PHASE I TRIAL OF INTRAMUSCULAR INJECTION OF A RECOMBINANT ADENO-ASSOCIATED VIRUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 已经开发了从腺相关病毒（AAV）构建的重组病毒载体，所述腺相关病毒（AAV）已经被改变以携带从具有巨细胞病毒增强子的杂合鸡β肌动蛋白启动子表达的人α 1-抗胰蛋白酶（hAAT）基因。该构建体已显示在与所提出的人体试验紧密匹配的动物模型中启动hAAT的产生。拟议的临床试验是一项开放标签的I期研究，向AAT缺陷型人类受试者肌内施用rAAV 2-CB-hAAT基因载体，其中可以直接在血液样品中测量基因表达，以评估安全性。 安全性参数将是血清化学和血液学、尿分析、肺功能检测、载体基因组的精液测定、对AAT和AAV的免疫应答以及报告的任何症状的受试者病史的变化测量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A recombinant virus vector constructed from adeno associated virus (AAV) that has been altered to carry the human alpha 1-antitrypsin (hAAT) gene expressed from a hybrid chicken beta actin promoter with a cytomegalovirus enhancer has been developed. The construct has been shown to initiate the production of hAAT in animal models closely matching the proposed human trial. The proposed clinical trial is an open label, phase I study administering rAAV2-CB-hAAT gene vector intramuscularly to AAT deficient human subjects where gene expression can be measured directly in blood samples, to assess safety. Safety parameters will be measurement of changes, in serum chemistries and hematology, urinalysis, pulmonary function testing, semen assay for vector genomes, immunologic response to AAT, and AAV, as well as reported subject history of any symptoms.