Bank Arthur, Dorazio Ronald, Leboulch Philippe
Genetix Pharmaceuticals, Cambridge, Massachusetts 02139, USA.
Ann N Y Acad Sci. 2005;1054:308-16. doi: 10.1196/annals.1345.007.
Recent success in the long-term correction of mouse models of human beta-thalassemia and sickle cell anemia by lentiviral vectors and evidence of high gene transfer and expression in transduced human hematopoietic cells have led to a first clinical trial of gene therapy for the disease. A LentiGlobin vector containing a beta-globin gene (beta(A-T87Q)) that produces a hemoglobin (Hbbeta(A-T87Q)) that can be distinguished from normal hemoglobin will be used. The LentiGlobin vector is self-inactivating and contains large elements of the beta-globin locus control region as well as chromatin insulators and other features that should prevent untoward events. The study will be done in Paris with Eliane Gluckman as the principal investigator and Philippe Leboulch as scientific director.
近期,慢病毒载体在长期纠正人类β地中海贫血和镰状细胞贫血小鼠模型方面取得成功,并且有证据表明转导的人类造血细胞中基因转移和表达水平较高,这促成了针对该疾病的首次基因治疗临床试验。将使用一种携带β珠蛋白基因(β(A-T87Q))的慢病毒载体LentiGlobin,该基因产生的血红蛋白(Hbbeta(A-T87Q))可与正常血红蛋白区分开来。LentiGlobin载体是自我失活的,包含β珠蛋白基因座控制区的大片段以及染色质绝缘子和其他可防止不良事件发生的特征。该研究将在巴黎进行,以伊莲娜·格鲁克曼为主要研究者,菲利普·勒布尔什为科学主任。