Genetic Vaccines and Therapy最新文献

{"title":"A combined nucleocapsid vaccine induces vigorous SARS-CD8+ T-cell immune responses.","authors":"Ali Azizi,&nbsp;Susan Aucoin,&nbsp;Helina Tadesse,&nbsp;Rita Frost,&nbsp;Masoud Ghorbani,&nbsp;Catalina Soare,&nbsp;Turaya Naas,&nbsp;Francisco Diaz-Mitoma","doi":"10.1186/1479-0556-3-7","DOIUrl":"https://doi.org/10.1186/1479-0556-3-7","url":null,"abstract":"<p><p>Several studies have shown that cell-mediated immune responses play a crucial role in controlling viral replication. As such, a candidate SARS vaccine should elicit broad CD8+ T-cell immune responses. Several groups of mice were immunized alone or in combination with SARS-nucleocapsid immunogen. A high level of specific SARS-CD8+ T-cell response was demonstrated in mice that received DNA encoding the SARS-nucleocapsid, protein and XIAP as an adjuvant. We also observed that co-administration of a plasmid expressing nucleocapsid, recombinant protein and montanide/CpG induces high antibody titers in immunized mice. Moreover, this vaccine approach merits further investigation as a potential candidate vaccine against SARS.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"3 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2005-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-3-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25261211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing the epidermal growth factor receptor gene with RNAi may be developed as a potential therapy for non small cell lung cancer.","authors":"Min Zhang,&nbsp;Xin Zhang,&nbsp;Chun-Xue Bai,&nbsp;Xian-Rang Song,&nbsp;Jie Chen,&nbsp;Lei Gao,&nbsp;Jie Hu,&nbsp;Qun-Ying Hong,&nbsp;Malcolm J West,&nbsp;Ming Q Wei","doi":"10.1186/1479-0556-3-5","DOIUrl":"https://doi.org/10.1186/1479-0556-3-5","url":null,"abstract":"<p><p>Lung cancer has emerged as a leading cause of cancer death in the world. Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers. Current therapies are ineffective, thus new approaches are needed to improve the therapeutic ratio. Double stranded RNA (dsRNA)-mediated RNA interference (RNAi) has shown promise in gene silencing, the potential of which in developing new methods for the therapy of NSCLC needs to be tested. We report here RNAi induced effective silencing of the epidermal growth factor receptor (EGFR) gene, which is over expressed in NSCLC. NSCLC cell lines A549 and SPC-A1 were transfected with sequence- specific dsRNA as well as various controls. Immune fluorescent labeling and flow cytometry were used to monitor the reduction in the production of EGFR protein. Quantitative reverse-transcriptase PCR was used to detect the level of EGFR mRNA. Cell count, colony assay, scratch assay, MTT assay in vitro and tumor growth assay in athymic nude mice in vivo were used to assess the functional effects of EGFR silencing on tumor cell growth and proliferation. Our data showed transfection of NSCLC cells with dsRNA resulted in sequence specific silencing of EGFR with 71.31% and 71.78 % decreases in EGFR protein production and 37.04% and 54.92% in mRNA transcription in A549 and SPC-A1 cells respectively. The decrease in EGFR protein production caused significant growth inhibition, i.e.: reducing the total cell numbers by 85.0% and 78.3%, and colony forming numbers by 63.3% and 66.8%. These effects greatly retarded the migration of NSCLC cells by more than 80% both at 24 h and at 48 h, and enhanced chemo-sensitivity to cisplatin by four-fold in A549 cells and seven-fold in SPC-A1. Furthermore, dsRNA specific for EGFR inhibited tumor growth in vivo both in size by 75.06% and in weight by 73.08%. Our data demonstrate a new therapeutic effect of sequence specific suppression of EGFR gene expression by RNAi, enabling inhibition of tumor proliferation and growth. However, in vivo use of dsRNA for gene transfer to tumor cells would be limited because dsRNA would be quickly degraded once delivered in vivo. We thus tested a new bovine lentiviral vector and showed lentivector-mediated RNAi effects were efficient and specific. Combining RNAi with this gene delivery system may enable us to develop RNAi for silencing EGFR into an effective therapy for NSCLC.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"3 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2005-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-3-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25163369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immediate transfection of patient-derived leukemia: a novel source for generating cell-based vaccines.","authors":"Jill A Gershan,&nbsp;Bryon D Johnson,&nbsp;James Weber,&nbsp;Dennis W Schauer,&nbsp;Natalia Natalia,&nbsp;Stephanie Behnke,&nbsp;Karen Burns,&nbsp;Kelly W Maloney,&nbsp;Anne B Warwick,&nbsp;Rimas J Orentas","doi":"10.1186/1479-0556-3-4","DOIUrl":"https://doi.org/10.1186/1479-0556-3-4","url":null,"abstract":"<p><strong>Background: </strong>The production of cell-based cancer vaccines by gene vectors encoding proteins that stimulate the immune system has advanced rapidly in model systems. We sought to develop non-viral transfection methods that could transform patient tumor cells into cancer vaccines, paving the way for rapid production of autologous cell-based vaccines.