Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease
Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease
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DOI：
10.1073/pnas.94.22.12133
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发表时间：
1997-10-28
影响因子：
11.1
通讯作者：
Gallin, JI
中科院分区：
文献类型：
--
作者：
Malech, HL;Maples, PB;Gallin, JI
很少有人知道自体造血干细胞移植的潜力，在成人不受清髓性预处理方案。5名患有p47（phox）缺陷型慢性肉芽肿病的成年患者接受了自体CD 34（+）外周血干细胞（PBSC）的静脉输注，这些外周血干细胞已被编码正常p47（phox）的重组逆转录病毒体外转导。虽然没有给予骨髓预处理，但在所有5例患者的外周血中均可检测到功能校正的粒细胞。峰值校正发生在输注后3-6周，范围为总外周血粒细胞的0.004 - 0.05%。在一些个体中，在输注后长达6个月的时间内可检测到校正的细胞。因此，自体PBSC的长期植入和转导基因的持续表达可以在成人中发生而无需调节。该试验还试验了使用无动物蛋白培养基和与血库相容的透气塑料容器的封闭系统来培养和转导PBSC。这些特征增强了PBSC定向基因治疗的安全性。
Little is known about the potential for engraftment of autologous hematopoietic stem cells in human adults not subjected to myeloablative conditioning regimens. Five adult patients with the p47(phox) deficiency form of chronic granulomatous disease received intravenous infusions of autologous CD34(+) peripheral blood stem cells (PBSCs) that had been transduced ex vivo with a recombinant retrovirus encoding normal p47(phox). Although marrow conditioning was not given, functionally corrected granulocytes were detectable in peripheral blood of all five patients. Peak correction occurred 3-6 weeks after infusion and ranged from 0.004 to 0.05% of total peripheral blood granulocytes. Corrected cells were detectable for as long as 6 months after infusion in some individuals. Thus, prolonged engraftment of autologous PBSCs and continued expression of the transduced gene can occur in adults without conditioning. This trial also piloted the use of animal protein-free medium and a blood-bank-compatible closed system of gas-permeable plastic containers for culture and transduction of the PBSCs. These features enhance the safety of PBSCs directed gene therapy.