Publication: Repair of a splicing defect in erythroid cells from patients with β-thalassemia/HbE disorder
Issued Date
2002-12-01
Resource Type
ISSN
15250016
Other identifier(s)
2-s2.0-0036942827
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Therapy. Vol.6, No.6 (2002), 718-726
Suggested Citation
Thipparat Suwanmanee, Halina Sierakowska, Suthat Fucharoen, Ryszard Kole Repair of a splicing defect in erythroid cells from patients with β-thalassemia/HbE disorder. Molecular Therapy. Vol.6, No.6 (2002), 718-726. doi:10.1006/mthe.2002.0805 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/20024
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Title
Repair of a splicing defect in erythroid cells from patients with β-thalassemia/HbE disorder
Abstract
A HeLa cell line stably expressing the human β-globin gene carrying thalassemic mutations βE/IVS1-6 served as a thalassemia model for repair of aberrant splicing of ΒE/IVS1-globin pre-mRNA with antisense oligonucleotides. Treatment of βE/IVS1-6 HeLa cells with a morpholino oligonucleotide targeted immediately upstream of the aberrant 5′ splice site activated by the mutations resulted in an increase in the amount of correctly spliced βE-globin mRNA in a dose-dependent and sequence-specific fashion. The repaired βE-globin mRNA was stable and could be translated into full-length βE-globin polypeptide. Application of the same oligonucleotide to erythroid progenitor cells from two β-thalassemia/HbE patients resulted in an approximately 70% increase in correct βE-globin mRNA and 36% increase in hemoglobin E. The erythroid progenitor cells represent the actual targets for the clinical application of antisense repair of defective pre-mRNAs.