New HCV isolates SBIR

新 HCV 分离出 SBIR

• 批准号: 7231275
• 负责人: VICTOR E. BUCKWOLD
• 金额: $ 10万
• 依托单位: VERACITY BIOTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231275
• 关键词: ADAR1; Adenosine Deaminase Inhibitor; Agreement; Antiviral Agents; Antiviral Therapy; Biological Assay; Biotechnology; Cell Line; Cells; Chronic Hepatitis; Client; Clinical; Clinical Trials; Double-Stranded RNA; Drug resistance; Evaluation; Funding; Generations; Genotype; Hepatitis C; Hepatitis C virus; In Vitro; Infection; Infectious hepatitides; Interferons; Lead; Legal patent; Licensing; Pathway interactions; Patients; Phase; Protocols documentation; Public Health; Reagent; Replicon; Research; Research Contracts; Sampling; Serum; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Technology; Testing; United States; United States Food and Drug Administration; United States National Institutes of Health; Vaccines; Viral; Virus; base; drug development; eIF-2 Kinase; research study; response; success; tissue culture; viral RNA; virus culture

DESCRIPTION (provided by applicant): Infection with the hepatitis C virus (HCV) is the most common cause of chronic hepatitis in the United States. HCV is classified into one of six different genotypes, each composed of a variety of related subtypes. One of the most important predictors of the response of patients to antiviral therapy for HCV infection is viral genotype. Currently, infectious HCV that are able to replicate autonomously in tissue culture are available only for genotypes 1a, 1b and 2a. This application aims to create cell lines that are persistently-infected with new isolates of HCV for drug development applications. Our strategy is based on the use of a licensed technology that increases the replicative ability of HCV in tissue culture. We will try to infect various cell lines with six clinical samples containing various isolates of HCV by using this technology. Partial success will be defined as the isolation of a cell line persistently-infected with a new genotype or subtype of HCV that can be used for antiviral evaluation assays. Complete project success will be indicated by our ability to culture all of the clinical samples of HCV utilized. If the HCV found in clinical samples can be propagated in vitro, then a true phenotypic assay of drug resistance in clinical samples could be developed. Our efforts will ultimately help expedite drug development for HCV, leading to improvements in Public Health. One of the most important predictors of the response of patients to antiviral therapy for hepatitis C virus (HCV) infection is viral genotype. Currently, only three isolates of HCV that can replicate in tissue culture are available. This SBIR application aims to create cell lines that are persistently- infected with new clinical isolates of HCV. If the HCV found in clinical samples can be propagated in vitro, then other viral genotypes could be used during drug development and a true phenotypic assay of drug resistance in clinical samples could be developed. This would help expedite drug development for HCV, leading to improvements in Public Health.

描述（由申请人提供）：丙型肝炎病毒（HCV）感染是美国慢性肝炎的最常见原因。 HCV 分为六种不同基因型之一，每种基因型由多种相关亚型组成。患者对抗 HCV 感染抗病毒治疗反应的最重要预测因素之一是病毒基因型。目前，能够在组织培养中自主复制的传染性HCV仅适用于基因型1a、1b和2a。该应用旨在创建持续感染 HCV 新分离株的细胞系，用于药物开发应用。我们的策略基于使用许可技术来提高组织培养中 HCV 的复制能力。我们将尝试利用该技术用含有各种HCV分离株的六种临床样本感染各种细胞系。部分成功将被定义为分离出持续感染HCV新基因型或亚型的细胞系，该细胞系可用于抗病毒评估测定。我们有能力培养所用的所有 HCV 临床样本，这将表明项目的成功。如果临床样本中发现的丙型肝炎病毒可以在体外繁殖，那么就可以开发出临床样本中耐药性的真正表型测定方法。我们的努力最终将有助于加快丙肝病毒药物的开发，从而改善公共卫生。 患者对抗丙型肝炎病毒（HCV）感染的抗病毒治疗反应的最重要预测因素之一是病毒基因型。目前，只有三种可在组织培养中复制的 HCV 分离株可用。该 SBIR 应用旨在创建持续感染新的 HCV 临床分离株的细胞系。如果临床样本中发现的 HCV 可以在体外繁殖，那么在药物开发过程中就可以使用其他病毒基因型，并且可以开发临床样本中耐药性的真实表型测定。这将有助于加快丙肝病毒药物的开发，从而改善公共卫生。