Zentilin L, Tafuro S, Serra C, Falaschi A, Giacca M
Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Ann Ist Super Sanita. 1998;34(4):447-55.
Chronic granulomatous disease (CGD) is an inherited immunodeficiency characterized by severe recurrent bacterial and fungal infections of several organs. The disease is due to the inability of phagocytic leukocytes to generate reactive oxygen species upon phagocytosis. The defect arises as a consequence of mutations of the genes encoding for the subunits of a membrane NADPH oxidase, which catalyzes the production of superoxide anion (O2-). CGD represents an ideal candidate disorder for gene therapy, since the disease has a recessive inheritance, its phenotype is exclusively expressed in phagocytic cells, and a partial correction is likely to be effective. Given the short half-life of mature phagocytes, the optimal target cell population for gene transfer is the pluripotent hematopoietic stem cell. Transduction of CD34+ hematopoietic progenitors with retroviral vectors carrying the cDNA of the defective gene results in the correction of the enzymatic defect in myeloid cells differentiated in vitro. Still, the effective development of a clinical gene therapy protocol for this disease will await a substantial improvement in our current technology for the identification and manipulation of hematopoietic stem cells, and in our understanding of their biological and molecular properties.
慢性肉芽肿病（CGD）是一种遗传性免疫缺陷病，其特征为多个器官出现严重的反复细菌和真菌感染。该疾病是由于吞噬性白细胞在吞噬作用时无法产生活性氧物质所致。这种缺陷是由编码膜NADPH氧化酶亚基的基因突变引起的，该酶催化超氧阴离子（O2-）的产生。CGD是基因治疗的理想候选疾病，因为该疾病为隐性遗传，其表型仅在吞噬细胞中表达，而且部分纠正可能有效。鉴于成熟吞噬细胞的半衰期较短，基因转移的最佳靶细胞群体是多能造血干细胞。用携带缺陷基因cDNA的逆转录病毒载体转导CD34+造血祖细胞，可纠正体外分化的髓细胞中的酶缺陷。尽管如此，针对该疾病的临床基因治疗方案的有效开发仍有待我们目前用于鉴定和操纵造血干细胞的技术以及我们对其生物学和分子特性的理解有实质性的改进。
