MULTIVALENT AAV VECTORS FOR HIV-1 GENE THERAPY

该项目将测试以下假设：有能力的腺相关病毒载体 转导非分裂细胞并引导基因表达， 独立的转录单位可以将抗HIV基因转导入 原始自我更新多能造血干细胞在稳定的 时尚.编码各种抗HIV基因的多价AAV载体将被用于治疗HIV感染。 测试了它们对HIV-1的抵抗能力。转导 效率、载体整合和艾滋病毒抗性将在 分化的后代。AAV的长期转录状态 将对载体基因组进行评估，以确定所递送基因的命运 通过AAV载体。本研究旨在提供以下信息： 用AAV载体进行基因转移的基础生物学， 基因治疗的抗病毒疗效、可行性和安全性 使用多价AAV载体在造血干细胞中表达。

This project will test the hypothesis that AAV vectors which are capable of transducing non-dividing cells and directing gene expression from independent transcriptional units can transduce anti-HIV genes into primitive self-renewing pluripotent hematopoietic stem cells in a stable fashion. Multivalent AAV vectors encoding various anti-HIV genes will be tested for their ability to confer resistance to HIV-1. Transduction efficiencies, vector integration and HIV-resistance will be evaluated in the differentiated progeny. The long term transcriptional status of AAV vector genomes will be evaluated to determine the fate of genes delivered by AAV vectors. This study is designed to provide information regarding the basic biology of gene transfer with AAV vectors in addition to the anti-viral efficacy, feasibility and safety of gene therapy of hematopoietic stem cells using multivalent AAV vectors.