Laboratory of Cell and Gene Therapy, Biomedical Research Foundation of the Academy of Athens, Athens 115 27, Greece.
Curr Mol Med. 2013 Sep;13(8):1314-30. doi: 10.2174/15665240113139990064.
β-thalassemias constitute hereditary blood disorders characterized by reduced or absence of β-globin synthesis resulting in mild to severe anemia, depending on the genotype. More than 200 mutations in the β-globin gene are responsible for their specific features leading to a very heterogeneous phenotype. Current therapies for β-thalassemia include blood transfusions, usually along with iron chelation and in selected cases with bone marrow transplantation (BMT) of HLA-matched hematopoietic stem cells (HSCs). However, these approaches are limited by factors, such as iron overload and donor availability, respectively. Since 2000, when globin lentiviral vectors (LVs) were first successfully tested for transfer efficiency of the therapeutic transgene, which led to disease amelioration in murine models, attention was drawn towards the improvement of such vectors for β-thalassemia gene therapy. Constantly improving vector design and efficient HSC manipulation led recently to the first successful clinical trial in France, which further proved that this genetic approach can be curative. Furthermore, improved new efficient vectors and methods to safely monitor integration sites and therapeutic transgene position effects, promise a new era for β-thalassemia gene therapy, with more and safer clinical trials yet to come.
β-地中海贫血症是一种遗传性血液疾病，其特征是β-球蛋白的合成减少或缺失，导致轻度至重度贫血，具体取决于基因型。超过 200 种β-珠蛋白基因突变导致其具有非常异质性的表型。β-地中海贫血症的当前治疗方法包括输血，通常与铁螯合治疗一起使用，在某些情况下还使用与 HLA 匹配的造血干细胞（HSCs）进行骨髓移植（BMT）。然而，这些方法受到铁过载和供体可用性等因素的限制。自 2000 年首次成功测试用于治疗转基因的基因传递效率的珠蛋白慢病毒载体（LV）以来，这些方法导致了小鼠模型中疾病的改善，人们开始关注此类载体在β-地中海贫血症基因治疗中的改进。不断改进的载体设计和有效的 HSC 操作最近导致了法国的首次成功临床试验，进一步证明了这种遗传方法可以治愈疾病。此外，改进的新型高效载体和方法可安全监测整合位点和治疗性转基因的位置效应，为β-地中海贫血症基因治疗带来了一个新时代，未来还将有更多、更安全的临床试验。
