CHIMERIC ADENO/AVV VECTOR FOR GENE THERAPY AGAINST HCV

描述(改编自调查人员摘要)：Immusol，Inc. 产生了两种核酶，CR2和CR4，可以有效地切割丙型肝炎 丙型肝炎病毒核糖核酸是肝细胞培养。为了达到高水平 这些核酶的稳定表达将用于丙型肝炎病毒的基因治疗 开发一种新型嵌合腺病毒载体系统 腺相关病毒(AAV)反向末端重复序列(ITR)。嵌合者 载体将能够生长到高滴度，并将在 转导肝细胞。AAV ITR的存在将调解 外源基因(S)在转基因植物中的整合与稳定表达 细胞。为了提高转基因整合的效率，建立了 技术将被用来结合AAV复制基因表达 通过多聚赖氨酸将质粒转化为嵌合病毒颗粒。此外, 将对瞬时表达rep蛋白的嵌合载体进行测试。这个 CR2和CR4核酶在嵌合载体中抗丙型肝炎病毒RNA的效果 将在肝细胞培养系统中进行测试。在第一阶段取得成功后 在体外研究中，申请人提议启动SBIR II期动物 核酶抑制丙型肝炎病毒复制效果的研究 以及使用核酶对丙型肝炎病毒感染者进行的I期临床试验 通过腺病毒-AAV嵌合载体传递。 建议的商业应用： 潜在的商业应用程序不可用。

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.