Abstract:
:Cytomegalovirus (CMV) promoter is often present in recombinant adenovirus vectors (AdVs) suitable for gene therapy, ensuring high levels of transgene production in a wide range of hosts. Despite this characteristic, the presence of the AdV genome in target cells and tissues typically lasts longer than transgene production that may be rapidly extincted by ill-defined silencing mechanisms. In the present article, it is reported that transcriptionally active drugs, retinoic acid (RA) and histone deacetylase inhibitor trichostatin A (TSA), enhance AdV transgene expression in infected cells and tissues. The association of RA and TSA increased more than seven-fold above control the activity of AdVs encoding for LacZ or VEGF165. This effect was, at least in part, mediated by the direct activation of retinoic acid receptors. Finally, administration of RA and TSA alone at days 0 and 5 after infection prolonged transgene production up to 21 days after infection versus 6-8 days in untreated controls. These results indicate that transcriptionally active drugs improve AdV function and may represent a novel strategy to more efficiently design AdVs for gene therapy interventions.
journal_name
Gene Therjournal_title
Gene therapyauthors
Gaetano C,Catalano A,Palumbo R,Illi B,Orlando G,Ventoruzzo G,Serino F,Capogrossi MCdoi
10.1038/sj.gt.3301296keywords:
subject
Has Abstractpub_date
2000-10-01 00:00:00pages
1624-30issue
19eissn
0969-7128issn
1476-5462journal_volume
7pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, l...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.18
更新日期:2016-05-01 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
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::For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302241
更新日期:2004-07-01 00:00:00
abstract::Schwann cells (SCs) in an injured peripheral nerve form pathways for regenerating axons. Although these cells initially support regeneration, SCs lose their pro-regenerative properties following a prolonged period of denervation. Gene transfer to SC can enhance their therapeutic potential. In this article, we compared...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.47
更新日期:2015-10-01 00:00:00
abstract::Viral therapy of cancer includes strategies such as viral transduction of tumour cells with 'suicide genes', using viral infection to trigger immune-mediated tumour cell death and using oncolytic viruses for their direct anti-tumour action. However, problems still remain in terms of adequate viral delivery to tumours....
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2010.48
更新日期:2010-08-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP-1) is released from neuroendocrine cells in the intestine in the postprandial state and augments glucose-stimulated insulin secretion from pancreatic beta cells. To develop non-beta cells that exhibit physiologically regulated insulin secretion, we coexpressed the GLP-1 receptor and human ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302055
更新日期:2003-09-01 00:00:00
abstract::Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.60
更新日期:2009-09-01 00:00:00
abstract::Intraperitoneal (i.p.) recurrence of cisplatin-refractory and p53 mutant ovarian cancer is a major clinical problem, despite surgery and chemotherapy. dl1520 (ONYX-015) is an E1B-55 kDa gene-deleted adenovirus engineered selectively to replicate in and destroy cancer cells lacking functional p53. However, a correlatio...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301319
更新日期:2000-11-01 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::Gene modification of malignant cells to express immune stimulators (cytokines and immune costimulators) has provided the basis for a novel form of immunotherapy. Using a MPSV-based retroviral vector with hygromycin resistance gene as a selectable marker, we have studied retrovirus-mediated gene transfer of an immune c...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300437
更新日期:1997-07-01 00:00:00
abstract::Advances in islet transplantation have encouraged efforts to create alternative insulin-secreting cells that overcome limitations associated with current therapies. We have recently demonstrated durable correction of murine and porcine diabetes by syngeneic and autologous implantation, respectively, of primary hepatoc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.12
更新日期:2010-05-01 00:00:00
abstract::The ability to restrict gene delivery and expression to particular cell types is of paramount importance for many types of gene therapy, especially in the lung. The alveolar epithelial type I (ATI) cell, in particular, is an attractive cell type to target, as it comprises 95% of the internal surface area of the lung. ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.52
更新日期:2016-10-01 00:00:00
abstract::Urea cycle defects presenting in the neonatal period with hyperammonaemia are associated with high morbidity and mortality, and necessitate liver transplantation for long-term management. Gene therapy is therefore an attractive possibility, with vectors based on adeno-associated virus (rAAV) currently showing exciting...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.51
更新日期:2013-12-01 00:00:00
abstract::Complexes of DNA and cationic lipid offer potential advantages for gene transfer to airway epithelia. However, we found that application of DNA-lipid (DMRIE-DOPE) complexes to primary cultures of human ciliated airway epithelia or explants of rabbit trachea generated only low levels of gene transfer. In contrast, when...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300524
更新日期:1997-11-01 00:00:00
abstract::Deficiency in acid alpha-D-glucosidase results in Pompe's disease. Modified single-stranded oligonucleotide (ODN) was designed to correct the acid alpha-D-glucosidase gene with a C1935 --> A (Asp --> Glu) point mutation which causes a complete loss of enzymatic activity for glycogen digestion in the lysosome. The ODN ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302096
更新日期:2003-10-01 00:00:00
abstract::Mucopolysaccharidosis type IIIA (MPS-IIIA) or Sanfilippo A syndrome is a lysosomal storage genetic disease that results from the deficiency of the N-sulfoglucosamine sulfohydrolase (SGSH) protein, a sulfamidase required for the degradation of heparan sulfate glycosaminoglycans (GAGs). The accumulation of these macromo...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.75
更新日期:2014-12-01 00:00:00
abstract::Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302786
更新日期:2006-10-01 00:00:00
abstract::To facilitate the understanding of the complex process of target gene expression and its control, we report a modified inducible system for activation or repression of target gene expression in response to an exogenously administered compound. The main component of this inducible system is a chimeric transcriptional a...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300402
更新日期:1997-05-01 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::Therapeutic RNA interference (RNAi) has emerged as a promising approach for the treatment of many incurable diseases, including cancer, infectious disease or neurodegenerative disorders. Demonstration of efficacy and safety in animal models is necessary before planning human application. Our group and others have prev...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.10
更新日期:2011-07-01 00:00:00
abstract::Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of P...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.117
更新日期:2010-01-01 00:00:00
abstract::Cancer cachexia, characterized by anorexia, weight loss and progressive tissue wasting, has been postulated to be mediated by various cytokines. However, the precise mechanism of cachexia induction is not fully explained. We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis-elements t...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300819
更新日期:1999-01-01 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::The efficiency with which adenoviral vectors infect airway epithelial cells in vivo is unclear despite extensive preclinical and clinical studies. Our hypothesis is that gene transfer is limited by vector internalization which is mediated by binding of a fiber with a cellular receptor and the RGD motif of the penton b...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::First-generation adenoviral (Ad) vectors are frequently used vectors for experimental and clinical gene transfer. Earlier it has been shown that parallel overexpression of the cell cycle regulator p21(Waf1/Cip1) (p21) or antiapoptotic bcl-2 from a second vector reduces cytotoxicity and improves transgene expression. H...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.2
更新日期:2009-04-01 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::Interferon-alpha (IFN-alpha) or CD80 transduction of tumor cells individually reduces tumorigenicity and enhances antitumor responses. Here, we report that the combination of IFN-alpha and CD80 cancer gene therapy in poorly immunogenic murine tumor models, the colorectal adenocarcinoma cell line MC38, and the methylch...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301034
更新日期:1999-12-01 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::The accessibility of adipose tissue and its ability to secrete various bioactive molecules suggest that adipose cells may be attractive targets for gene therapy applications. Here, we report the use of highly defective herpes simplex virus (HSV) vectors as suitable gene transfer agents for adipose cells in culture and...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302359
更新日期:2005-01-01 00:00:00