Publication: Engineered U7 Small Nuclear RNA Restores Correct β-Globin Pre-mRNA Splicing in Mouse β<sup>iVS2-654</sup>-Thalassemic Erythroid Progenitor Cells
Issued Date
2021-05-01
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ISSN
15577422
10430342
10430342
Other identifier(s)
2-s2.0-85101504394
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Mahidol University
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SCOPUS
Bibliographic Citation
Human Gene Therapy. Vol.32, No.9-10 (2021), 473-480
Suggested Citation
Annette D'Arqom, Tiwaporn Nualkaew, Natee Jearawiriyapaisarn, Ryszard Kole, Saovaros Svasti Engineered U7 Small Nuclear RNA Restores Correct β-Globin Pre-mRNA Splicing in Mouse β<sup>iVS2-654</sup>-Thalassemic Erythroid Progenitor Cells. Human Gene Therapy. Vol.32, No.9-10 (2021), 473-480. doi:10.1089/hum.2020.145 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76199
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Title
Engineered U7 Small Nuclear RNA Restores Correct β-Globin Pre-mRNA Splicing in Mouse β<sup>iVS2-654</sup>-Thalassemic Erythroid Progenitor Cells
Abstract
Restoration of correct splicing of βIVS2-654-globin pre-mRNA was previously accomplished in erythroid cells from β-thalassemia/HbE patients by an engineered U7 small nuclear RNA (snRNA) that carried a sequence targeted to the cryptic branch point and an exonic splicing enhancer, U7.BP+623 snRNA. In this study, this approach was tested in thalassemic mice carrying the βIVS2-654 mutation. While correction of βIVS2-654 pre-mRNA splicing was achieved in erythroid progenitors transduced with a lentiviral vector carrying the U7.BP+623 snRNA, a high level of truncated U7.BP+623 snRNA was also observed. The discrepancy of processing of the modified U7 snRNA in human and mouse constructs hamper the evaluation of pathologic improvement in mouse model.