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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。用腺相关病毒(AAV)构建了携带人α1-抗胰蛋白酶(HAAT)基因的重组病毒载体，该基因由鸡β肌动蛋白启动子和巨细胞病毒增强子杂交而成。该结构已被证明在与拟议的人体试验非常接近的动物模型中启动了HAAT的生产。拟议的临床试验是一项开放式标签的第一阶段研究，研究将rAAV2-CB-HAAT基因载体肌肉注射到AAT缺陷的受试者，在这种情况下，可以直接在血液样本中测量基因表达，以评估安全性。安全参数将包括血清化学和血液学、尿液分析、肺功能测试、载体基因组精液分析、对AAT和AAV的免疫学反应以及报告的任何症状的受试者病史的变化。

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.