解剖学和形态学
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心理学,临床
abstract::Complexes of DNA and cationic lipid offer potential advantages for gene transfer to airway epithelia. However, we found that application of DNA-lipid (DMRIE-DOPE) complexes to primary cultures of human ciliated airway epithelia or explants of rabbit trachea generated only low levels of gene transfer. In contrast, when...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300524
更新日期:1997-11-01 00:00:00
abstract::Various methods for determining the expression of the beta-galactosidase (beta-gal) gene after retroviral transduction were compared as a means to assess retroviral titre. To allow better comparison, different retroviral vectors were constructed carrying two mutants of the green fluorescent protein and assessed as sen...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300519
更新日期:1997-11-01 00:00:00
abstract::In order to exploit differences in gene expression between normal and malignant cells for genetic prodrug-activation therapy, we have generated recombinant retroviruses containing the herpes simplex virus thymidine kinase coding region cloned downstream of sequences derived from the 5'-flanking regions of the MUC1 and...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300510
更新日期:1997-10-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) is a neurotrophic human pathogen that naturally persists in neurons in a latent state and carries a large number of viral functions which can be replaced by foreign genes to create a vector for gene therapy applications. In this report we describe a two-step method for insertion/del...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300497
更新日期:1997-10-01 00:00:00
abstract::Several groups are assessing the use of cationic lipids for respiratory gene therapy. To date no human data are available regarding the safety of intra-pulmonary cationic lipid delivery. In preparation for a trial of pulmonary delivery of the CFTR gene, we have assessed the safety of nebulised lipid GL-67/DOPE/DMPE-PE...
journal_title:Gene therapy
pub_type: 临床试验,杂志文章
doi:10.1038/sj.gt.3300481
更新日期:1997-09-01 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::Gene modification of malignant cells to express immune stimulators (cytokines and immune costimulators) has provided the basis for a novel form of immunotherapy. Using a MPSV-based retroviral vector with hygromycin resistance gene as a selectable marker, we have studied retrovirus-mediated gene transfer of an immune c...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300437
更新日期:1997-07-01 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::Polynucleotide immunization has been employed as a means of inducing immune responses through the introduction of antigen-encoding DNA. While immunization against specific tumor antigens may be achieved through this strategy, various candidate tumor antigens may not be approached via DNA-based vaccines as they represe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300423
更新日期:1997-06-01 00:00:00
abstract::To facilitate the understanding of the complex process of target gene expression and its control, we report a modified inducible system for activation or repression of target gene expression in response to an exogenously administered compound. The main component of this inducible system is a chimeric transcriptional a...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300402
更新日期:1997-05-01 00:00:00
abstract::Retroviral vectors are effective shuttle systems by introducing therapeutically relevant genes stably into the genome of proliferating cells. The majority of vectors applied for research or clinical applications use neomycin for cell selection and identification. To circumvent the time consuming and potentially toxic ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300384
更新日期:1997-04-01 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::The gene encoding E. coli nitroreductase (NTR) was expressed in the luminal cells of the mammary gland of transgenic mice using the ovine beta-lactoglobulin promoter. Treatment of NTR expressing animals with the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) resulted in a rapid and selective killing of this pop...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300367
更新日期:1997-02-01 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::Antibodies have long been used in biomedical science as in vitro tools for the identification, purification and functional manipulation of target antigens; they have been exploited in vivo for diagnostic and therapeutic applications as well. Recent advances in antibody engineering have now allowed the genes encoding a...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3300346
更新日期:1997-01-01 00:00:00
abstract::We have developed and tested a transfection compound based on synthetic peptides. It consists of a 12 amino acid DNA binding peptide (P2) with an alkyl group added to the aminoterminus (P2lip) and a peptide derived from the hemagglutinin protein (HA). The components aggregate spontaneously to particles that proved to ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::In vivo approaches to liver gene therapy will require restriction of transgene expression to hepatocytes. Since targeting of viral vectors exclusively to the liver is not easy to achieve, use of liver-specific promoters for driving expression of therapeutic genes is an interesting alternative. We have shown previously...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::Low levels of expression in haemopoietic cells of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (A Tase), is associated with the dose-limiting sensitivity of these cells to the chemotherapeutic chloroethylating and related methylating agents. Thus, the use of agents which deplete ATase such as O6-benzylg...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-10-01 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::We report the discovery, on routine screening, of a replication-competent retrovirus (RCR) produced from a third generation amphotropic packaging cell line, GP + envAM12. In this line, the gag-pol and env helper genes are located on separate plasmids to minimise the chances of recombination events that may lead to RCR...