Williams D A, Smith F O
Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Hum Gene Ther. 2000 Oct 10;11(15):2059-66. doi: 10.1089/104303400750001372.
A report by French physician-scientists suggests a successful application of gene transfer methods in the treatment of two children with severe combined immunodeficiency (SCID) due to defective interleukin 2 receptor common gamma chain. The protocol used in this clinical trial was derived from a number of preclinical and basic studies leading to improved transduction of hematopoietic stem and primitive progenitor cells using retrovirus vectors. These improvements have also been shown to impact transduction of a long-lived progenitor cell in a chemotherapy protocol in cancer patients. The improved results of these human trials come during a period of increased scrutiny and criticism of human gene therapy trials, due, in part, to significant toxicities in some trials using adenovirus-based vectors. The potential efficacy versus toxicity of phase I trials of human gene therapy is also under question. After many years of research, however, there appears to be real evidence that genetic diseases may be successfully treated by gene transfer techniques. Future clinical studies should be based on continued progress in the understanding of the toxicology of gene delivery systems, vector technology, and target cell manipulation.
法国医生科学家的一份报告表明，基因转移方法成功应用于治疗两名因白细胞介素2受体共同γ链缺陷而患有重症联合免疫缺陷（SCID）的儿童。该临床试验中使用的方案源自多项临床前和基础研究，这些研究使得利用逆转录病毒载体对造血干细胞和原始祖细胞的转导得到了改善。这些改进也已显示出会影响癌症患者化疗方案中长寿祖细胞的转导。这些人体试验取得的改进结果是在对人类基因治疗试验的审查和批评增多的时期出现的，部分原因是一些使用腺病毒载体的试验出现了显著毒性。人类基因治疗I期试验的潜在疗效与毒性也受到质疑。然而，经过多年研究，似乎有确凿证据表明基因转移技术可能成功治疗遗传疾病。未来的临床研究应基于在基因传递系统毒理学、载体技术和靶细胞操作理解方面的持续进展。
