A Multi-center, Open-label, Dose-ranging, Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of GLS-6150, Administered ID and Followed by Cellectra® 2000 Healthy Adults and in Persons Previously Treated for Hepatitis C Virus Infection.

Hepatitis C virus (HCV) is an enveloped, single strand, positive sense RNA flavivirus. Infection by HCV is typically chronic, although an estimated
10-20% may spontaneously clear the virus. HCV affects between 1.3 - 2 billion individuals, or 2-3% of the global population. HCV has a seroprevalence of approximately 1% in developed countries such as the US and Korea. Chronic HCV infection leads to hepatic fibrosis and cirrhosis. This Phase I study will evaluate the safety, tolerability and immunogenicity of GLS-6150 administered intradermally (ID) followed by electroporation at 1.0 mg and 2.0 mg/dose assessing 3 and 4-dose regimens.

开始日期2018-09-04

申办/合作机构

GeneOne Life Science, Inc.

[+1]

NCT02027116 / Completed临床1期

Multi-center, Open-label, Dose Escalation, Phase I Trial to Evaluate the Safety, Tolerability and Immunogenicity of VGX-6150 for Second-line Therapy of Chronic Hepatitis C Infection

To evaluate the safety, tolerability and immunogenicity of VGX-6150 as second-line therapy in chronic hepatitis C patients

开始日期2014-01-01

申办/合作机构

GeneOne Life Science, Inc.

[+1]

100 项与 NS3 x HCV NS4B 相关的临床结果

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100 项与 NS3 x HCV NS4B 相关的转化医学

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0 项与 NS3 x HCV NS4B 相关的专利（医药）

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项与 NS3 x HCV NS4B 相关的文献（医药）

2004-04-01·Journal of Virology2区 · 医学

Interactions between Viral Nonstructural Proteins and Host Protein hVAP-33 Mediate the Formation of Hepatitis C Virus RNA Replication Complex on Lipid Raft

2区 · 医学

Article

作者: Gao, Lu ; Lai, Michael M. C. ; Aizaki, Hideki ; He, Jian-Wen

ABSTRACTThe lipid raft membrane has been shown to be the site of hepatitis C virus (HCV) RNA replication. The mechanism of formation of the replication complex is not clear. We show here that the formation of the HCV RNA replication complex on lipid raft (detergent-resistant membranes) requires interactions among the HCV nonstructural (NS) proteins and may be initiated by the precursor of NS4B, which has the intrinsic property of anchoring to lipid raft membrane. In hepatocyte cell lines containing an HCV RNA replicon, most of the other NS proteins, including NS5A, NS5B, and NS3, were also localized to the detergent-resistant membranes. However, when individually expressed, only NS4B was associated exclusively with lipid raft. In contrast, NS5B and NS3 were localized to detergent-sensitive membrane and cytosolic fractions, respectively. NS5A was localized to both detergent-sensitive and -resistant membrane fractions. Furthermore, we show that a cellular vesicle membrane transport protein named hVAP-33 (the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein), which binds to both NS5A and NS5B, plays a critical role in the formation of HCV replication complex. The hVAP-33 protein is partially associated with the detergent-resistant membrane fraction. The expression of dominant-negative mutants and small interfering RNA of hVAP-33 in HCV replicon cells resulted in the relocation of NS5B from detergent-resistant to detergent-sensitive membranes. Correspondingly, the amounts of both HCV RNA and proteins in the cells were reduced, indicating that hVAP-33 is critical for the formation of HCV replication complex and RNA replication. These results indicate that protein-protein interactions among the various HCV NS proteins and hVAP-33 are important for the formation of HCV replication complex.

2004-02-01·RNA3区 · 生物学

Two-step affinity purification of the hepatitis C virus ribonucleoprotein complex

3区 · 生物学

Article

作者: Sarker, Shameema ; Siddiqui, Aleem ; Waris, Gulam

Positive-strand RNA viruses replicate their RNA genome within a ribonucleoprotein (RNP) complex that is associated with cellular membranes. We used a two-step method of purification to isolate hepatitis C virus (HCV) RNP complexes from human hepatoma cell line Huh7, which stably expresses HCV subgenomic replicons. The procedure involved hybridization of replicon-expressing cellular lysates with oligonucleotides tagged with biotin and digoxigenin at their respective termini complementary to subgenomic replicon RNA followed by avidin-agarose enrichment of the mixture and subsequent immunoprecipitation of biotin-eluted material with anti-digoxigenin antibody. The immunoprecipitates were immunoblotted with antisera against HCV nonstructural (NS) proteins. The analysis revealed the association of all the HCV NS proteins (NS3, NS4a, NS4b, NS5a, and NS5b) that are encoded by the subgenomic replicon RNA. The HCV RNP complex migrated in a native polyacrylamide gel with an approximate molecular mass of 450 kD. The association of these viral proteins in the RNP complex reinforces the widely acknowledged notion that RNA viruses accomplish replication within a membranous RNP complex.

1996-08-01·Zhonghua yi xue za zhi

[Establishment of anti-HCV NS5 alpha McAb hybridoma cell lines and its application on clinical immunohistochemical diagnosis].

Article

作者: Lang, Z ; Ji, H ; Gao, J

OBJECTIVETo prepare hybridoma cell lines which secrete anti-HCV recombinant NS5a protein monoclonal antibodies, and to evaluate their usage in investigating the distribution of HCV NS5a antigen in liver tissue.METHODSThe hybridoma cell lines were raised using the conventional protocols. The immunohistochemistry of paraffin embedded liver tissue was performed to determine the distribution of HCV NS5a antigen as well as NS3 antigen in liver tissue.RESULTSFour hybridoma cell lines, which secrete monoclonal antibodies against HCV NS5a protein, were raised and named as 8B2, 6F11, 4C6 and 7D9. They had specific reaction with HCV NS5a protein and had no reaction with HCV core and NS3 proteins. Immunohistochemistry results indicated that 54.8% of anti-HCV positive patient's liver specimens were positive and 70.6% of active cirrhosis positive.CONCLUSIONThe monoclonal antibodies we prepared here are specific to the recombinant HCV NS5 alpha protein and they can be used in the clinical immunohistochemistry diagnosis.