Enhancement of β-globin gene expression in thalassemic IVS2-654 induced pluripotent stem cell-derived erythroid cells by modified U7 snRNA

Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng

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5 Citations (Scopus)


The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of b-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat b-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 b-thalassemia. In this case, the aberration results from a mutation in the human b-globin intron 2 causing an aberrant splicing of b-globin pre-mRNA and preventing synthesis of functional b-globin protein. The iPSCs (derived from mesenchymal stromal cells from a patient with IVS2-654 b-thalassemia/hemoglobin (Hb) E) were transduced with a lentivirus carrying a modified U7 snRNA targeting an IVS2-654 b-globin pre-mRNA in order to restore the correct splicing. Erythroblasts differentiated from the transduced iPSCs expressed high level of correctly spliced b-globin mRNA suggesting that the modified U7 snRNA was expressed and mediated splicing correction of IVS2-654 b-globin pre-mRNA in these cells. Moreover, a less active apoptosis cascade process was observed in the corrected cells at transcription level. This study demonstrated the potential use of a genetically modified U7 snRNA with patient-specific iPSCs for the partial restoration of the aberrant splicing process of b-thalassemia.

Original languageEnglish
Pages (from-to)1059-1069
Number of pages11
JournalStem Cells Translational Medicine
Issue number4
Publication statusPublished - Apr 2017



  • B-Thalassemia
  • Induced pluripotent stem cell
  • Induced pluripotent stem cell-derived erythroblast
  • U7 snRNA

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Phanthong, P., Borwornpinyo, S., Kitiyanant, N., Jearawiriyapaisarn, N., Nuntakarn, L., Saetan, J., Nualkaew, T., Sa-Ngiamsuntorn, K., Anurathapan, U., Dinnyes, A., Kitiyanant, Y., & Hongeng, S. (2017). Enhancement of β-globin gene expression in thalassemic IVS2-654 induced pluripotent stem cell-derived erythroid cells by modified U7 snRNA. Stem Cells Translational Medicine, 6(4), 1059-1069. https://doi.org/10.1002/sctm.16-0121