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 was tested for improving transgene persistence. In addition, the effect of gene transfer on nociception was also evaluated. Seven days after treatment, numerous LacZ-positive cells were observed after transfection with either viral vector. By 21 days after transfection, beta-galactosidase staining was reduced and suggestive of ongoing cytopathology in both Ad-treated groups, despite the fact that the immunogenicity of LacZ/Adts appeared less when compared with that elicited by the LacZ/Ad vector. In contrast, immunosuppressed animals showed a significant (P < or = 0.05) increase in the number of LacZ-positive cells not displaying cytopathology. In these animals, a concomitant reduction in numbers of macrophages/microglia and CD4 and CD8 lymphocytes was observed. Only animals that received LacZ/Adts and immunosuppression showed transgene expression after 60 days. Similar results were observed in animals in which the L4-L5 dorsal roots were lesioned before transfection. Gene transfer into the dorsal spinal cord did not affect nociception, independent of the adenovirus vector. These results indicate that immune blockade of the CD4/CD45 lymphocytic receptors enhanced transgene stability in adult animals with normal or injured spinal cords and that persistent transgene expression in the spinal cord does not interfere with normal neural function.
journal_name
Gene Therjournal_title
Gene therapyauthors
Romero MI,Smith GMdoi
10.1038/sj.gt.3300774keywords:
subject
Has Abstractpub_date
1998-12-01 00:00:00pages
1612-21issue
12eissn
0969-7128issn
1476-5462journal_volume
5pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Breast cancer is the leading cancer diagnosed in women and the second leading cause of cancer-related deaths in women. Current limitations to standard chemotherapy in the clinic are extensively researched, including problems arising from repeated treatments with the same drugs. The phenomenon that cancer cells become ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2016.67
更新日期:2016-12-01 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::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*)...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.7
更新日期:2015-05-01 00:00:00
abstract::HaCaT cells, a spontaneously immortalised, nontumorigenic keratinocyte line, were used as a more amenable model than primary keratinocytes for ex vivo-mediated gene transfer. These cells were transduced with retroviral vectors containing the factor IX cDNA under the control of a cytomegaloviral (CMV) promoter/enhancer...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300591
更新日期:1998-03-01 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::Prenatal gene therapy has been considered for Herlitz junctional epidermolysis bullosa (H-JEB), a lethal genodermatosis caused by the absence of any of the three subunits of laminin-5, resulting from birth in widespread blistering and erosions of skin and mucosae. To investigate this strategy in an animal model, adeno...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302832
更新日期:2006-12-01 00:00:00
abstract::We demonstrated previously that the additive-type recombinant Sendai virus (rSeV) is highly efficient for use in pulmonary gene transfer; however, rSeV exhibits inflammatory responses. To overcome this problem, we tested newly developed non-transmissible constructs, namely, temperature-sensitive F-deleted vector, rSeV...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302955
更新日期:2007-07-01 00:00:00
abstract::In the last two decades, remarkable advances have been made in the development of technologies used to engineer new aptamers and ribozymes. This has encouraged interest among researchers who seek to create new types of gene-control systems that can be made to respond specifically to small-molecule signals. Validation ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2009.81
更新日期:2009-10-01 00:00:00
abstract::Chimeric antigen receptors (CARs, immunoreceptors) are frequently used to redirect T cells with pre-defined specificity, in particular towards tumour cells for use in adoptive immunotherapy of malignant diseases. Specific targeting is mediated by an extracellularly located antibody-derived binding domain, which is joi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.91
更新日期:2010-10-01 00:00:00
abstract::The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this re...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse cancers, which contributes to the proliferation and survival of cancer cells by upregulating apoptosis inhibitors and cell cycle regulators. Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator of...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.4
更新日期:2013-01-01 00:00:00
abstract::As soon as RNA interference (RNAi) was found to work in mammalian cells, research quickly focused on harnessing this powerful endogenous and specific mechanism of gene silencing for human therapy. RNAi uses small RNAs, less than 30 nucleotides in length, to suppress expression of genes with complementary sequences. Tw...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302703
