metastatic prostate cancer, the 5-year survival rate of 31% points to a need for novel therapies and improvement of existing modalities. We propose that p53 gene therapy and chemotherapy, when combined, will provide superior tumor cell killing for the treatment of prostate carcinoma. To this end, we ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-019-0071-x
更新日期:2020-02-01 00:00:00
abstract::Overexpression of vascular endothelial growth factor (VEGF) and its cognate receptor KDR has been linked to a more aggressive phenotype of human prostate carcinomas. The importance of signal transduction through the VEGF receptor 2 is illustrated by use of soluble KDR, which binds to VEGF and sequesters this ligand be...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302432
更新日期:2005-03-01 00:00:00
abstract::Cationic lipid-based delivery systems such as lipoplexes or stabilized plasmid-lipid particles (SPLP) represent a safer alternative to viral systems for gene therapy applications. We studied the impact of cell cycle status on the efficiency of transfection of human ovarian carcinoma tumor cells using two cationic-lipi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300837
更新日期:1999-03-01 00:00:00
abstract::Studies reviewed show that lentiviral gene therapy directed either at inhibiting the synthesis of brain acetaldehyde generated from ethanol or at degrading brain acetaldehyde fully prevent ethanol intake by rats bred for their high alcohol preference. However, after animals have chronically consumed alcohol, the above...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41434-019-0064-9
更新日期:2019-11-01 00:00:00
abstract::The annual rate of kidney graft loss caused by chronic allograft nephropathy (CAN) has not improved over the past decade. Recent reports suggest that acute renal ischemia results in development of CAN. The goal of the present study was to assess the renoprotective potential and safety of hepatocyte growth factor (HGF)...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302478
更新日期:2005-05-01 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::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::Excessive activated T-cell proliferation was observed in vivo in one patient after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient, who had chemotherapy refractory and CD19+ diffuse large B-cell lymphoma (DLBCL), received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy (f...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-017-0001-8
更新日期:2018-06-01 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::To evaluate the use of HSV-based vectors for arthritis gene therapy we have constructed a first-generation, ICP4 deficient, replication defective herpes simplex virus (HSV) vector (S/0-) and a second-generation HSV vector derivative (T/0-) deficient for the immediate-early genes ICP4, 22 and 27, each carrying a solubl...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301014
更新日期:1999-10-01 00:00:00
abstract::The efficiency with which adenoviral vectors infect airway epithelial cells in vivo is unclear despite extensive preclinical and clinical studies. Our hypothesis is that gene transfer is limited by vector internalization which is mediated by binding of a fiber with a cellular receptor and the RGD motif of the penton b...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Current experimental gene therapy approaches for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) include the use of viral vectors expressing antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes. However, since increasing evidence favors a role for alpha-synuclein accumulation in the p...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302349
更新日期:2004-12-01 00:00:00
abstract::Catheter-based percutaneous transluminal gene delivery (PTGD) into the coronary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhesion of replication...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301079
更新日期:2000-02-01 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::By-pass surgery and percutaneous transluminal (coronary) angioplasty, PT(C)A, are standard techniques for the treatment of vascular occlusions. Their usefulness is limited by by-pass graft failure and restenosis occurring after the procedures. Twenty percent of patients treated with PTCA/PTA need a new revascularizati...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3301866
更新日期:2002-11-01 00:00:00
abstract::Isolated limb perfusion (ILP) is a limb salvage surgical modality used to deliver chemotherapy and biologic agents to locally advanced and recurrent extremity soft tissue sarcoma (STS), and may be readily tailored for delivery of gene therapy. We set out to test the feasibility of delivering AdFLAGp53 (replication inc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302911
更新日期:2007-04-01 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::We have developed a novel gene transfer drug, HIV-IT(V), for the treatment of HIV infection in humans. HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env and rev genes and a neomycin resistance marker gene (neor). We have recently reported that HIV-IT(V) administered intramuscularly to male mice localizes pr...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::This study characterized gene transfer into both normal and injured adult rat dorsal spinal cord using first (E1-/E3-) or second (E1-/E2A125/E3-, temperature-sensitive; ts) generation of replication-defective adenoviral (Ad) vectors. A novel immunosuppressive regimen aimed at blocking CD4/CD45 lymphocytic receptors wa...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300774
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::Bone morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302075
更新日期:2003-09-01 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::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::The failure of pharmacological approaches to cure infection with the human immunodeficiency virus (HIV) has renewed the interest in gene-based therapies. Among the various strategies that are currently explored, the blockade of HIV entry into susceptible T cells and macrophages promises to be the most powerful interve...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302755
更新日期:2006-07-01 00:00:00
abstract::CC-chemokine receptor (CCR)-5 is the principal coreceptor for the entry of macrophage (M)-tropic HIV-1 viruses into a cell, while CXC-chemokine receptor (CXCR)-4 is the principal coreceptor for T cell line (T)-tropic HIV-1. In this study, we utilized a novel intracellular chemokine (intrakine) strategy to co-inactivat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300667
更新日期:1998-07-01 00:00:00
abstract::Newcastle disease virus (NDV) is an oncolytic paramyxovirus with a nonsegmented single-stranded RNA genome. In this report, a recombinant oncolytic NDV was passaged in human tumor xenografts and reisolated and characterized after two rounds of bioselection. Several isolates could be recovered that differed from the pa...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.13
更新日期:2013-01-01 00:00:00
abstract::A recombinant adeno-associated virus (rAAV) vector was used to overexpress the anti-apoptotic Bcl-2-family protein, BCL-w, in rat brain. Three weeks after injecting the vector into cerebral cortex and striatum on one side, temporary focal ischemia was induced by occlusion of the ipsilateral middle cerebral artery for ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301868
更新日期:2003-01-01 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