</p><p><strong>Methods: </strong>As the extended culture and expansion of most patient tumor cells is not possible, we sought to first evaluate a new technology that combines electroporation and chemical transfection in order to determine if plasmid-based gene vectors could be instantaneously delivered to the nucleus, and to determine if gene expression was possible in a cell-cycle independent manner. We tested cultured cell lines, a primary murine tumor, and primary human leukemia cells from diagnostic work-up for transgene expression, using both RFP and CD137L expression vectors.</p><p><strong>Results: </strong>Combined electroporation-transfection directly delivered plasmid DNA to the nucleus of transfected cells, as demonstrated by confocal microscopy and real-time PCR analysis of isolated nuclei. Expression of protein from plasmid vectors could be detected as early as two hours post transfection. However, the kinetics of gene expression from plasmid-based vectors in tumor cell lines indicated that optimal gene expression was still dependent on cell division. We then tested to see if pediatric acute lymphocytic leukemia (ALL) would also display the rapid gene expression kinetics of tumor cells lines, determining gene expression 24 hours after transfection. Six of 12 specimens showed greater than 17% transgene expression, and all samples showed at least some transgene expression.</p><p><strong>Conclusion: </strong>Given that transgene expression could be detected in a majority of primary tumor samples analyzed within hours, direct electroporation-based transfection of primary leukemia holds the potential to generate patient-specific cancer vaccines. Plasmid-based gene therapy represents a simple means to generate cell-based cancer vaccines and does not require the extensive infrastructure of a virus-based vector system.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"3 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2005-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-3-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25148021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax.","authors":"Stuart D Perkins,&nbsp;Helen C Flick-Smith,&nbsp;Helen S Garmory,&nbsp;Angela E Essex-Lopresti,&nbsp;Freda K Stevenson,&nbsp;Robert J Phillpotts","doi":"10.1186/1479-0556-3-3","DOIUrl":"https://doi.org/10.1186/1479-0556-3-3","url":null,"abstract":"<p><p>BACKGROUND: Previously, antigens expressed from DNA vaccines have been fused to the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy. However, the immune enhancing mechanism of VP22 is poorly understood and initial suggestions that VP22 can mediate intercellular spread have been questioned. Despite this, fusion of VP22 to antigens expressed from DNA vaccines has improved immune responses, particularly to non-secreted antigens. METHODS: In this study, we fused the gene for the VP22 protein to the gene for Protective Antigen (PA) from Bacillus anthracis, the causative agent of anthrax. Protective immunity against infection with B. anthracis is almost entirely based on a response to PA and we have generated two constructs, where VP22 is fused to either the N- or the C-terminus of the 63 kDa protease-cleaved fragment of PA (PA63). RESULTS: Following gene gun immunisation of A/J mice with these constructs, we observed no improvement in the anti-PA antibody response generated. Following an intraperitoneal challenge with 70 50% lethal doses of B. anthracis strain STI spores, no difference in protection was evident in groups immunised with the DNA vaccine expressing PA63 and the DNA vaccines expressing fusion proteins of PA63 with VP22. CONCLUSION: VP22 fusion does not improve the protection of A/J mice against live spore challenge following immunisation of DNA vaccines expressing PA63.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"3 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2005-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-3-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25067896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroporation by nucleofector is the best nonviral transfection technique in human endothelial and smooth muscle cells.","authors":"Nina Iversen,&nbsp;Baard Birkenes,&nbsp;Kari Torsdalen,&nbsp;Srdjan Djurovic","doi":"10.1186/1479-0556-3-2","DOIUrl":"https://doi.org/10.1186/1479-0556-3-2","url":null,"abstract":"<p><p>BACKGROUND: The aim of this study was to determine the optimal non-viral transfection method for use in human smooth muscle cells (SMC) and endothelial cells (EC). METHODS: Coronary Artery (CoA) and Aortic (Ao) SMC and EC were transfected with a reporter plasmid, encoding chloramphenicol acetyltransferase type 1 (CAT), with seven different transfection reagents, two electroporation methods and a photochemical internalization (PCI) method. CAT determination provided information regarding transfection efficiency and total protein measurement was used to reflect the toxicity of each method. RESULTS: Electroporation via the nucleofector machine was the most effective method tested. It exhibited a 10 to 20 fold (for SMC and EC, respectively) increase in transfection efficiency in comparison to the lipofection method combined with acceptable toxicity. FuGene 6 and Lipofectamine PLUS were the preferred transfection reagents tested and resulted in 2 to 60 fold higher transfection efficiency in comparison to the PCI which was the least effective method. CONCLUSION: This study indicates that electroporation via the nucleofector machine is the preferred non-viral method for in vitro transfection of both human aortic and coronary artery SMC and EC. It may be very useful in gene expression studies in the field of vascular biology. Through improved gene transfer, non-viral transfer techniques may also play an increasingly important role in delivering genes to SMC and EC in relevant disease states.