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

基因疗法具有治疗多种遗传性疾病的潜力。最近，几项试验表明，通过将新基因植入造血工厂骨髓，免疫系统有缺陷的儿童（通常被称为泡泡婴儿，因为他们被放在无菌的房间里）可以成功地得到治疗。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，在一些儿童身上也显示出令人遗憾的副作用。我们现在知道，这是因为载体无意中激活了保持我们体内细胞健康的其他基因。在最坏的情况下，这会导致癌症。然而，我们现在也相信，通过改进载体本身的设计，可以大大限制发生这种情况的风险。在实验室进行了高度鼓舞人心的实验之后，我们现在想在传统骨髓移植难以进行的患者身上测试这一策略。这不仅将为免疫缺陷患者提供一种新的治疗方法，而且将提供一个平台，在这个平台上，基因治疗可以安全地开发用于许多其他疾病。

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.