PERIPHERAL BLOOD STEM CELLS AS TARGETS FOR GENE THERAPY

不能转导足够部分的干细胞 池是镰状细胞疾病基因治疗的一个主要限制因素 痛苦和虚弱的血液疾病，折磨着大约1/4的人 每1000名非洲裔美国人。在这个项目中，我们是 确定动员造血干细胞的最佳条件 从骨髓进入外周血的细胞是最大的 可以收获的干细胞数量。我们也在调查 体外转导这些细胞进行校正的最佳条件 镰状细胞或其他细胞中的遗传缺陷 血红蛋白疾病。我们已经发现，来自 不同种类的非人类灵长类动物在能力上存在差异 用我们的逆转录病毒载体进行转导。

The inability to transduce a sufficient fraction of the stem cell pool is a major limitation of gene therapy for sickle cell disease, a painful and debilitating blood disorder that afflicts about one in every 1000 Americans of African descent. In this project we are identifying the optimal conditions for mobilizing hemopoietic stem cells from the bone marrow into the peripheral blood so the greatest number of stem cells can be harvested. We are also investigating optimal conditions for transduction of these cells ex vivo to correct the genetic defect in the sickle cell or in cells from other hemoglobin diseases. We have found that the stem cells from the different species of nonhuman primates vary in their ability to be transduced with our retroviral constructs.