Amelioration of β654-thalassemia in mouse model with the knockdown of aberrantly spliced β-globin mRNA

Shuyang Xie; Wei Li; Zhaorui Ren; Jingzhi Zhang; Xinbin Guo; Shu Wang; Shuzhen Huang; Fanyi Zeng; Yi-Tao Zeng

doi:10.1016/S1673-8527(08)60080-6

Volume 35 Issue 10

Oct. 2008

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Article Navigation > Journal of Genetics and Genomics > 2008 > 35(10): 595-601

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Amelioration of β654-thalassemia in mouse model with the knockdown of aberrantly spliced β-globin mRNA

doi: 10.1016/S1673-8527(08)60080-6

Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China

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Corresponding author: E-mail address: zengfy@shsmu.edu.cn (Fanyi Zeng); E-mail address: ytzeng@stn.sh.cn (Yi-Tao Zeng)
Received Date: 2008-03-04
Accepted Date: 2008-09-02
Rev Recd Date: 2008-08-31

Available Online: 2008-10-18

Publish Date: 2008-10-20

Abstract

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-Hbb^th-4/Hbb⁺ transgenic mice). Our results showed that the hemotological parameters were improved in Hβi-Hbb^th-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.
- β-thalassemia,
- small interfering RNA (siRNA),
- hemoglobin

These authors contributed equally to this work.

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References(17)

References

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