Abstract:
:A number of genetic disorders are manifested in cutaneous epithelium and gene therapy approaches for treatment of such diseases are being considered. A successful gene therapy protocol requires durable and correctly targeted gene expression within the tissue. The continuous renewal and high levels of compartmentalization in epidermis are two challenges for a successful gene therapy of skin disorders. For those disorders which affect the upper layers of epidermis, vectors must be available that target stem cells, but remain silent until the progeny of these cells undergo differentiation. To explore the potential of long-term and targeted vector expression in epidermis, a hybrid retroviral vector encoding the reporter enhanced green fluorescent protein (EGFP) was constructed. The viral enhancer in the long terminal repeat of the vector was replaced with a 510-bp enhancer element of the human involucrin promoter. Keratinocyte-specific expression directed by the hybrid vector was demonstrated in culture and suprabasal-specific expression was observed in organotypic human epidermal cultures. In vivo transduction of mouse skin with this hybrid vector indicated long-term and stratum-specific expression of the transgene in mouse epidermis. The design of similar vectors for various gene therapy applications constitutes an important step toward clinically effective gene therapy.
journal_name
Gene Therjournal_title
Gene therapyauthors
Ghazizadeh S,Doumeng C,Taichman LBdoi
10.1038/sj.gt.3301800keywords:
subject
Has Abstractpub_date
2002-10-01 00:00:00pages
1278-85issue
19eissn
0969-7128issn
1476-5462journal_volume
9pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Gene therapy is thought to be a promising method for the treatment of various diseases. One gene therapy strategy involves the manipulations on a process of formation of new vessels, commonly defined as angiogenesis. Angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of cardiovas...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302621
更新日期:2005-10-01 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::Dendritic cells (DC) are among the most potent antigen-presenting cells known and play an important role in the initiation of antigen-specific T-lymphocyte responses. Several recent studies have demonstrated that DC expressing vector-encoded tumor-associated antigens can induce protective and therapeutic immunity in m...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300899
更新日期:1999-05-01 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::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::The growth and metastasis of solid tumors relies on the activities of polypeptide growth factors to recruit stromal tissue and expand the tumor mass. Pleiotrophin (PTN) is a secreted growth factor with angiogenic activity that has been found to contribute to the growth and metastasis of tumors including melanoma. Here...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302398
更新日期:2005-02-01 00:00:00
abstract::Mucopolysaccharidosis type I (MPSI) is an autosomic recessive, lysosomal storage disorder due to the deficit of the enzyme α-L-iduronidase (IDUA). The disease accounts for a general impairment of tissue and organ functions, mainly including heart disease, corneal clouding, organomegaly, skeletal malformations and join...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.94
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::Oncolytic viruses hold much promise as novel therapeutic agents that can be combined with conventional therapeutic modalities. Measles virus (MV) is known to enter cells using the signaling lymphocyte activation molecule (SLAM), which is expressed on cells of the immune system. Although human breast cancer cell lines ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.44
更新日期:2013-03-01 00:00:00
abstract::To elucidate further the potential of a Semliki Forest virus (SFV) vector in vivo for gene therapy, we constructed a vector, SFV-IL12, to transfer murine IL-12 genes into tumors. A single intratumoral injection of established B16 murine melanoma with SFV-IL12 resulted in a significant inhibition of tumor growth, while...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300841
更新日期:1999-04-01 00:00:00
abstract::Defects of the mitochondrial genome cause a wide variety of clinical disorders. Except for rare cases where surgery or transplant is indicated, there is no effective treatment for patients. Genetic-based therapies are consequently being considered. On account of the difficulties associated with mitochondrial (mt) tran...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2008.91
更新日期:2008-07-01 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::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::We explored the possibility of using a genetic approach to inhibit integrin-mediated endothelial cell adhesion and survival. We constructed recombinant adenoviruses (Ads) expressing chimeric proteins consisting of the cytoplasmic and transmembrane domains of integrin beta1 (CH1), beta3 (CH3) or the beta1 transmembrane...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301236
更新日期:2000-08-01 00:00:00
abstract::Vectors conjugated with ligands recognized by cell surface receptors are of interest for cystic fibrosis gene therapy since these vectors would allow cell-specific targeting. However, an efficient and specific uptake may be abrogated by a subsequent intracellular trafficking leading to an inefficient gene transfer. Th...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301738
