PERIPHERAL BLOOD STEM CELLS AS TARGETS FOR GENE THERAPY

镰状细胞病是一种痛苦的、使人衰弱的血液疾病，每1000名非洲裔美国人中就有1人患有这种疾病。在这个项目中，我们正在确定将造血干细胞从骨髓转移到外周血的最佳条件，以便获得最多数量的干细胞。我们也在研究这些细胞在体外转导的最佳条件，以纠正镰状细胞或其他血红蛋白疾病细胞中的遗传缺陷。我们已经发现，来自不同种类的非人灵长类动物的干细胞在用我们的逆转录病毒构建体转导的能力上是不同的。

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.