CLINICAL TRIAL: TRANSDUCTION OF CD34+ CELLS FROM THE UMBILICAL CORD BLOOD OF INF

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项提议的中心假设是： 用逆转录病毒载体将正常的人ADA基因导入未接受聚乙二醇腺苷置换的ADA缺陷型SCID患儿的CD34造血干细胞是安全的，可产生成熟的T淋巴细胞，表达ADA酶活性，恢复免疫功能。 总之，这些临床研究将确定当前逆转录病毒介导的基因转移技术将基因从骨髓导入人类造血干细胞的安全性和有效性。将比较两种不同的逆转录病毒载体GCsap-M-ADA和MND-ADA表达人ADA基因的能力，并赋予T淋巴细胞选择性存活优势。在没有聚乙二醇ADA的情况下，将测试骨髓细胞减少，以评估该方法的安全性及其对基因校正细胞的植入和选择性存活的影响。此外，还将评估ADA缺乏的SCID患者重建免疫的具体益处。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The central hypothesis of this proposal is: Retroviral-mediated transfer of a normal human ADA cDNA into CD34+ hematopoietic stem cells of infants and children with ADA-deficient SCID, who have undergone marrow cytoreduction and are not on PEG-ADA replacement, can be performed safely and will result in the production of mature T lymphocytes, expressing ADA enzyme activity and restoring immune function. In all, these clinical studies will determine the safety and effectiveness of current retroviral-mediated gene transfer techniques to introduce genes into human hematopoietic stem cells from the bone marrow. Two different retroviral vectors, GCsap-M-ADA and MND-ADA, will be compared for their abilities to express the human ADA cDNA and confer a selective survival advantage upon T lymphocytes. Marrow cytoreduction in the absence of PEG-ADA will be tested, to assess the safety of the approach and its effect on engraftment and selective survival of gene-corrected cells. Additionally, the specific benefits for reconstitution of immunity in ADA-deficient SCID patients will be assessed.