STEM CELL THERAPY OF CONGENITAL DEFECTS IN HEMATOPOIESIS

这项SCOR建议的总体目标是开发和进行临床试验，以纠正人类造血干细胞的先天性疾病。研究计划的中心主题是开发治疗这些疾病的细胞和转导基因治疗的新方法。具体地说，我们将开发跨越人类白细胞抗原屏障的干细胞移植的新方法，并将尝试通过替代基因治疗方案来治疗范科尼贫血和钻石-布莱克凡贫血。Guinan博士的项目将集中在单倍体相合骨髓移植的生物学和临床方面的新进展。几个项目将侧重于Fanconi贫血和钻石-Blackfan贫血的基础生物学，以及用于骨髓移植的逆转录病毒转基因扩大和I期基因治疗方案。其他项目将侧重于逆转录病毒和慢病毒项目的持续发展，以加强我们的临床工作。在穆利根博士的项目中，将探索骨髓干细胞取代患病肌肉细胞的能力，而索德罗斯基博士的项目将研究艾滋病毒的适应性，使病毒能够进入人类细胞。这一提议的优势在于它专注于临床实验，同时收集基本重要的数据并探索新的领域。

The overall goal of this SCOR proposal is to develop and conduct clinical trials to correct congenital diseases of the human hematopoietic stem cell. The central theme of the research plan is the development of new methods of cellular and transduction gene therapy for these diseases. Specifically, we will develop new methods for stem cell transplantation across HLA barriers and will attempt to treat Fanconi Anemia and Diamond-Blackfan Anemia by replacement gene therapy protocols for these diseases. Dr. Guinan's project will focus on new advances in the biological and clinical aspects of haplomismatch bone marrow transplantation. Several projects will focus on the basic biology of Fanconi Anemia and Diamond- Blackfan Anemia and on Retroviral Transfection Scale-Up and Phase I gene therapy protocols for bone marrow transplantation. Other projects will focus on the continued development of retroviral and lentiviral programs which fortify our clinical efforts. In Dr. Mulligan's project, the capacity of bone marrow stem cells to replace diseased muscle cells will be explored while Dr. Sodroski's project will investigate the adaptations of HIV that will permit the virus access to human cells. The strength of this proposal lies in its focused drive toward clinical experimentation while gathering data of basic importance and exploring new frontiers.