| Amelioration of β^654-thalassemia in mouse model with the knockdown of aberrantly spliced β-globin mRNA |
| |
| 作者单位： | Shanghai Institute of Medical Genetics, Shanghai Children＇s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China. |
| |
| 基金项目： | 国家重点基础研究发展计划(973计划)，国家高技术研究发展计划(863计划)，国家自然科学基金，上海市重点学科建设项目 |
| |
| 摘 要： | Large amounts of aberrantly spliced mRNA from the β654 allele was present in erythroid cells, which might impair the erythropoiesis.A therapeutic strategy for β-thalassemia was explored by knocking down the aberrantly spliced mRNA of β-globin. Lentiviral vector with siRNA fragment targets on the specific portion of β654-globin aberrantly spliced pre-mRNA was constructed. In HeLa β654 cells, the siRNA vector could reduce approximately 60% of aberrantly spliced mRNA, which was assessed by RT-PCR and qRT-PCR. Furthermore, a disease model of β654 thalassemia mice with lentiviral-mediated siRNA was produced by subzonal injection (named Hβi-Hbbth-4/Hbb+transgenic mice). Our results showed that the hemotological parameters were improved in Hβi-Hbbth-4/Hbb+ transgenic mice. This study provides a potential way for β654-thalassemia therapy by knocking down the aberrantly spliced β-globin mRNA, whilst supporting that the aberrantly spliced β-globin mRNA may aggravate the disease.
|
| 关 键 词： | RNA 核糖核酸 球蛋白 细胞 生物研究 |
Amelioration of β654-thalassemia in mouse model with the knockdown of aberrantly spliced β-globin mRNA |
| |
| Authors: | Shuyang Xie Wei Li Zhaorui Ren Jingzhi Zhang Xinbin Guo Shu Wang Shuzhen Huang Fanyi Zeng Yi-Tao Zeng |
| |
| Abstract: | Large amounts of aberrantly spliced mRNA from the β654 allele was present in erythroid cells, which might impair the erythropoiesis.A therapeutic strategy for β-thalassemia was explored by knocking down the aberrantly spliced mRNA of β-globin. Lentiviral vector with siRNA fragment targets on the specific portion of β654-globin aberrantly spliced pre-mRNA was constructed. In HeLa β654 cells, the siRNA vector could reduce approximately 60% of aberrantly spliced mRNA, which was assessed by RT-PCR and qRT-PCR. Furthermore, a disease model of β654 thalassemia mice with lentiviral-mediated siRNA was produced by subzonal injection (named Hβi-Hbbth-4/Hbb+transgenic mice). Our results showed that the hemotological parameters were improved in Hβi-Hbbth-4/Hbb+ transgenic mice. This study provides a potential way for β654-thalassemia therapy by knocking down the aberrantly spliced β-globin mRNA, whilst supporting that the aberrantly spliced β-globin mRNA may aggravate the disease. |
| |
| Keywords: | small interfering RNA (siRNA) hemoglobin |
| 本文献已被 维普 万方数据 等数据库收录！ |
