Gene therapy and regulation最新文献_第7页

Intracoronary gene transfer of fibroblast growth factor in experimental and clinical myocardial ischemia 成纤维细胞生长因子在实验性和临床心肌缺血中的冠状动脉内基因转移

Gene therapy and regulation Pub Date : 2001-12-01 DOI: 10.1163/156855801760107000

H. Hammond

{"title":"Intracoronary gene transfer of fibroblast growth factor in experimental and clinical myocardial ischemia","authors":"H. Hammond","doi":"10.1163/156855801760107000","DOIUrl":"https://doi.org/10.1163/156855801760107000","url":null,"abstract":"An animal model of stress-induced regional myocardial ischemia was used to test the hypothesis that intracoronary delivery of an adenovirus encoding fibroblast growth factor Type 5 (FGF5) would result in improved blood flow, function and neovascularization in the ischemic region of the heart. These data indicated that this approach could be used safely and effectively in resolving regional myocardial ischemia in the ameroid model. Additional unpublished studies confirmed that a similar effect was achievable through use of other angiogenic transgenes, including FGF Type 4 (FGF4). The published studies using direct intracoronary delivery of adenovirus vectors to the heart is reviewed, with a focus on safety and efficacy. A multicenter Phase 1/Phase 2 clinical trial of intracoronary delivery of FGF4 in patients with angina pectoris was initiated under joint sponsorship of Collateral Therapeutics, Incorporated, Berlex Biosciences and Schering AG. Results of this trial are reviewed. The results of this blinded and randomized clinical trial provided data supporting the initiation of two large scale pivotal clinical trials — in the European Union and the US — of intracoronary delivery of adenovirus encoding FGF4 in treating patients with angina.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1163/156855801760107000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64794828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

VEGF gene therapy for chronic critical limb ischemia VEGF基因治疗慢性危重肢体缺血

Gene therapy and regulation Pub Date : 2001-12-01 DOI: 10.1163/156855801760106984

I. Baumgartner

引用次数: 0

Atrial natriuretic peptide gene transfer and regulated expression in primary vascular smooth muscle cells 心房利钠肽基因在原代血管平滑肌细胞中的转移及调控表达

Gene therapy and regulation Pub Date : 2001-08-01 DOI: 10.1163/156855800750367455

M. Wei, Jianping Wang, H. Xia, Qong Li, M. West

{"title":"Atrial natriuretic peptide gene transfer and regulated expression in primary vascular smooth muscle cells","authors":"M. Wei, Jianping Wang, H. Xia, Qong Li, M. West","doi":"10.1163/156855800750367455","DOIUrl":"https://doi.org/10.1163/156855800750367455","url":null,"abstract":"In vitro tests were performed to evaluate the suitability of primary vascular smooth muscle cells (VSMCs) as targets for retroviral vector-mediated atrial natriuretic peptide (ANP) gene transfer, tetracycline (Tet)-regulated expression of ANP transgene and microencapsulation for an ex vivo approach of ANP gene therapy. Rat ANP cDNA was thus cloned from rat atrial tissue, and then sub-cloned and packaged into retroviral vectors comprising standard or Tet-regulated gene expression cassettes. After high efficiency of marker LacZ gene transfer was demonstrated, the expression of immuno-reactive ANP (irANP) was analysed. Our results showed that, unlike non-transduced or LacZ-transduced control VSMCs, LrASN/PA317-transduced VSMCs secreted a significant amount of irANP (425 ± 50 pg/ml/105cells/24 hours, at peak). Importantly enough, LNtetPrtTFrA/PA317-transduced VSMCs were shown to exhibit efficient Tet-regulated expression of irANP with nontoxic concentrations of doxycycline. The biological activity of irANP produced by such engineered VSMCs was evidenced by cyclic GMP (cGMP) activation in LrASN-transduced VSMCs or in VSMCs exposed to conditioned media harvested from VSMCs secreting irANP. Further studies showed that transduced VSMCs synthesised and secreted more irANP than either rat primary endothelial cells, or skin fibroblasts or a transformed mouse fibroblast cell line. Most importantly, micro-encapsulation of engineered VSMCs in alginate did not alter Tet-regulated expression and long-term secretion of irANP. These results suggest that encapsulated engineered VSMCs may prove instrumental in longterm in vivo studies on ANP function and in the development of an ex vivo ANP gene therapy approach for disease states such as hypertension and congestive heart failure.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1163/156855800750367455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64794429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

DNA-based vaccines against malaria and other diseases - from the laboratory to the clinic 针对疟疾和其他疾病的dna疫苗——从实验室到临床

Gene therapy and regulation Pub Date : 2001-08-01 DOI: 10.1163/156855800750367437

D. Doolan, S. Hoffman

引用次数: 2

Adult and embryonic-like stem cells: toward a major gene therapy breakthrough relying on autologous multipotent stem cells 成体和胚胎样干细胞:依赖自体多能干细胞的重大基因治疗突破

Gene therapy and regulation Pub Date : 2001-08-01 DOI: 10.1163/156855800750367428

R. Bertolotti

引用次数: 2

Dual-regulated gene expression in mammalian cells, a novel approach to gene therapy 哺乳动物细胞双调控基因表达:基因治疗的新途径

Gene therapy and regulation Pub Date : 2001-08-01 DOI: 10.1163/156855800750367446

