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 joints of anti-TNF single-chain antibodies (scFv) by adoptive cellular gene therapy. Cell culture medium conditioned with 1 x 10(6) scFv producer cells/ml had TNF neutralizing capacity in vitro equivalent to 50 ng/ml anti-TNF monoclonal antibody. Adding a kappa chain constant domain to the basic scFv (construct TN3-Ckappa) gave increased in vitro stability and in vivo therapeutic effect. TN3-Ckappa blocked development of collagen-induced arthritis in DBA/1LacJ mice for >60 days. Transgene expression was detected in the paws but not the spleen of treated animals for up to 55 days postinjection. No significant variations in cell proliferation or cytokine secretion were found in splenocytes or peripheral lymphocytes. IL-6 expression was blocked in the diseased paws of mice in the scFv treatment groups compared to controls. In conclusion, we have shown that local expression of an anti-inflammatory agent blocks disease development without causing demonstrable systemic immune function changes. This is encouraging for the potential development of safe adoptive cellular therapies to treat autoimmunity.
journal_name
Gene Therjournal_title
Gene therapyauthors
Smith R,Tarner IH,Hollenhorst M,Lin C,Levicnik AU,Fathman CG,Nolan GPdoi
10.1038/sj.gt.3301980keywords:
subject
Has Abstractpub_date
2003-08-01 00:00:00pages
1248-57issue
15eissn
0969-7128issn
1476-5462pii
3301980journal_volume
10pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Parkinson's disease is a prevalent progressive degenerative disorder of the elderly. There is a current need for novel therapeutic strategies because the standard levodopa pharmacotherapy is only temporarily efficacious. Recently, there have been some high-profile successful preclinical results obtained in animal mode...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302669
更新日期:2006-03-01 00:00:00
abstract::The possibility of achieving multiple systemic expression of human interferon-beta in mice upon repeated intravenous administration of cationic liposome-DNA complex (lipoplex) was investigated. Lipoplexes containing the pentammonio lipid pcTG90 were first optimized by selecting the most efficient ratio of pcTG90 to ph...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301289
更新日期:2000-09-01 00:00:00
abstract::We constructed a melanoma-specific oncolytic adenoviral vector Ad.MCDIRESE1.71Hsp3, in which the cytosine deaminase and adenoviral E1A genes linked by the IRES sequence were under the control of a mouse tyrosinase enhancer/promoter transcriptional element in the E1 region of the vector. We also inserted the human heat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302776
更新日期:2006-08-01 00:00:00
abstract::Newcastle disease virus (NDV) is an oncolytic paramyxovirus with a nonsegmented single-stranded RNA genome. In this report, a recombinant oncolytic NDV was passaged in human tumor xenografts and reisolated and characterized after two rounds of bioselection. Several isolates could be recovered that differed from the pa...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.13
更新日期:2013-01-01 00:00:00
abstract::Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attra...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300746
更新日期:1998-10-01 00:00:00
abstract::Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being introduced into clin...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3303067
更新日期:2008-01-01 00:00:00
abstract::We have assessed whether magnetic forces (magnetofection) can enhance non-viral gene transfer to the airways. TransMAG(PEI), a superparamagnetic particle was coupled to Lipofectamine 2000 or cationic lipid 67 (GL67)/plasmid DNA (pDNA) liposome complexes. In vitro transfection with these formulations resulted in approx...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302803
更新日期:2006-11-01 00:00:00
abstract::Adeno-associated virus (AAV)-mediated gene delivery systems have been shown to be effective tools for gene manipulation in the inner ear. For example, hair cells (HCs) and multiple other cell types can be transduced by the local injection of AAVs into the inner ear. However, application of the AAV-mediated CRISPR/Cas9...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-020-0124-1
更新日期:2020-08-01 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 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::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::Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS), where suspected autoimmune attack causes nerve demyelination and progressive neurodegeneration and should benefit from both anti-inflammatory and neuroprotective strategies. Although neuroprotection strategies are relatively une...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302025
更新日期:2003-05-01 00:00:00
abstract::Gene therapy with viral vectors has progressed to clinical trials. However, the localization of viral vector delivery to diseased target sites remains a challenge. We tested the hypothesis that an adenoviral vector could be successfully delivered by complexation with a specific antibody that is bound to a biodegradabl...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301452
更新日期:2001-05-01 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::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::The pseudorabies virus (PRV) is a swine alpha herpes virus that is widely used as a neural tracer because of its marked neurotropism and transneuronal transmissibility (Card et al., 1991, 1992; Strack and Loewy 1990). PRV has been used to retrogradely identify spinal cord and brainstem connections to various periphera...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 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::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::Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301636
更新日期:2002-02-01 00:00:00
abstract::Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zeal...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301395
更新日期:2001-03-01 00:00:00
abstract::Gene delivery of angiogenic growth factors is a promising approach for the treatment of ischemic cardiovascular diseases. However, success of this new therapeutic principle is hindered by the lack of critical understanding as to how disease pathology affects the efficiency of gene delivery and/or the downstream signal...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302781
更新日期:2006-09-01 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::Virus-directed enzyme prodrug therapy utilizing the bacterial enzyme nitroreductase delivered by a replication-defective adenovirus vector to activate the prodrug CB1954 is a promising strategy currently undergoing clinical trials in patients with a range of cancers. Similarly, selectively replicating oncolytic adenov...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302510
更新日期:2005-08-01 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::X-linked chronic granulomatous disease (X-CGD) is an inherited immunodeficiency with absent phagocyte NADPH-oxidase activity caused by defects in the gene-encoding gp91(phox). Here, we evaluated strategies for less intensive conditioning for gene therapy of genetic blood disorders without selective advantage for gene ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.96
更新日期:2009-12-01 00:00:00
abstract::A major concern of using viral gene therapy is the potential for uncontrolled vector propagation and infection that might result in serious deleterious effects. To enhance the safety, several viral vectors, including vectors based on Sindbis virus, were engineered to lose their capability to replicate and spread after...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.153
更新日期:2009-02-01 00:00:00
abstract::Gene therapy of cystic fibrosis (CF) lung disease needs highly efficient delivery and long-lasting complementation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene into the respiratory epithelium. The development of lentiviral vectors has been a recent advance in the field of gene transfer and th...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302372
更新日期:2004-10-01 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::Genetic engineering of T lymphocytes for adoptive clinical immunotherapy calls for efficient gene transduction methods. Therefore, a transient retroviral gene transduction system 'STITCH' was developed comprising pSTITCH retroviral vector encoding the transgene, plasmids encoding Moloney murine leukemia virus gag/pol ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300696
更新日期:1998-09-01 00:00:00
abstract::We recently showed that the human telomerase reverse transcriptase (hTERT) promoter induces tumor-specific Bax gene expression and selectively kills various human cancer cells both in vitro and in xenograft tumors. However, it remains unclear whether the hTERT promoter can be used to induce transgene expression in syn...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301619
更新日期:2002-01-01 00:00:00