Genetic Vaccines and Therapy最新文献

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Occult HCV or delayed viral clearance from lymphocytes of Chronic HCV genotype 3 patients after interferon therapy. 干扰素治疗后慢性HCV基因型3患者淋巴细胞隐匿性HCV或延迟病毒清除。
Genetic Vaccines and Therapy Pub Date : 2011-09-06 DOI: 10.1186/1479-0556-9-14
Ambreen G Muazzam, Saleem Qureshi, Atika Mansoor, Lubna Ali, Musarrat Iqbal, Saima Siddiqi, Khalid M Khan, Kehkashan Mazhar
{"title":"Occult HCV or delayed viral clearance from lymphocytes of Chronic HCV genotype 3 patients after interferon therapy.","authors":"Ambreen G Muazzam,&nbsp;Saleem Qureshi,&nbsp;Atika Mansoor,&nbsp;Lubna Ali,&nbsp;Musarrat Iqbal,&nbsp;Saima Siddiqi,&nbsp;Khalid M Khan,&nbsp;Kehkashan Mazhar","doi":"10.1186/1479-0556-9-14","DOIUrl":"https://doi.org/10.1186/1479-0556-9-14","url":null,"abstract":"<p><strong>Background: </strong>A recently discovered occult HCV entity reported by various investigators seems to be highly controversial. Especially, the clinical significance of these findings remains uncertain. For optimal outcome of antiviral therapy, investigation of occult HCV needs a broad-based probe in order to investigate the results of viral therapy and its host/viral interaction. The current study was aimed at determining the prevalence of occult HCV in peripheral blood lymphocytes of predominantly genotype 3 HCV-infected patients after completion of antiviral therapy and to investigate long term outcomes in the presence or absence of PBMC positivity.</p><p><strong>Method: </strong>A total of 151 chronic, antiHCV and serum RNA-positive patients were enrolled in the study. Patients with a complete virological response at the end of treatment were screened for the presence of viral RNA in their PBMCs and were followed for up to one year for the presence of serum and PBMC viral genomic RNA.</p><p><strong>Results: </strong>Out of 151 patients, 104 (70%) responded to the prescribed interferon treatment and showed viral-clearance from serum. These were screened for the presence of genomic RNA in their PBMCs. Sixteen samples were PBMC-positive for viral RNA at the end of treatment (EOT). All these patients had also cleared the virus from peripheral blood cells after the 6-12 month follow-up study.</p><p><strong>Conclusion: </strong>True occult hepatitis C virus does not exist in our cohort. Residual viremia at the EOT stage merely reflects a difference in viral kinetics in various compartments that remains a target of immune response even after the end of antiviral therapy and is eventually cleared out at the sustained viral response (SVR).</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"9 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2011-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30119902","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}
引用次数: 9
HCV entry receptors as potential targets for siRNA-based inhibition of HCV. HCV进入受体作为sirna抑制HCV的潜在靶点。
Genetic Vaccines and Therapy Pub Date : 2011-09-06 DOI: 10.1186/1479-0556-9-15
Shah Jahan, Baila Samreen, Saba Khaliq, Bushra Ijaz, Mahwish Khan, Muhammad Hassan Siddique, Waqar Ahmad, Sajida Hassan
{"title":"HCV entry receptors as potential targets for siRNA-based inhibition of HCV.","authors":"Shah Jahan,&nbsp;Baila Samreen,&nbsp;Saba Khaliq,&nbsp;Bushra Ijaz,&nbsp;Mahwish Khan,&nbsp;Muhammad Hassan Siddique,&nbsp;Waqar Ahmad,&nbsp;Sajida Hassan","doi":"10.1186/1479-0556-9-15","DOIUrl":"https://doi.org/10.1186/1479-0556-9-15","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C virus (HCV) is a major health concern with almost 3% of the world's population (350 million individuals) and 10% of the Pakistani population chronically infected with this viral pathogen. The current therapy of interferon-α and ribavirin against HCV has limited efficiency, so alternative options are desperately needed. RNA interference (RNAi), which results in a sequence-specific degradation of HCV RNA has potential as a powerful alternative molecular therapeutic approach. Concerning viral entry, the HCV structural gene E2 is mainly involved in virus attachment to the host cell surface receptors i.e., CD81 tetraspanin, scavenger receptor class B type 1 (SR-B1), low density lipoprotein receptor (LDLR) and claudin1 (CLDN1).