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 reaction. A deletion mutant of pCMVbeta was used as an internal standard. After intravenous administration of PEI/DNA complexes, the serum levels of DNA rapidly declined for up to 15 min. However, after this point, the serum levels of DNA diminished slowly. At 15 min after dose, PEI/DNA complexes showed 33-fold higher distribution of DNA in the lung than did naked DNA. At 24 h, all the organs tested showed much higher levels of plasmid DNA in PEI/DNA complexes, with distribution in the liver and lung being three orders of magnitude higher than naked DNA. The mRNA expression of DNA was observed in various organs of PEI/DNA-treated mice at 12 days after dose. Once a week dosing of PEI/DNA complexes over 3 consecutive weeks did not alter the histology of the organs. However, twice a week dosing over 3 weeks induced a sign of inflammation in the liver. These results indicate that PEI enhances the delivery and retention of plasmid DNA in the organs, especially the liver, but that safe delivery requires proper dosing intervals.
journal_name
Gene Therjournal_title
Gene therapyauthors
Oh YK,Kim JP,Yoon H,Kim JM,Yang JS,Kim CKdoi
10.1038/sj.gt.3301516keywords:
subject
Has Abstractpub_date
2001-10-01 00:00:00pages
1587-92issue
20eissn
0969-7128issn
1476-5462journal_volume
8pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract：:The broad host cell range and high expression levels of transgenes are features that have made alphaviruses attractive for gene expression studies and gene therapy applications. Particularly, Semliki Forest virus vectors have been applied for large-scale production of recombinant membrane proteins for drug screening p...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.gt.3302620
更新日期：2005-10-01 00:00:00
abstract：:Integration site analysis was performed on six dogs with canine leukocyte adhesion deficiency (CLAD) that survived greater than 1 year after infusion of autologous CD34+ bone marrow cells transduced with a gammaretroviral vector expressing canine CD18. A total of 387 retroviral insertion sites (RIS) were identified in...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2008.52
更新日期：2008-07-01 00:00:00
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...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302472
更新日期：2005-05-01 00:00:00
abstract：:We introduce a lung inflation-fixation protocol to examine the distribution and gene transfer efficiency of fluorescently tagged lipoplexes using fluorescence confocal microscopy within thick lung tissue sections. Using this technique, we tested the hypothesis that factors related to lipoplex distribution were the pre...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301461
更新日期：2001-06-01 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：: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：:The mouse is widely used as a model for DNA therapy and vaccination even though the efficiency of DNA delivery in higher mammals and humans is much less. The human APOBEC3 (A3) enzymes impact viral genomes by cytidine deamination, which introduces multiple uridine residues into single-stranded DNA, a process known as ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2014.88
更新日期：2015-01-01 00:00:00
abstract：:The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)bet...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301689
更新日期：2002-05-01 00:00:00
abstract：:In this study, self-inactivating (SIN) retroviral vectors based on feline foamy virus (FFV) were constructed and analysed. The FFV SIN vectors were devoid of the core FFV long terminal repeat promoter plus upstream sequences but contained all structural and regulatory genes. This design allowed sensitive detection of ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302185
更新日期：2004-03-01 00:00:00
abstract：:Rhesus macaque tripartite motif (TRIM)5alpha potently inhibits early stages of human immunodeficiency virus (HIV)-1 replication, while the human orthologue has little effect on this virus. We used PCR-based random mutagenesis to construct a large library of human TRIM5alpha variants containing mutations in the PRYSPRY...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2010.40
更新日期：2010-07-01 00:00:00
abstract：:This report examines the commercialization of gene therapy in the context of innovation theories that posit a relationship between the maturation of a technology through its life cycle and prospects for successful product development. We show that the field of gene therapy has matured steadily since the 1980s, with th...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2013.72
更新日期：2014-02-01 00:00:00
abstract：:We have designed new vectors for the construction of recombinant adenoviruses containing expression cassettes in the E1 and/or E3 regions. Using a versatile set of restriction enzymes, the cassettes are cloned into small bacterial vectors and subsequently introduced into large plasmids containing the adenoviral sequen...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301047
更新日期：2000-01-01 00:00:00
abstract：:Different lipids and cationic polymers were tested in vitro for their ability to transfect rabbit aortic smooth muscle cells and human endothelial cells with lacZ marker gene. Toxicity of the complexes was evaluated with MTT assay. Selected plasmid-polymer complexes with different charge ratios were then tested for in...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300800
更新日期：1999-01-01 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：:Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 (Ex4) have displayed potent glucose homeostasis-modulating characteristics in type 2 diabetes (T2D). However, there are few reports of effectiveness in type 1 diabetes (T1D) therapy, where there is massive loss of beta cells. We previously described a novel GL...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302944
更新日期：2007-06-01 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：:Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA hu...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301274
更新日期：2000-09-01 00:00:00
abstract：:As clinical gene therapy has progressed toward realizing its potential, concern over misuse of the technology to enhance performance in athletes is growing. Although 'gene doping' is banned by the World Anti-Doping Agency, its detection remains a major challenge. In this study, we developed a methodology for direct de...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2010.49
更新日期：2010-08-01 00:00:00
abstract：:Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non-lethal diseases. They possess distinct properties that make them particularly suitable...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/gt.2011.153
更新日期：2012-02-01 00:00:00
abstract：:We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate marke...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300565
更新日期：1998-01-01 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：:Multiple antitumor modalities may be necessary to overcome lung tumor-mediated immunosuppression and effectively treat non-small cell lung cancer (NSCLC). To evaluate a multimodality gene therapy approach for control of local tumor growth, a weakly immunogenic murine alveolar cell carcinoma, L1C2, was transduced with ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300531
更新日期：1997-12-01 00:00:00
abstract：:Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the treatment of neurodegenerative diseases. While AAVs are generally administered systemically to newborns in preclinical studies of neurological disorders, in adults the maturity of the blood-brain barrier (BBB) must be considered when selecti...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2017.18
更新日期：2017-05-01 00:00:00
abstract：:Prostate cancer is the most common cancer in men of the western world. To date, no effective treatment exists for metastatic prostate cancer and consequently, there is an urgent need to develop new and improved therapeutics. In recent years, the therapeutic potential of RNA interference (RNAi) has been extensively exp...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2015.50
更新日期：2015-10-01 00:00:00
abstract：:Transplantation faces several major obstacles that could be overcome by expression of immunomodulatory proteins through application of gene therapy techniques. Gene therapy strategies to prolong graft survival involve gene transfer of immunosuppressive or graft-protecting molecules. Very promising results have been ob...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.gt.3301083
更新日期：2000-01-01 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：: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：:Morphine appears to be the most active metabolite of heroin; therefore, the effects of morphine are important in understanding the ramifications of heroin abuse. Opioid physical dependence (withdrawal response) may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced dru...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2017.22
更新日期：2017-05-01 00:00:00
abstract：:Self-amplifying RNA (saRNA) is a promising biotherapeutic tool that has been used as a vaccine against both infectious diseases and cancer. saRNA has been shown to induce protein expression for up to 60 days and elicit immune responses with lower dosing than messenger RNA (mRNA). Because saRNA is a large (~9500 nt), n...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/s41434-019-0095-2
更新日期：2019-09-01 00:00:00
abstract：:This study examines the clinical relevance of tissue engineering integrating gene therapy and polymer science to bone regeneration. Bilateral maxillary defects (3 x 1.2 cm(2)) in 20 miniature swine were bridged with a bioresorbable internal splint. Constructs were created using ex vivo adenovirus bone morphogenetic pr...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302106
更新日期：2003-11-01 00:00:00
