Hoogerbrugge P M, von Beusechem V W, Kaptein L C, Einerhand M P, Valerio D
Department of Medical Biochemistry, IntroGene B.V., Rijswijk, The Netherlands.
Br Med Bull. 1995 Jan;51(1):72-81. doi: 10.1093/oxfordjournals.bmb.a072954.
In the last decade, gene transfer into hematopoietic cells has evolved from an experimental procedure which resulted in successfully transduced in vitro hematopoietic colonies to the first clinical trials in patients suffering from severe combined immunodeficiency disease caused by the absence of functional adenosine deaminase. Significant in vivo expression of the newly introduced gene encoding human adenosine deaminase has been observed in descendents of murine and rhesus monkey hematopoietic stem cells following retrovirus mediated gene transfer. So far, 10 patients have received genetically repaired T-cells, hematopoietic stem cells or both without the appearance of any side effect. The clinical bone marrow gene transfer studies differ largely from the monkey studies with respect to myeloablation, which was applied in the monkey studies, but not in the patient studies. Ongoing studies in patients show that the introduced gene is present in circulating blood cells. In the initial phase of the trial, the frequency of transduced circulating blood cells is lower than in rhesus monkey studies. This difference may be contributed to the fact that conditioning was not performed in the patients.
在过去十年中，将基因导入造血细胞已从一种能在体外成功转导造血集落的实验方法，发展到应用于患有因缺乏功能性腺苷脱氨酶导致的重症联合免疫缺陷病患者的首次临床试验。在逆转录病毒介导的基因转移后，在小鼠和恒河猴造血干细胞的后代中观察到了新引入的编码人腺苷脱氨酶基因的显著体内表达。到目前为止，已有10名患者接受了基因修复的T细胞、造血干细胞或两者，且未出现任何副作用。临床骨髓基因转移研究在骨髓消融方面与猴子研究有很大不同，骨髓消融应用于猴子研究，但未应用于患者研究。正在进行的患者研究表明，导入的基因存在于循环血细胞中。在试验的初始阶段，转导的循环血细胞频率低于恒河猴研究中的频率。这种差异可能是由于患者未进行预处理。
