Abstract:
:Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the epidermis and observed HBD3 in the intercellular spaces and lamellar bodies of the upper epidermal layers. This result showed HBD3 expressed and assembled in the outer layers of the epidermis was suspected to counter the invading microorganisms. Next, we established a keratinocyte cell line that stably expressed HBD3 and found that the culture medium showed antibacterial activity. Furthermore, we prepared an epidermal sheet of these cells with the HBD3 gene and grafted this onto a dermal wound on a nude rat. The HBD3 engineered epidermis demonstrated significant antimicrobial activity. Skin ulcers without epidermis are constantly exposed to invading microorganisms. Biopsy samples of re-epithelizing epidermis from patients with skin ulcers were collected, and HBD3 mRNA level measured in the epidermis. The epidermal samples from the ulcer skin expressed 2.5 times higher levels of HBD3 transcript than those in the control skin. These results, taken together, indicate that the therapeutic introduction of the HBD3 gene into somatic cells may provide a new gene therapy strategy for intractable infectious diseases.
journal_name
Gene Therjournal_title
Gene therapyauthors
Sawamura D,Goto M,Shibaki A,Akiyama M,McMillan JR,Abiko Y,Shimizu Hdoi
10.1038/sj.gt.3302472subject
Has Abstractpub_date
2005-05-01 00:00:00pages
857-61issue
10eissn
0969-7128issn
1476-5462pii
3302472journal_volume
12pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells, retinal pigment epithelial cells, Müller cells and endothelial cells. Endothelial cell proliferation is a common feature of prolife...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302718
更新日期:2006-05-01 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::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::Although systemic administration of neutralizing anti-TNF antibodies has been used successfully in treating rheumatoid arthritis, there is a potential for side effects. We transduced a collagen reactive T-cell hybridoma with tissue-specific homing properties to assess therapeutic effects of local delivery to inflamed ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301980
更新日期:2003-08-01 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::Mobilized blood CD34+ cells from cancer patients were ex vivo infected by a recombinant adenovirus vector carrying an alkaline phosphatase gene, whose expression is evaluable by flow cytometry. A mean of 40% CD34+ cells were infected by the vector, with high levels of expression of the transgene. Among attempts to imp...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300620
更新日期:1998-04-01 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::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::Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vasc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300664
更新日期:1998-07-01 00:00:00
abstract::There is growing interest in gene delivery to the eye in order to develop gene therapy for the many ocular disorders which may be amenable to this approach. To date, recombinant adenoviruses (AV) have been the main vector used for gene delivery to anterior and posterior segments in animal models. As with delivery to o...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300761
更新日期:1998-11-01 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::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::In-stent restenosis results exclusively from neointimal hyperplasia due to mechanical injury and a foreign body response to the prosthesis. Inflammation mediated by monocyte chemoattractant protein-1 (MCP-1) might therefore underlie in-stent restenosis. We recently devised a new strategy for anti-MCP-1 gene therapy by...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302288
更新日期:2004-08-01 00:00:00
abstract::To achieve high transgene expression in the liver, we have compared the reporter gene expression among various murine retroviral long terminal repeats (LTRs) or leader sequences in vitro. Transient reporter gene expression assays revealed the highest gene expression by the polycythemic strain of spleen focus-forming v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301655
更新日期:2002-02-01 00:00:00
abstract::The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of in...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.2
更新日期:2015-05-01 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::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::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::Aptamers are oligonucleotides evolved in vitro or in nature to bind target ligands with high affinity and specificity. They are emerging as powerful tools in the fields of therapeutics, drug development, target validation and diagnostics. Aptamers are attractive alternatives to antibody- and small-molecule-based thera...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302900
更新日期:2007-02-01 00:00:00
abstract::A novel synthetic polypeptide designed as a DNA binding-molecule for liver-specific, receptor-mediated, gene transfer was used to selectively introduce reporter genes into liver cells in the form of plasmid DNA-ligand complexes. The polypeptide was a D-lysine/D-serine copolymer (Lys/Ser = 33/36 or 53/60) modified with...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300868
更新日期:1999-04-01 00:00:00
abstract::Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth f...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.153
更新日期:2010-03-01 00:00:00
abstract::Chemically inducible gene switches that regulate expression of endogenous genes have multiple applications for basic gene expression research and gene therapy. Single-chain zinc-finger transcription factors that utilize either estrogen receptor homodimers or retinoid X receptor-alpha/ecdysone receptor heterodimers are...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.96
更新日期:2008-09-01 00:00:00
abstract::The umbilical cord provides a rich source of primitive mesenchymal stem cells (human umbilical cord mesenchymal stem cells (HUMSCs)), which have the potential for transplantation-based treatments of Parkinson's Disease (PD). Our pervious study indicated that adenovirus-associated virus-mediated intrastriatal delivery ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.152
更新日期:2011-04-01 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::A novel class of cationic hyperbranched polymers, containing branched oligoethylenimine (OEI 800 Da) as core, diacrylate esters as linkers and oligoamines as surface modification, was synthesized and evaluated regarding their structure-activity relationship as gene carriers. We show that pseudodendritic core character...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303046
更新日期:2008-01-01 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::Autonomous parvoviruses are small, single strand DNA viruses which preferentially replicate in transformed and tumor cells, causing cell death by expression of the cytotoxic nonstructural protein, NS1. Several parvoviruses of the rodent group, including LuIII, efficiently infect human transformed cell lines. The poten...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300832
更新日期:1999-03-01 00:00:00
abstract::Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leadin...
journal_title:Gene therapy
pub_type: 信件,评审
doi:10.1038/s41434-018-0004-0
更新日期:2018-04-01 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::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