更新日期:2002-06-01 00:00:00
abstract::Advanced prostate cancer (PC) still remains incurable. Novel immunogene therapy shows promise as treatment strategy that can target both localized and metastasized PC. In this study, we have developed a PC-specific oncolytic adenovirus (Ad-PL-PPT-E1A) armed with fusion gene of prostate-specific antigen and CD40 ligand...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.46
更新日期:2014-08-01 00:00:00
abstract::Based on observations that DBA/2 mice develop a highly specific response towards an HLA-Cw3-derived epitope, consisting entirely of CD8+CD62L-Vbeta10+ cells, we have established an in vivo mouse model for screening a variety of immunization approaches. Responder cells were readily detectable in small samples of the pe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301942
更新日期:2003-05-01 00:00:00
abstract::Earlier this laboratory constructed a herpes simplex virus 1 recombinant (R5111) that carries a IL13 ligand inserted into glycoprotein D and can enter cells via the IL13Ralpha2 receptor commonly expressed on the surface of malignant glioma cells. In this report, we describe the properties of two recombinant viruses ca...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302685
更新日期:2006-04-01 00:00:00
abstract::Vessel wall inflammation and matrix destruction are critical to abdominal aortic aneurysm (AAA) formation and rupture. We have previously shown that urokinase plasminogen activator (uPA) is highly expressed in experimental AAA and is essential for AAA formation and expansion. In this study, we examined the effects of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303069
更新日期:2008-02-01 00:00:00
abstract::The majority of immunotherapy-based gene therapy protocols consist of ex vivo gene transfer in tumor cells. To prevent further in vivo growth, modified cells must be irradiated before reinjection into patients. The present study examines the effects of gamma-irradiation on transgene expression in transduced leukemic c...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301870
更新日期:2003-02-01 00:00:00
abstract::In an earlier study exploring the potential of gene transfer to repair myocardial conduction defects, we observed that myotubes, generated by forced expression of MyoD, exhibit reduced excitability when also modified to express connexin43 (Cx43). We hypothesized that this effect was caused by gap junction-mediated cou...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302813
更新日期:2006-11-01 00:00:00
abstract::A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication. Simultaneously, however, it may also enhance antitumor therapy through initiation of proinflammatory, antiviral cytokine responses at the tumor site. The aim of this study was to investigate ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.161
更新日期:2010-02-01 00:00:00
abstract::Naturally occurring drug resistance genes of human origin can be exploited for selection of genetically engineered cells co-expressing a desired therapeutic transgene. Their non-immunogenicity in clinical applications would be a major asset. Human cytidine deaminase (hCD) is a chemoresistance gene that inactivates cyt...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301675
更新日期:2002-04-01 00:00:00
abstract::For certain gene therapy applications, the simultaneous delivery of multiple genes would allow for novel therapies. In the case of adeno-associated virus (AAV) vectors, the limited packaging capacity greatly restricts current methods of carrying multiple transgene cassettes. To address this issue, a recombinant AAV (r...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.106
更新日期:2009-11-01 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::We have previously shown that recombinant Sendai virus (SeV) vector, derived from murine parainfluenza virus, is one of the most efficient vectors for airway gene transfer. We have also shown that SeV-mediated transfection on second administration, although reduced by 60% when compared with levels achieved after a sin...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.131
更新日期:2011-02-01 00:00:00
abstract::Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. We have devised a novel way of using magnetic nanoparticles (MNPs) to enh...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.57
更新日期:2008-06-01 00:00:00
abstract::Human adenovirus (Ad) vectors are extensively used as gene transfer vehicles. However, a serious obstacle for the use of these vectors in clinical applications is due to pre-existing immunity to human Ads affecting the efficacy of gene transfer. One of the approaches to circumvent host immune response could be the dev...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302146
更新日期:2004-01-01 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::Human immunodeficiency virus (HIV) infection ultimately leads to the destruction of the CD4+ lymphocyte subset and the onset of AIDS. In recent years, several gene therapy procedures making use of retroviral vectors that selectively target HIV susceptible cells have been proposed in order to interfere with HIV product...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300646
更新日期:1998-05-01 00:00:00