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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这一建议的核心假设是： 逆转录病毒介导的正常人ADA cDNA转移到ADA缺陷型SCID婴儿和儿童的CD 34+造血干细胞中，这些婴儿和儿童接受了骨髓细胞减少术，未接受PEG-ADA替代，可以安全地进行，并将导致成熟T淋巴细胞的产生，表达ADA酶活性并恢复免疫功能。 总之，这些临床研究将确定目前逆转录病毒介导的基因转移技术的安全性和有效性，将基因从骨髓导入人类造血干细胞。 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 cDNA并赋予T淋巴细胞选择性存活优势的能力。 将在不存在PEG-ADA的情况下测试骨髓细胞减少，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缺陷型SCID患者免疫重建的具体获益。

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.