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"3 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2005-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-3-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25234824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cytomegalovirus plasmid-based amplicon vector system for gene therapy.","authors":"Kutubuddin Mahmood,&nbsp;Mark N Prichard,&nbsp;Gregory M Duke,&nbsp;George W Kemble,&nbsp;Richard R Spaete","doi":"10.1186/1479-0556-3-1","DOIUrl":"https://doi.org/10.1186/1479-0556-3-1","url":null,"abstract":"<p><p>We have constructed and evaluated the utility of a helper-dependent virus vector system that is derived from Human Cytomegalovirus (HCMV). This vector is based on the herpes simplex virus (HSV) amplicon system and contains the HCMV orthologs of the two cis-acting functions required for replication and packaging of HSV genomes, the complex HCMV viral DNA replication origin (oriLyt), and the cleavage packaging signal (the a sequence). The HCMV amplicon vector replicated independently and was packaged into infectious virions in the presence of helper virus. This vector is capable of delivering and expressing foreign genes in infected cells including progenitor cells such as human CD34+ cells. Packaged defective viral genomes were passaged serially in fibroblasts and could be detected at passage 3; however, the copy number appeared to diminish upon serial passage. The HCMV amplicon offers an alternative vector strategy useful for gene(s) delivery to cells of the hematopoietic lineage.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"3 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2005-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-3-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24924462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA vaccines: designing strategies against parasitic infections.","authors":"Catherine Ivory,&nbsp;Kris Chadee","doi":"10.1186/1479-0556-2-17","DOIUrl":"https://doi.org/10.1186/1479-0556-2-17","url":null,"abstract":"<p><p>The complexity of parasitic infections requires novel approaches to vaccine design. The versatility of DNA vaccination provides new perspectives. This review discusses the use of prime-boost immunizations, genetic adjuvants, multivalent vaccines and codon optimization for optimal DNA vaccine design against parasites.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"2 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2004-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-2-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24844760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vivo</i> gene targeting of IL-3 into immature hematopoietic cells through CD117 receptor mediated antibody gene delivery.","authors":"Alain Chapel,&nbsp;Olivier Deas,&nbsp;Morad Bensidhoum,&nbsp;Sabine François,&nbsp;Moubarak Mouiseddine,&nbsp;Pascal Poncet,&nbsp;Antoine Dürrbach,&nbsp;Jocelyne Aigueperse,&nbsp;Patrick Gourmelon,&nbsp;Norbert C Gorin,&nbsp;François Hirsch,&nbsp;Dominique Thierry","doi":"10.1186/1479-0556-2-16","DOIUrl":"https://doi.org/10.1186/1479-0556-2-16","url":null,"abstract":"<p><strong>Background: </strong>Targeted gene transfection remains a crucial issue to permit the real development of genetic therapy. As such, <i>in vivo</i> targeted transfection of specific subsets of hematopoietic stem cells might help to sustain hematopoietic recovery from bone marrow aplasia by providing local production of growth factors.</p><p><strong>Methods: </strong>Balb/C mice were injected intravenously, with an anti-mouse c-kit (CD117) monoclonal antibody chemically coupled to a human IL-3 gene-containing plasmid DNA. Mice were sacrificed for tissue analyses at various days after injection of the conjugates.</p><p><strong>Results: </strong>By ELISA, the production of human IL-3 was evidenced in the sera of animals 5 days after treatment. Cytofluorometric analysis after <i>in vivo</i> transfection of a reporter gene eGFP demonstrated transfection of CD117+/Sca1+ hematopoietic immature cells. By PCR analysis of genomic DNA and RNA using primer specific pIL3 sequences, presence and expression of the human IL-3-transgene were detected in the bone marrow up to 10 days in transfected mice but not in control animals.</p><p><strong>Conclusions: </strong>These data clearly indicate that antibody-mediated endocytosis gene transfer allows the expression of the IL-3 transgene into hematopoietic immature cells, <i>in vivo</i>. While availability of marketed recombinant growth factors is restricted, this targeting strategy should permit delivery of therapeutic genes to tissues of interest through systemic delivery. In particular, the ability to specifically target growth factor expression into repopulating hematopoietic stem cells may create new opportunities for the treatment of primary or radiation-induced marrow failures.