Browsing by Author "Graduate Program in Molecular Medicine"

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    Engineered U7 Small Nuclear RNA Restores Correct β-Globin Pre-mRNA Splicing in Mouse βiVS2-654-Thalassemic Erythroid Progenitor Cells
    (2021-05-01) Annette D'Arqom; Tiwaporn Nualkaew; Natee Jearawiriyapaisarn; Ryszard Kole; Saovaros Svasti; Universitas Airlangga; The University of North Carolina at Chapel Hill; Mahidol University; Institute of Molecular Biosciences, Mahidol University; Graduate Program in Molecular Medicine
    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.