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

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)

These authors contributed equally to this work.

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

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

Corresponding author: E-mail address: zengfy@shsmu.edu.cn (Fanyi Zeng); E-mail address: ytzeng@stn.sh.cn (Yi-Tao Zeng)

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

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

Corresponding author: E-mail address: zengfy@shsmu.edu.cn (Fanyi Zeng); E-mail address: ytzeng@stn.sh.cn (Yi-Tao Zeng)

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