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"2 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2004-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-2-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24782833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of recombinant adenovirus-mediated expression of IL-2 and IL-12 in human B lymphoma cells on co-cultured PBMC.","authors":"Oliver Ebert,&nbsp;Dorothee Wilbert,&nbsp;Peter Buttgereit,&nbsp;Carsten Ziske,&nbsp;Dimitri Flieger,&nbsp;Ingo Gh Schmidt-Wolf","doi":"10.1186/1479-0556-2-15","DOIUrl":"https://doi.org/10.1186/1479-0556-2-15","url":null,"abstract":"<p><p>BACKGROUND: Modulation of the immune system by genetically modified lymphoma cell vaccines is of potential therapeutic value in the treatment of B cell lymphoma. However, the anti-tumor effect of any single immunogene transfer has so far been limited. Combination treatment of recombinant IL-2 and IL-12 has been reported to be synergistic for inducing anti-tumor responses in solid tumors but the potential of IL-2/IL-12 gene modified B cell lymphoma cells has not been explored yet. METHODS: Using three different human B cell lymphoma cell lines and primary samples from patients with B cell neoplasms, expression levels of the coxsackie B-adenovirus receptor (CAR) and alpha (v) integrins were analyzed by fluorescence-activated cell sorter (FACS). Adenoviral transduction efficiencies were determined by GFP expression analysis and IL-2 and IL-12 cytokine production was quantified by enzyme-linked immunosorbent (ELISA) assays. Proliferative activities of peripheral blood mononuclear cells (PBMC) stimulated with either cytokine derived from supernatants of transduced lymphoma cells were measured by cell proliferation (MTT) assays. An EuTDA cytotoxicity assay was used to compare cytotoxic activities of IL-2 and/or IL-12 stimulated PBMC against unmodified lymphoma cells. RESULTS: We found that B cell lymphoma cell lines could be transduced with much higher efficiency than primary tumor samples, which appeared to correlate with the expression of CAR. Adenoviral-expressed IL-2 and IL-12 similarly led to dose-dependent increases in proliferation rates of PBMC obtained from healthy donors. IL-2 and/or IL-12 transduced lymphoma cells were co-cultured with PBMC, which were assayed for their cytolytic activity against unmodified lymphoma cells. We found that IL-2 stimulated PBMC elicited a significant anti-tumor effect but not the combined effect of IL-2/IL-12 or IL-12 alone. CONCLUSION: This study demonstrates that the generation of recombinant adenovirus modified lymphoma cell vaccines based on lymphoma cell lines expressing IL-2 and IL-12 cytokine genes is technically feasible, induces increases in proliferation rates and cytotoxic activity of co-cultured PBMC, and warrants further development for the treatment of lymphoma patients in the future.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":" ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2004-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-2-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40919428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved gene delivery to human saphenous vein cells and tissue using a peptide-modified adenoviral vector.","authors":"Lorraine M Work,&nbsp;Paul N Reynolds,&nbsp;Andrew H Baker","doi":"10.1186/1479-0556-2-14","DOIUrl":"https://doi.org/10.1186/1479-0556-2-14","url":null,"abstract":"<p><p>The establishment of efficient gene delivery to target human tissue is a major obstacle for transition of gene therapy from the pre-clinical phases to the clinic. The poor long-term patency rates for coronary artery bypass grafting (CABG) is a major clinical problem that lacks an effective and proven pharmacological intervention. Late vein graft failure occurs due to neointima formation and accelerated atherosclerosis. Since CABG allows a clinical window of opportunity to genetically modify vein ex vivo prior to grafting it represents an ideal opportunity to develop gene-based therapies. Adenoviral vectors have been frequently used for gene delivery to vein ex vivo and pre-clinical studies have shown effective blockade in neointima development by overexpression of candidate therapeutic genes. However, high titers of adenovirus are required to achieve sufficient gene delivery to provide therapeutic benefit. Improvement in the uptake of adenovirus into the vessel wall would therefore be of benefit. Here we determined the ability of an adenovirus serotype 5 vector genetically-engineered with the RGD-4C integrin targeting peptide inserted into the HI loop (Ad-RGD) to improve the transduction of human saphenous vein smooth muscle cells (HSVSMC), endothelial cells (HSVEC) and intact saphenous vein compared to a non-modified virus (Ad-CTL). We exposed each cell type to virus for 10, 30 or 60 mins and measured transgene at 24 h post infection. For both HSVSMC and HSVEC Ad-RGD mediated increased transduction, with the largest increases observed in HSVSMC. When the experiments were repeated with intact human saphenous vein (the ultimate clinical target for gene therapy), again Ad-RGD mediated higher levels of transduction, at all clinically relevant exposures times (10, 30 and 60 mins tissue:virus exposure). Our study demonstrates the ability of peptide-modified Ad vectors to improve transduction to human vein graft cells and tissue and has important implications for gene therapy for CABG.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":" ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2004-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-2-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40910330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}