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::We tested the longevity of gene expression provided by autonomously replicating vectors. The vectors contain segments of human genomic DNA that provide efficient replication initiation and sequences derived from Epstein-Barr virus that provide nuclear retention. In order to monitor gene expression, the vectors also ca...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::Cationic liposomes provide a means to introduce genes into cells both ex vivo and in vivo. In the past few years their use has been described in several tissues, e.g. lungs, liver, endothelium, brain. In this study we evaluated a commercially available poly-cationic liposome formulation in delivering a reporter gene i...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Oligonucleotides (ODNs) show great promise in their ability to specifically inhibit single gene expression but must cross the cell membrane, escape the endosomal vesicle, and possibly traverse the nuclear membrane to arrive at their intracellular target molecules. In an attempt to improve the delivery of phosphodieste...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::The expression of naked plasmid DNA coding for firefly luciferase (pRSVluc) or a secreted protein, human-alpha-1-antitrypsin (pRcCMVhAAT) in mouse skeletal muscle was characterized following administration by an improved intramuscular injection technique. Injection guided by intense illumination along the longitudinal...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-03-01 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::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::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::We have tested the cationic liposome N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethyl-ammoniummethylsul phate, (DOTAP), for gene delivery in vitro and in vivo with a view to clinical use in gene therapy for cystic fibrosis. Delivery of lacZ cDNA-DOTAP complexes via aerosol showed promoter-dependent differences in the pat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Retroviral vectors are being used increasingly in clinical gene therapy protocols but low transduction frequencies are presenting a significant obstacle to progress. In this paper we report a simple method to enhance the efficiency of ex vivo retroviral gene transfer. Calcium chloride is added to the vector stock and ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-09-01 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::In utero somatic gene transfer may be a useful therapeutic strategy for a variety of inherited disorders. In the present study, we demonstrate transgene expression in the airways of fetal lamb lungs, 2-3 weeks after injection of Moloney murine leukemia retrovirus based vectors containing cDNA for beta-galactosidase (l...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::The E1 deleted adenoviral vectors are efficient at gene transfer to cells in culture or in animals. However, their use is limited because of an immune-mediated loss of transduced cells. This immune response is believed to result from low-level production of viral antigens from these vectors after gene transfer. The ea...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Somatic transgenesis can be used to confer endogenous production of proteins with therapeutic properties. One such product, recombinant soluble human CD4 (sCD4), has been shown to be an efficient inhibitor of human immunodeficiency virus 1 (HIV-1) in vitro, but its too short half-life in vivo has impaired long-term cl...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
abstract::Ideal methods for human gene therapy will eventually include direct gene transfer to defective tissues in a patient in vivo. Toward that goal, we have used high titer, pseudotyped retroviral vectors expressing genes for the Escherichia coli beta-galactosidase (lacZ) or hepatitis B virus surface antigen (HBsAg) to infe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Gyrate atrophy (GA) of the choroid and retina is an autosomal recessive chorioretinal degeneration, caused by deficiency of the mitochondrial matrix enzyme ornithine-delta-aminotransferase (OAT). This deficiency results in the accumulation of ornithine in the body fluids and leads to hyperornithinemia. Although the cl...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Human adenovirus (AV) is a favored vector for delivery of therapeutic genes into certain target cells, such as skeletal muscle cells for gene therapy. Here we show that replication-defective (E1 + E3 deleted) human type 5 adenovirus (AV) recombinants containing a reporter gene insert (RSV-luciferase or RSV-Lux) can ve...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-09-01 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
abstract::We have used a particular folate receptor, which is overexpressed in tumor cells, for targeted DNA delivery into these cell types. This folate receptor internalizes folate through caveolae by a process named potocytosis, which is distinct from endocytosis, through clathrin-coated pits. When folate conjugated to poly-L...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::The number of clinical trials using gene transfer technology, either active or under discussion, is increasing rapidly. However, little information is available describing the regulatory procedures or safety specifications that must be considered before initiation of such trials in Europe. We describe the procedure us...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:
更新日期:1994-03-01 00:00:00
abstract::In order to characterize protein targeting signals in polarized postmitotic cortical neurones in vitro, we have developed recombinant and amplicon type vectors derived from herpes simplex virus 1 (HSV1) to transfer genes into these cells. We examined the targeting of both bacterial proteins, which lack specific target...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00