A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34+ cells from the bone marrow of human immunodeficiency virus-1-infected children
A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34+ cells from the bone marrow of human immunodeficiency virus-1-infected children
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DOI：
10.1182/blood.v94.1.368.413a47_368_371
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发表时间：
1999-07-01
期刊：
影响因子：
20.3
通讯作者：
Church, J
中科院分区：
文献类型：
--
作者：
Kohn, DB;Bauer, G;Church, J
用抑制人类免疫缺陷病毒-1（HIV-1）复制的基因对造血干细胞进行遗传修饰，可导致移植后产生抗HIV-1感染的T淋巴细胞和单核细胞。我们进行了一项临床试验，以评估该程序的安全性和可行性，使用4名HIV-1感染的儿科受试者（年龄8至17岁）的骨髓。我们获得骨髓，分离CD 34（+）细胞，用携带Rev反应元件（RRE）诱饵基因的逆转录病毒载体进行体外转导，并将细胞重新输注到这些受试者体内，没有任何不良反应的证据。基因转移/细胞输注后1年内外周血样本中含基因白细胞的水平极低。这些观察结果支持使用造血细胞进行HIV-1基因治疗的潜力，但强调需要改进基因转移技术。(C)1999年，美国血液学会。
Genetic modification of hematopoietic stem cells with genes that inhibit replication of human immunodeficiency virus-1 (HIV-1) could lead to development of T lymphocytes and monocytic cells resistant to HIV-1 infection after transplantation. We performed a clinical trial to evaluate the safety and feasibility of this procedure, using bone marrow from four HIV-1-infected pediatric subjects (ages 8 to 17 years). We obtained bone marrow, isolated CD34(+) cells, performed in vitro transduction with a retroviral vector carrying a rev-responsive element (RRE) decoy gene, and reinfused the cells into these subjects with no evidence of adverse effects. The levels of gene-containing leukocytes in peripheral blood samples in the 1 year after gene transfer/cell infusion have been extremely low. These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques. (C) 1999 by The American Society of Hematology.