</p><p><strong>Results: </strong>In this report, we studied the relationship of the HCV receptors CD81, LDL, CLDN1 and SR-B1to HCV infection. The potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was demonstrated by treatment with siRNAs against HCV receptors, which resulted in a significant decrease in HCV viral copy number.</p><p><strong>Conclusions: </strong>Our data clearly demonstrate that the RNAi-mediated silencing of HCV receptors is among the first of its type for the development of an effective siRNA-based therapeutic option against HCV-3a. These findings will shed further light on the possible role of receptors in inhibition of HCV-3a viral titre through siRNA mediated silencing.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":" ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2011-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29978008","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}
引用次数: 18
Biodistribution and blood clearance of plasmid DNA administered in arginine peptide complexes. 精氨酸肽复合物中质粒DNA的生物分布和血液清除率。
Genetic Vaccines and Therapy Pub Date : 2011-08-17 DOI: 10.1186/1479-0556-9-13
Jung Gyu Woo, Na Young Kim, Jai Myung Yang, Sungho Shin
{"title":"Biodistribution and blood clearance of plasmid DNA administered in arginine peptide complexes.","authors":"Jung Gyu Woo,&nbsp;Na Young Kim,&nbsp;Jai Myung Yang,&nbsp;Sungho Shin","doi":"10.1186/1479-0556-9-13","DOIUrl":"https://doi.org/10.1186/1479-0556-9-13","url":null,"abstract":"<p><strong>Background: </strong>Peptide/DNA complexes have great potential as non-viral methods for gene delivery. Despite promising results for peptide-mediated gene delivery technology, an effective systemic peptide-based gene delivery system has not yet been developed.</p><p><strong>Methods: </strong>This study used pCMV-Luc as a model gene to investigate the biodistribution and the in vivo efficacy of arginine peptide-mediated gene delivery by polymerase chain reaction (PCR).</p><p><strong>Results: </strong>Plasmid DNA was detected in all organs tested 1 h after intraperitoneal administration of arginine/DNA complexes, indicating that the arginine/DNA complexes disseminated widely through the body. The plasmid was primarily detected in the spleen, kidney, and diaphragm 24 h post administration. The mRNA expression of plasmid DNA was noted in the spleen, kidney, and diaphragm for up to 2 weeks, and in the other major organs, for at least 1 week. Blood clearance studies showed that injected DNA was found in the blood as long as 6 h after injection.</p><p><strong>Conclusions: </strong>Taken together, our results demonstrated that arginine/DNA complexes are stable in blood and are effective for in vivo gene delivery. These findings suggest that intraperitoneal administration of arginine/DNA complexes is a promising tool in gene therapy.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":" ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2011-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30083639","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}
引用次数: 4
Establishment of stable Huh-7 cell lines expressing various hepatitis C virus genotype 3a protein: an in-vitro testing system for novel anti-HCV drugs. 表达多种丙型肝炎病毒基因型3a蛋白的稳定Huh-7细胞系的建立:新型抗丙型肝炎药物的体外检测系统
Genetic Vaccines and Therapy Pub Date : 2011-06-28 DOI: 10.1186/1479-0556-9-12
Sadia Butt, Muhammad Idrees, Irshad-Ur Rehman, Liaqat Ali, Abrar Hussain, Muhammad Ali, Naveed Ahmed, Sana Saleem, Madiha Fayyaz
{"title":"Establishment of stable Huh-7 cell lines expressing various hepatitis C virus genotype 3a protein: an in-vitro testing system for novel anti-HCV drugs.","authors":"Sadia Butt,&nbsp;Muhammad Idrees,&nbsp;Irshad-Ur Rehman,&nbsp;Liaqat Ali,&nbsp;Abrar Hussain,&nbsp;Muhammad Ali,&nbsp;Naveed Ahmed,&nbsp;Sana Saleem,&nbsp;Madiha Fayyaz","doi":"10.1186/1479-0556-9-12","DOIUrl":"https://doi.org/10.1186/1479-0556-9-12","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis which progresses to hepatocellular carcinoma (HCC) afflicting > 170 million people worldwide. HCV 3a is the most common genotype (about 70% of all genotypes) circulating in Pakistan. Expression of HCV individual gene of 3a would facilitate therapeutic and vaccines strategies against chronic HCV and liver Cirrhosis. The aim of the present study was the establishment of stable Huh-7 cell lines expressing structural and non structural proteins of HCV Genotype 3a Pakistani isolate obtained from chronic HCV patients.