Abstract:
:This study was designed to evaluate the utility of positron emission tomography (PET) to quantify the magnitude and spatial distribution of transgene expression after different methods of adenoviral vector delivery (with surfactant- and saline-based vehicles) within rat lungs. In all, 17 animals (eight in the surfactant group, nine in the saline group) were studied 3 days after intratracheal administration of a replication-incompetent adenovirus encoding a mutant Herpes simplex virus-1 thymidine kinase (mHSV1-TK)-enhanced green fluorescent protein fusion gene driven by a Cytomegalovirus promoter (Ad-CMV-mNLS-HSV1sr39tk-egfp). PET images were obtained 1 h after i.v. administration of 9-(4-[(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]-FHBG), an imaging substrate for mHSV1-TK. Overall, the average lung concentration of [(18)F]-FHBG was significantly greater in the surfactant group than in the saline group (0.24+/-0.06 versus 0.17+/-0.03% injected dose/ml lung, P< or =0.05). Lung [(18)F]-FHBG distribution was more peripheral and more homogeneous in the surfactant group than in the saline group (mean coefficient of variation=31+/-4 versus 36+/-3%, respectively, P< or =0.05). Regions of increased tracer concentration in the surfactant group compared to the saline group were evenly distributed throughout the lungs. We conclude that PET imaging provides useful and meaningful information about the effectiveness of different gene transfer delivery strategies within the lungs, and that surfactant-based vehicles may be a superior strategy for pulmonary gene transfer.
journal_name
Gene Therjournal_title
Gene therapyauthors
Richard JC,Factor P,Welch LC,Schuster DPdoi
10.1038/sj.gt.3302117keywords:
subject
Has Abstractpub_date
2003-12-01 00:00:00pages
2074-80issue
25eissn
0969-7128issn
1476-5462pii
3302117journal_volume
10pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Regulated expression of therapeutic genes is required for long-term gene therapy applications for many disorders. Here we describe a doxycycline (dox)-regulated lentiviral vector system consisting of two HIV-1-based self-inactivating viruses. One of the vectors is constitutively expressing a novel improved version of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301889
更新日期:2003-03-01 00:00:00
abstract::Recently, there has been an increasing level of interest in electroporation for gene delivery due to the site-specific nature of the delivery, as well as the high efficiency of the method. Electroporation involves the application of a pulsed electric field to cells to enhance cell permeability, resulting in the transi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301733
更新日期:2002-08-01 00:00:00
abstract::Adoptive immunotherapy of cancer using chimeric antigen receptor (CAR)-engineered T cells with redirected specificity showed efficacy in recent trials. In preclinical models, 'second-generation' CARs with CD28 costimulatory domain in addition to CD3ζ performed superior in redirecting T-cell effector functions and surv...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.127
更新日期:2011-01-01 00:00:00
abstract::We have previously established a stable HIV-1 packaging cell line, psi 422, which yielded high titers of an HIV-1 vector capable of efficiently transducing CD4+ cells. In order to increase the safety of this gene delivery system, we have now replaced the HIV-1 vector with an HIV-2 vector to abolish any risk of homolog...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300563
更新日期:1998-01-01 00:00:00
abstract::Many retroviral vectors based on murine leukaemia virus (MLV) contain the first 420 nucleotides of the gag gene, as this was reported to increase vector titre by increasing the efficiency of RNA packaging. In this study, deletion of this gag sequence from its original location did not decrease the titre of two retrovi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301081
更新日期:2000-02-01 00:00:00
abstract::VP22, a structural protein from herpes simplex virus type I, exhibits the unique property of intercellular trafficking. This protein is exported from primary expressing cells and subsequently imported into neighbouring cells. This property is conserved when VP22 is genetically fused to a protein, making it a promising...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301904
更新日期:2003-02-01 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::Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replica...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2009.27
更新日期:2009-04-01 00:00:00
abstract::Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being introduced into clin...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3303067
更新日期:2008-01-01 00:00:00
abstract::Most neoplasms do not induce antitumor immune responses that can control tumor growth. Tumor associated antigens (TAAs) are insufficiently immunogenic. A vaccine that augments the immunogenic properties of TAAs could be of importance in the treatment of cancer patients. In an animal model, we prepared a vaccine by tra...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301765
更新日期:2002-09-01 00:00:00
abstract::Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF), and at a molecular level reduced expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) is a major contributor. Previous studies in small animals have suggested that restoration of SERCA function is benef...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.120
更新日期:2008-12-01 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
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::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::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::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::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::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::Intraperitoneal (i.p.) recurrence of cisplatin-refractory and p53 mutant ovarian cancer is a major clinical problem, despite surgery and chemotherapy. dl1520 (ONYX-015) is an E1B-55 kDa gene-deleted adenovirus engineered selectively to replicate in and destroy cancer cells lacking functional p53. However, a correlatio...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301319
更新日期:2000-11-01 00:00:00
abstract::In 2012, we reported that 5 out of 11 subjects in a clinical trial (NCT00372320) administering AdhAQP1 to radiation-damaged parotid glands showed increased saliva flow rates and decreased symptoms over the initial 42 days. AdhAQP1 is a first-generation, E1-deleted, replication-defective, serotype 5 adenoviral vector e...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.55
更新日期:2015-09-01 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::Homologous restriction factor 20 (HRF20, CD59) is one of the complement regulatory factors. In this study, the complement-resistant retroviral vector, which possesses the HRF20 gene as a selection gene, was constructed and examined. The virus-producing cell, transduced with complement-resistant retroviral vector, was ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300574
更新日期:1998-02-01 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::Genetic engineering of T lymphocytes for adoptive clinical immunotherapy calls for efficient gene transduction methods. Therefore, a transient retroviral gene transduction system 'STITCH' was developed comprising pSTITCH retroviral vector encoding the transgene, plasmids encoding Moloney murine leukemia virus gag/pol ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300696
更新日期:1998-09-01 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::Viral gene vectors often rely on packaging cell lines, which provide the necessary factors in trans for the formation of virus-like particles. Previously, we reported on a first-generation packaging cell line for gene vectors, which are based on the B-lymphotropic Epstein-Barr virus (EBV), a human gamma-herpesvirus. T...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302714
更新日期:2006-05-01 00:00:00
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 ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302644
更新日期:2006-02-01 00:00:00
abstract::Partial resistance of primary mouse hepatocytes to lentiviral (LV) vector transduction poses a challenge for ex vivo gene therapy protocols in models of monogenetic liver disease. We thus sought to optimize ex vivo LV gene transfer while preserving the hepatocyte integrity for subsequent transplantation into recipient...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.117
更新日期:2012-04-01 00:00:00
abstract::Soluble receptors to vascular endothelial growth factor (VEGF) can inhibit its angiogenic effect. Since angiogenesis is involved in wound repair, we hypothesized that adenovirus-mediated gene transfer of a soluble form of VEGF receptor 2 (Flk-1) would attenuate wound healing in mice. C57Bl/6J and genetically diabetic ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302162
更新日期:2004-02-01 00:00:00
abstract::We have constructed two recombinant adeno-associated virus (AAV) vectors (pJJ-3GC and pJJ-3ASA) which contained either the human glucocerebrosidase (GC) or arylsulfatase A (ASA) cDNA under the control of an SV40 promoter. These plasmids were co-transfected to 293 cells with a helper plasmid containing trans-acting AAV...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00