STEM CELL THERAPY OF CONGENITAL DEFECTS IN HEMATOPOIESIS

该SCOR提案的总体目标是开发并开展临床试验，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为这些疾病开发细胞和转导基因治疗的新方法。具体来说，我们将开发跨越HLA屏障的干细胞移植新方法，并尝试通过替代基因治疗方案治疗Fanconi贫血和Diamond-Blackfan贫血。Guinan博士的项目将重点关注haplomismatch骨髓移植在生物学和临床方面的新进展。几个项目将侧重于范可尼贫血和钻石-布莱克凡贫血的基础生物学，以及骨髓移植的逆转录病毒转染放大和I期基因治疗方案。其他项目将集中于继续发展逆转录病毒和慢病毒方案，以加强我们的临床工作。在Mulligan博士的项目中，将探索骨髓干细胞替代患病肌肉细胞的能力，而Sodroski博士的项目将研究HIV的适应性，使病毒能够进入人体细胞。这一建议的优势在于它在收集基本重要数据和探索新领域的同时，重点推动临床实验。

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.