</p><p><strong>Methods: </strong>Blood samples were obtained from chronic HCV-3a positive patients. HCV individual genes were amplified using PCR with gene specific primers having restriction sites. These gene amplicons were cloned in mammalian expression vector PcDNA3.1+. Huh-7 cell lines were transfected with these constructed plasmids having structural or non-structural HCV genes in confluent cells with lipofectamine. Positive clones were selected with G418 and then confirmed by genome PCR. Subsequently, transcription and expression of the integrated genes were demonstrated by RT-PCR, sequencing and Western blot analysis.</p><p><strong>Results: </strong>We successfully cloned and express five HCV-3a genes in PcDNA3.1+ mammalian expression vector. Results of western blot and sequencing PCR confirmed the stable expression of these five genes.</p><p><strong>Conclusion: </strong>The stable cell-lines expressing HCV-3a individual genes would be a useful tool to investigate the role of various HCV proteins on HCV disease outcome and testing of new therapeutic strategies against HCV.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"9 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2011-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29969339","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}
引用次数: 12
Antiviral drugs against hepatitis C virus. 抗丙型肝炎病毒的抗病毒药物。
Genetic Vaccines and Therapy Pub Date : 2011-06-23 DOI: 10.1186/1479-0556-9-11
Sidra Rehman, Usman A Ashfaq, Tariq Javed
{"title":"Antiviral drugs against hepatitis C virus.","authors":"Sidra Rehman,&nbsp;Usman A Ashfaq,&nbsp;Tariq Javed","doi":"10.1186/1479-0556-9-11","DOIUrl":"https://doi.org/10.1186/1479-0556-9-11","url":null,"abstract":"<p><p> Hepatitis C virus (HCV) infection is a major worldwide problem causes acute and chronic HCV infection. Current treatment of HCV includes pegylated interferon-α (PEG IFN- α) plus ribavirin (RBV) which has significant side effects depending upon the type of genotype. Currently, there is a need to develop antiviral agents, both from synthetic chemistry and Herbal sources. In the last decade, various novel HCV replication, helicase and entry inhibitors have been synthesized and some of which have been entered in different phases of clinical trials. Successful results have been acquired by executing combinational therapy of compounds with standard regime in different HCV replicons. Even though, diverse groups of compounds have been described as antiviral targets against HCV via Specifically Targeted Antiviral Therapy for hepatitis C (STAT-C) approach (in which compounds are designed to directly block HCV or host proteins concerned in HCV replication), still there is a need to improve the properties of existing antiviral compounds. In this review, we sum up potent antiviral compounds against entry, unwinding and replication of HCV and discussed their activity in combination with standard therapy. Conclusively, further innovative research on chemical compounds will lead to consistent standard therapy with fewer side effects.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":" ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2011-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30262930","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}
引用次数: 25
Comparative analysis of macrophage associated vectors for use in genetic vaccine. 巨噬细胞相关载体用于基因疫苗的比较分析。
Genetic Vaccines and Therapy Pub Date : 2011-06-18 DOI: 10.1186/1479-0556-9-10
Mohammad Feraz Ahsan, Milind M Gore
