Ribozyme-mediated repair of sickle β-globin mRNAs in erythrocyte precursors
Ribozyme-mediated repair of sickle β-globin mRNAs in erythrocyte precursors
复制标题
DOI：
10.1126/science.280.5369.1593
复制
发表时间：
1998-06-05
期刊：
影响因子：
56.9
通讯作者：
Sullenger, BA
中科院分区：
文献类型：
--
作者：
Lan, N;Howrey, RP;Sullenger, BA
镰状细胞性贫血是最常见的遗传性血液病，但没有治愈性治疗存在这种疾病。此外，珠蛋白基因表达的复杂性使得基于基因疗法的血红蛋白病治疗的开发变得困难。镰状细胞疗法的另一种遗传方法是基于RNA修复。使用反式剪接I组核酶来改变镰状细胞病个体外周血中红细胞前体中的突变β-珠蛋白转录物。镰状β-珠蛋白转录物被转化为编码抗镰状蛋白γ-珠蛋白的信使RNA。这些结果表明，RNA修复可能成为治疗遗传疾病的一种有用的方法。
Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene therapy difficult. An alternative genetic approach to sickle cell therapy is based on RNA repair. A trans-splicing group I ribozyme was used to alter mutant beta-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Sickle beta-globin transcripts were converted into messenger RNAs encoding the anti-sickling protein gamma-globin. These results suggest that RNA repair may become a useful approach in the treatment of genetic disorders.