Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the β A(T87Q) - Globin Gene

作者：Olivier Nègre, Anne-Virginie Eggimann, Yves Beuzard, Jean‐Antoine Ribeil, Philippe Bourget, Suparerk Borwornpinyo, Suradej Hongeng, Salima Hacein‐Bey, Marina Cavazzana, Philippe Leboulch, Emmanuel Payen · 发表于：Human Gene Therapy · 年份：2016 · DOI：10.1089/hum.2016.007 · 被引用次数：159 · 研究领域：Hemoglobinopathies and Related Disorders、Prenatal Screening and Diagnostics、Iron Metabolism and Disorders

β-globin gene disorders are the most prevalent inherited diseases worldwide and result from abnormal β-globin synthesis or structure. Novel therapeutic approaches are being developed in an effort to move beyond palliative management. Gene therapy, by ex vivo lentiviral transfer of a therapeutic β-globin gene derivative (β(AT87Q)-globin) to hematopoietic stem cells, driven by cis-regulatory elements that confer high, erythroid-specific expression, has been evaluated in human clinical trials over the past 8 years. β(AT87Q)-globin is used both as a strong inhibitor of HbS polymerization and as a biomarker. While long-term studies are underway in multiple centers in Europe and in the United States, proof-of-principle of efficacy and safety has already been obtained in multiple patients with β-thalassemia and sickle cell disease.