M. Fussenegger

{"title":"Dual-regulated gene expression in mammalian cells, a novel approach to gene therapy","authors":"M. Fussenegger","doi":"10.1163/156855800750367446","DOIUrl":"https://doi.org/10.1163/156855800750367446","url":null,"abstract":"A variety of heterologous mammalian gene regulation systems are currently available for use in human gene therapy and tissue engineering. While individual gene regulation concepts vary significantly in key characteristics (regulation profiles, basal expression levels, human compatibility, immunogenicity, pharmacokinetics and bioavailability of the inducing agent), most of them are sufficiently elaborated to be considered for preclinical research and clinical gene therapy trials. As forefront basic research describes the cell-cycle, differentiation and apoptosis regulatory networks in mammalian cells as an increasingly complex highly interconnected globular regulon, it becomes apparent that many human diseases may originate from the slightest expression imbalances of key regulatory genes. We believe that successful gene therapy of such diseases will involve complex multi-(level) regulated multigene interventions based on a combination of several human-compatible heterologous gene regulation systems which enable optimal integration of therapeutic interventions into the cellular regulon as well as well-balanced expression of several therapeutic transgenes. Although such multiregulated multigene expression scenarios are still a vision, the following are already a scientific reality with cultured cells: (i) combination of two human compatible gene regulation systems to enable dual-regulated expression technology for independent adjustment of two different gene activities, (ii) regulatory cascades for muli-level regulated multigene interventions, and (iii) dual-autoregulated expression configurations for one-step installation of multi-level or reciprocal regulation of heterologous gene expression. This review summarizes pioneering efforts to establish dual-regulated expression technology, a strategy to combine more than one heterologous gene regulation system, to achieve difficult-to-attain cell phenotypes relevant for gene therapy, tissue engineering and basic research.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1163/156855800750367446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64794167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Spliceosome-mediated RNA trans -splicing in gene therapy and genomics 剪接体介导的RNA反式剪接在基因治疗和基因组学中的应用

Gene therapy and regulation Pub Date : 2000-08-15 DOI: 10.1163/156855800744584

M. Garcia-Blanco, M. Puttaraju, S. Mansfield, L. Mitchell

引用次数: 14

MLV-derived retroviral pseudotype vectors mlv衍生的逆转录病毒伪型载体

Gene therapy and regulation Pub Date : 2000-08-15 DOI: 10.1163/156855800744601

J. Stitz, C. Buchholz, K. Cichutek

引用次数: 2

Antiangiogenic gene therapy 抗血管生成基因疗法

Gene therapy and regulation Pub Date : 2000-08-15 DOI: 10.1163/156855800744575

Yihai Cao

{"title":"Antiangiogenic gene therapy","authors":"Yihai Cao","doi":"10.1163/156855800744575","DOIUrl":"https://doi.org/10.1163/156855800744575","url":null,"abstract":"A number of potent endogenous inhibitors targeting the tumor vasculature have recently been identified in tumor-bearing animals. Some of these angiogenesis inhibitors, including angiostatin, endostatin, and serpin antithrombin, seem to act specifically on the proliferating endothelial cells in the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but also provides an important therapeutic strategy for cancer treatment. Several studies have demonstrated that antiangiogenic protein therapy with these inhibitors significantly suppresses the growth of a variety of tumors in mice. However, the dosages of these endogenous inhibitors used in animal studies seem to be too high for clinical trials. Other disadvantages of antiangiogenic protein therapy include repeated injections, prolonged treatment, potential transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative approaches need to be developed in order to improve the antiangiogenic therapy with endogenous inhibitors. Perhaps gene therapy aimed to express these potent angiogenesis inhibitors in vivo is the most promising alternative approach that could transfer antiangiogenic therapy from animal experiments into the clinic. Although the development of this field is still in its early stages, several studies in animals have already provided evidence that this is a promising approach in the treatment of cancer. In this review article, I will discuss the therapeutic potentials of antiangiogenic molecules expressed from gene therapy vectors.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1163/156855800744575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64793470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Targeted inhibition of type I procollagen synthesis by antisense DNA oligonucleotides 反义DNA寡核苷酸对I型前胶原合成的靶向抑制

Gene therapy and regulation Pub Date : 2000-08-15 DOI: 10.1163/156855800744610

Catherine H. Wu, C. Walton, George Y Wu

{"title":"Targeted inhibition of type I procollagen synthesis by antisense DNA oligonucleotides","authors":"Catherine H. Wu, C. Walton, George Y Wu","doi":"10.1163/156855800744610","DOIUrl":"https://doi.org/10.1163/156855800744610","url":null,"abstract":"In hepatic fibrosis, the connective tissue biomatrix of the liver changes from the normal matrix, rich in basement membrane collagens, to a matrix enriched in interstitial fibrillar collagens. Type I collagen is the predominant component of thick fibrous bands found in matrix in advanced fibrosis. The aim of the current research was to determine whether a therapeutic approach could be developed that would specifically target collagen-producing cells to reduce the synthesis and accumulation of type I collagen. Antisense DNA oligonucleotides directed against specific sequences within α1(I) and α2(I) mRNA of type I procollagen were complexed to a cell-specific carrier, and screened for their effectiveness in reducing α1(I) and α2(I) mRNA levels. Two antisense DNA oligonucleotides delivered by the carrier were found to be most effective in reducing α1(I) and α2(I) mRNA and total collagen accumulation in the cells, but had no effect on reducing β-actin mRNA in the same cells. At similar concentrations, free antisense DNA oligonucleotides were not effective in inhibiting collagen synthesis, and/or in decreasing cellular concentrations of α1(I) or α2(I) mRNA. Collagen synthesis and mRNA levels in cells lacking receptors that recognize the carrier protein were not changed after treatment with complexed antisense DNA. The results indicate that antisense oligonucleotides can be targeted to cell types, and were effective inhibiting collagen synthesis in those cells.","PeriodicalId":93646,"journal":{"name":"Gene therapy and regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1163/156855800744610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64793686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4