CHIMERIC ADENO/AVV VECTOR FOR GENE THERAPY AGAINST HCV

用于 HCV 基因治疗的嵌合腺苷/AVV 载体

• 批准号: 2643928
• 负责人: JACK R BARBER
• 金额: $ 10万
• 依托单位: ITHERX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2643928
• 关键词: Adenoviridae; adeno associated virus group; chimeric proteins; gene expression; gene therapy; hepatitis C; hepatitis C virus; plasmids; polylysine; protein engineering; ribozymes; transfection; transfection /expression vector; virus RNA

DESCRIPTION (adapted from investigator's abstract): Immusol, Inc., has created two ribozymes, CR2 and CR4, that efficiently cleave hepatitis C virus (HCV) RNA is hepatocyte culture. In order to achieve high level stable expression of these ribozymes for HCV gene therapy, Immusol will develop a novel chimeric adenovirus-based vector system that incorporates adeno-associated virus (AAV) inverted terminal repeats (ITR). The chimeric vector will be able to grow to high titer and will be efficient at transducing hepatocyte cells. The presence of AAV ITRs will mediate the integration and stable expression of the transgene(s) in the transduced cells. To increase the efficiency of transgene integration, established techniques will be used to conjugate an AAV replication gene-expressing plasmid to the chimeric virus particles by polylysine. In addition, chimeric vectors will be tested which transiently express rep protein. The effectiveness of CR2 and CR4 ribozymes in chimeric vectors against HCV RNA will be tested in a hepatocyte culture system. After a successful phase I in vitro study, the applicant proposes to initiate an SBIR phase II animal study for the effectiveness of the ribozymes in inhibiting HCV replication and a phase I clinical trial with HCV-infected patients using ribozymes delivered by an adenovirus-AAV chimeric vector. PROPOSED COMMERCIAL APPLICATION: Potential commercial application not available.

描述（改编自研究者摘要）：Immusol，Inc.，具有 创造了两种核酶，CR2和CR 4，可以有效地切割丙型肝炎病毒， HCV RNA是肝细胞培养物。为了达到高水平 为了稳定表达这些用于HCV基因治疗核酶，Immusol将 开发一种新的嵌合腺病毒载体系统， 腺相关病毒（腺相关病毒）反向末端重复序列（ITR）。嵌合 载体将能够生长到高滴度，并且将有效地 转导肝细胞。AAV ITR的存在将介导细胞的增殖。 转基因在转导细胞中的整合和稳定表达 细胞为了提高转基因整合的效率，建立了 技术将用于缀合AAV复制基因表达载体， 通过多聚赖氨酸将质粒连接到嵌合病毒颗粒上。此外，本发明还提供了一种方法， 将测试瞬时表达REP蛋白的嵌合载体。的 CR2和CR 4核酶在抗HCV RNA嵌合载体中作用 将在肝细胞培养系统中进行测试。在第一阶段成功后， 在体外研究中，申请人建议启动SBIR II期动物 核酶抑制丙型肝炎病毒复制的研究 以及使用核酶对HCV感染患者进行的I期临床试验 通过腺病毒-AAV嵌合载体递送。 拟定商业应用： 潜在的商业应用不可用。