Persons Derek A, Nienhuis Arthur W
St. Jude Children's Research Hospital, 332 North Lauderdale Drive, Memphis, TN 38105, USA.
Curr Hematol Rep. 2003 Jul;2(4):348-55.
The hematologic disorders of beta-thalassemia and sickle cell disease are the most prevalent of human genetic diseases. Although palliative therapies and curative stem cell transplantation therapy have been developed for these disorders, treatment still remains suboptimal and many patients suffer significant morbidity and early mortality. Therefore, development of a gene therapy approach has been sought for many years. Major progress in the globin gene therapy field has been achieved by several laboratories. Using lentiviral vectors to obtain high-level expression of complex globin gene cassettes, therapeutic correction of several murine models of beta-thalassemia, and sickle cell disease was recently reported. This progress, coupled with developments in the ability to select and expand genetically modified stem cells in vivo, has advanced the possibility of gene therapy for the hemoglobin disorders in the near future. We review the developments in several areas that are critical for successful gene therapy of the hemoglobin disorders.
β地中海贫血和镰状细胞病的血液系统疾病是人类最常见的遗传疾病。尽管已经针对这些疾病开发了姑息疗法和治愈性干细胞移植疗法，但治疗效果仍不理想，许多患者遭受严重的发病和早期死亡。因此，多年来一直在寻求基因治疗方法。多个实验室在珠蛋白基因治疗领域取得了重大进展。最近有报道称，使用慢病毒载体获得复杂珠蛋白基因盒的高水平表达，对几种β地中海贫血和镰状细胞病的小鼠模型进行了治疗性纠正。这一进展，再加上体内选择和扩增基因修饰干细胞能力的发展，提高了在不久的将来对血红蛋白疾病进行基因治疗的可能性。我们综述了对血红蛋白疾病成功进行基因治疗至关重要的几个领域的进展。