{"title":"Comparative analysis of macrophage associated vectors for use in genetic vaccine.","authors":"Mohammad Feraz Ahsan,&nbsp;Milind M Gore","doi":"10.1186/1479-0556-9-10","DOIUrl":"https://doi.org/10.1186/1479-0556-9-10","url":null,"abstract":"<p><strong>Background: </strong>Antigen presentation by non professional antigen presenting cells (APC) can lead to anergy. In genetic vaccines, targeting the macrophages and APC for efficient antigen presentation might lead to balanced immune response. One such approach is to incorporate APC specific promoter in the vector to be used.</p><p><strong>Methods: </strong>Three promoters known to be active in macrophage were selected and cloned in mammalian expressing vector (pAcGFP1-N1) to reconstruct (pAcGFP-MS), (pAcGFP-EMR) and (pAcGFP-B5I) with macrosialin, EmrI and Beta-5 Integrin promoters respectively. As a positive control (pAcGFP-CMV) was used with CMV promoter and promoterless vector (pAcGFP-NIX) which served as a negative control. GFP gene was used as readout under the control of each of the promoter. The expression of GFP was analyzed on macrophage and non-macrophage cell lines using Flow cytometry and qRT-PCR with TaqMan probe chemistries.</p><p><strong>Results: </strong>All the promoters in question were dominant to macrophage lineage cell lines as observed by fluorescence, Western blot and quantitative RT-PCR. The activity of macrosialin was significantly higher than other macrophage promoters. CMV promoter showed 1.83 times higher activity in macrophage cell lines. The expression of GFP driven by macrosialin promoter after 24 hours was 4.40 times higher in macrophage derived cell lines in comparison with non macrophage cell lines.</p><p><strong>Conclusions: </strong>Based on this study, macrosialin promoter can be utilized for targeting macrophage dominant expression. In vivo study needs to be carried out for its utility as a vaccine candidate.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"9 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2011-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29944482","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}
引用次数: 6
A comparison of multiple shRNA expression methods for combinatorial RNAi. 用于组合RNAi的多种shRNA表达方法的比较。
Genetic Vaccines and Therapy Pub Date : 2011-04-17 DOI: 10.1186/1479-0556-9-9
Glen J McIntyre, Allison J Arndt, Kirsten M Gillespie, Wendy M Mak, Gregory C Fanning
{"title":"A comparison of multiple shRNA expression methods for combinatorial RNAi.","authors":"Glen J McIntyre,&nbsp;Allison J Arndt,&nbsp;Kirsten M Gillespie,&nbsp;Wendy M Mak,&nbsp;Gregory C Fanning","doi":"10.1186/1479-0556-9-9","DOIUrl":"10.1186/1479-0556-9-9","url":null,"abstract":"<p><p> RNAi gene therapies for HIV-1 will likely need to employ multiple shRNAs to counter resistant strains. We evaluated 3 shRNA co-expression methods to determine their suitability for present use; multiple expression vectors, multiple expression cassettes and single transcripts comprised of several dsRNA units (aka domains) with each being designed to a different target. Though the multiple vector strategy was effective with 2 shRNAs, the increasing number of vectors required is a major shortcoming. With single transcript configurations we only saw adequate activity from 1 of 10 variants tested, the variants being comprised of 2 - 3 different target domains. Whilst single transcript configurations have the most advantages on paper, these configurations can not yet be rapidly and reliably re-configured for new targets. However, our multiple cassette combinations of 2, 3 and 4 (29 bp) shRNAs were all successful, with suitable activity maintained in all positions and net activities comparable to that of the corresponding single shRNAs. We conclude that the multiple cassette strategy is the most suitably developed for present use as it is easy to design, assemble, is directly compatible with pre-existing shRNA and can be easily expanded.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"9 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2011-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29817817","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}
引用次数: 23
Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism. 改变LCMV假型慢病毒α-三磷酸腺苷受体亲和力产生独特的细胞和组织亲和性。
Genetic Vaccines and Therapy Pub Date : 2011-04-08 DOI: 10.1186/1479-0556-9-8
Douglas E Dylla, Litao Xie, Daniel E Michele, Stefan Kunz, Paul B McCray
