首页> 外文期刊>Nature >Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin
【24h】

Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin

机译:表达慢病毒编码人β-珠蛋白的β地中海贫血小鼠的治疗性血红蛋白合成

获取原文
获取原文并翻译 | 示例
           

摘要

The stable introduction of a functional β-globin gene in haematopoietic stem cells could be a powerful approach to treat β-thalassaemia and sickle-cell disease. Genetic approaches aiming to increase normal β-globin expression in the progeny of auto-logous haematopoietic stem cells might circumvent the limitations and risks of allogeneic cell transplants. However, low-level expression, position effects and transcriptional silencing hampered the effectiveness of viral transduction of the human β-globin gene when it was linked to minimal regulatory sequences. Here we show that the use of recombinant lentiviruses enables efficient transfer and faithful integration of the human β-globin gene together with large segments of its locus control region. In long-term recipients of unselected transduced bone marrow cells, tetramers of two murine α-globin and two human β~A-globin molecules account for up to 13% of total haemoglobin in mature red cells of normal mice. In β-thalassaemic heterozygous mice higher percentages are obtained (17% to 24%), which are sufficient to ameliorate anaemia and red cell morphology. Such levels should be of therapeutic benefit in patients with severe defects in haemoglobin production.
机译:在造血干细胞中稳定引入功能性β-珠蛋白基因可能是治疗β地中海贫血和镰状细胞疾病的有效方法。旨在增加自体造血干细胞后代中正常β-珠蛋白表达的遗传方法可能会规避同种异体细胞移植的局限性和风险。然而,低水平的表达,位置效应和转录沉默阻碍了人β-珠蛋白基因与最小调控序列连接时病毒转导的有效性。在这里,我们显示重组慢病毒的使用可以使人β-珠蛋白基因及其基因座控制区的较大片段有效转移并忠实整合。在未选择的转导骨髓细胞的长期接受者中,正常鼠成熟的红细胞中,两个鼠类α-球蛋白和两个人β-A-球蛋白分子的四聚体最多占总血红蛋白的13%。在β-地中海贫血杂合小鼠中,可获得更高的百分比(17%至24%),足以缓解贫血和红细胞形态。这样的水平对血红蛋白产生严重缺陷的患者应具有治疗益处。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号