Clinical trial of self-inactivating vectors for gene therapy of X-linked Severe Combined Immunodeficiency (SCID-X1)

基因疗法有可能治疗多种遗传性疾病。最近，一些试验表明，免疫系统有缺陷的儿童（通常被称为泡沫婴儿，因为他们被关在无菌室）可以通过将新基因注入称为骨髓的造血工厂而成功治疗。然而，使用改良的病毒或载体将新基因移植到骨髓中的方法，在少数儿童身上也显示出不幸的副作用。我们现在知道，这些产生是因为载体不可避免地激活了其他基因，这些基因使我们体内的细胞保持健康。在最坏的情况下，这可能导致癌症。然而，我们现在也相信，通过改进载体本身的设计，这种情况发生的风险可以得到很大的限制。在实验室进行了非常令人鼓舞的实验之后，我们现在想在常规骨髓移植困难的患者中测试这种策略。这不仅为免疫缺陷患者提供了一种新的治疗方法，而且为许多其他疾病的基因治疗提供了一个安全的平台。

Gene therapy has the potential to treat a wide range of inherited diseases. Recently, several trials have shown that children with defects of their immune system (often called bubble babies because they are kept in germ free rooms) can be successfully treated in this way by putting new genes into the blood-making factory called bone marrow. However, the way in which the new genes are transplanted into the bone marrow, using modified viruses or vectors, has also been shown in a few children to have unfortunate side-effects. We now know that these arise because the vectors inadvertantly activate other genes that keep the cells in our body healthy. In the worst case, this can cause cancer. However, we also now believe that the risk of this occuring can be substantially limited by improved design of the vectors themselves. Following on from highly encouraging experiments in the laboratory, we would now like to test this strategy in patients for whom coventional bone marrow transplantation is difficult. This will not only provide a new treatment for patients with immune defects, but will provide a platform on which gene therapy can be safely developed for many other diseases.