{"title":"Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism.","authors":"Douglas E Dylla,&nbsp;Litao Xie,&nbsp;Daniel E Michele,&nbsp;Stefan Kunz,&nbsp;Paul B McCray","doi":"10.1186/1479-0556-9-8","DOIUrl":"https://doi.org/10.1186/1479-0556-9-8","url":null,"abstract":"<p><strong>Background: </strong>The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo.</p><p><strong>Methods: </strong>We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals.</p><p><strong>Results: </strong>In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining.</p><p><strong>Conclusions: </strong>These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer.</p><p><strong>Abbreviations: </strong>Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50).</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":"9 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2011-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9527194","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}
引用次数: 17
In-vitro model systems to study Hepatitis C Virus. 研究丙型肝炎病毒的体外模型系统。
Genetic Vaccines and Therapy Pub Date : 2011-04-06 DOI: 10.1186/1479-0556-9-7
Usman Ali Ashfaq, Shaheen N Khan, Zafar Nawaz, Sheikh Riazuddin
{"title":"In-vitro model systems to study Hepatitis C Virus.","authors":"Usman Ali Ashfaq,&nbsp;Shaheen N Khan,&nbsp;Zafar Nawaz,&nbsp;Sheikh Riazuddin","doi":"10.1186/1479-0556-9-7","DOIUrl":"https://doi.org/10.1186/1479-0556-9-7","url":null,"abstract":"<p><p> Hepatitis C virus (HCV) is a major cause of chronic liver diseases including steatosis, cirrhosis and hepatocellular carcinoma. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. The development of in-vitro models such as HCV infection system, HCV sub-genomic replicon, HCV producing pseudoparticles (HCVpp) and infectious HCV virion provide an important tool to develop new antiviral drugs of different targets against HCV. These models also play an important role to study virus lifecycle such as virus entry, endocytosis, replication, release and HCV induced pathogenesis. This review summarizes the most important in-vitro models currently used to study future HCV research as well as drug design.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":" ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2011-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29795226","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}
引用次数: 25
Double suicide genes driven by kinase domain insert containing receptor promoter selectively kill human lung cancer cells. 含有受体启动子的激酶结构域插入片段驱动双自杀基因选择性杀伤人肺癌细胞。
Genetic Vaccines and Therapy Pub Date : 2011-03-22 DOI: 10.1186/1479-0556-9-6
Junrong Ma, Mi Li, Longyong Mei, Qinghua Zhou, Lunxu Liu, Xijie Yu, Guowei Che
{"title":"Double suicide genes driven by kinase domain insert containing receptor promoter selectively kill human lung cancer cells.","authors":"Junrong Ma,&nbsp;Mi Li,&nbsp;Longyong Mei,&nbsp;Qinghua Zhou,&nbsp;Lunxu Liu,&nbsp;Xijie Yu,&nbsp;Guowei Che","doi":"10.1186/1479-0556-9-6","DOIUrl":"https://doi.org/10.1186/1479-0556-9-6","url":null,"abstract":"<p><strong>Background: </strong>To investigate the selective killing efficacy of the double suicide genes driven by KDR promoter.</p><p><strong>Materials and methods: </strong>A double suicide gene system with the KDR promoter, pcDNA3-KDRp-CDglyTK, was constructed and transfected into lung cancer cell lines L9981 and NL9980, and human hepatocellular carcinoma cell line HepG2. The efficiency and specificity of the double suicide gene system were assayed by in vitro cellular proliferation and apoptosis, as well as in vivo xenograft studies.</p><p><strong>Results: </strong>The transgenic CD and TK genes were only expressed in L9981 and NL9980 but not in HepG2 cells. Pre-treating transfected cells with 5-Fc and GCV significantly reduced proliferation, enhanced apoptosis in L9981 and NL9980 but not in HepG2 cells. The tumor formed by L9981 and NL9980 cells with the double suicide gene system was much smaller in vivo.</p><p><strong>Conclusion: </strong>Tumor targeted expression of CDglyTK gene driven by KDR promotor represents a novel strategy for effective gene therapy of tumor with intrinsic KDR.</p>","PeriodicalId":12596,"journal":{"name":"Genetic Vaccines and Therapy","volume":" ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2011-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1479-0556-9-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29752659","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}
引用次数: 7
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