更新日期:2006-03-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscular disorder caused by a defect in the DMD gene. AAV vector-mediated micro-dystrophin cDNA transfer is an attractive approach to treatment of DMD. To establish effective gene transfer into skeletal muscle, we examined the transduction efficiency of an AAV v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301829
更新日期:2002-12-01 00:00:00
abstract::Radioiodide concentrating activity in the thyroid, mediated by human Na+/I- symporter (hNIS), provides a mechanism for effective radioiodide treatment for patients who have invasive, recurrent, and metastatic thyroid cancers after total thyroidectomy. In an attempt to develop hNIS gene transfer for radioiodide therapy...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301170
更新日期:2000-05-01 00:00:00
abstract::Cellular immunity against cancer can be achieved with viral vector- and DNA-based immunizations. In preclinical studies, cancer vaccines are very potent, but in clinical trials these potencies are not achieved yet. Thus, a rational approach to improve cancer vaccines is warranted. We previously demonstrated that the r...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.24
更新日期:2015-07-01 00:00:00
abstract::Cultured keratinocyte allografts from unrelated donors can be readily grown as sheets in large-scale cell culture and have been used as an immediate skin cover for severely burned patients. Despite the absence of passenger leukocytes and the unlimited amount of material that can be obtained for permanent skin coverage...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301656
更新日期:2002-03-01 00:00:00
abstract::Green fluorescent protein (GFP) is a widely used intracellular reporter molecule to assess gene transfer and expression. A potential use for GFP is as a co-expressed marker, to select and enrich gene-modified cells by flow cytometry. Processed peptides derived from GFP and presented by the major histocompatibility com...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300951
更新日期:1999-07-01 00:00:00
abstract::Chronic infection with hepatitis B virus (HBV) puts individuals at high risk for complicating cirrhosis and liver cancer, but available treatment to counter the virus rarely eliminates infection. Although harnessing RNA interference (RNAi) to silence HBV genes has shown the potential, achieving efficient and durable s...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.94
更新日期:2015-02-01 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::Phase 1 clinical trials of liposome-mediated gene therapy for cystic fibrosis have been completed and in all cases the expression level achieved has been low and transient. Clearly, improvements in the efficiency of gene transfer are required. It is now being recognised that delivery of high doses of DNA/liposomes to ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301097
更新日期:2000-03-01 00:00:00
abstract::Chimeric oligonucleotides have been used successfully to correct point and frameshift mutations in several cell types, as well as in animal and plant models. However, their application to primitive human blood cells has been limited. In this investigation, chimeric oligonucleotides designed to direct a site-specific n...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301610
更新日期:2002-01-01 00:00:00
abstract::Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.87
更新日期:2012-01-01 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::Sinusoidal fenestrae may restrict the transport of gene transfer vectors according to their size. Using Vitrobot technology and cryo-electron microscopy, we show that the diameter of human adenoviral serotype 5 vectors is 93 nm with protruding fibers of 30 nm. Thus, a diameter of fenestrae of 150 nm or more is likely ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302899
更新日期:2007-04-01 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::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::Cancer therapies that target a single protein or pathway may be limited by their specificity, thus missing key players that control cellular proliferation and contributing to the failure of the treatment. We propose that approaches to cancer therapy that hit multiple targets would limit the chances of escape. To this ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-019-0096-1
更新日期:2020-02-01 00:00:00
abstract::A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302275
更新日期:2004-07-01 00:00:00
abstract::Several of the current techniques for transfer of both oligonucleotide and plasmid DNA into the myocardium are impaired by low efficiency and toxicity. To improve gene transfer techniques, especially into the whole heart, a gene transfer method involving liposome in conjunction with a viral envelope (HVJ-liposome) was...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300750
更新日期:1998-11-01 00:00:00
abstract::Previous studies have demonstrated that antigen-specific tolerance could be induced by lipopolysaccharide (LPS)-stimulated B cells retrovirally transduced with an immunoglobulin-antigen (or epitope-containing peptide) fusion construct. To investigate the mechanism of this gene therapy system, we now adapted this appro...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302327
更新日期:2004-10-01 00:00:00