Engineered U7 snRNA restores correct β-globin pre-mRNA splicing in mouse βIVS2-654- thalassemic erythroid progenitor cells.

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 snRNA that carried a sequence targeted to the cryptic branch point and an exonic splicing enhancer, U7.BP+623 snRNA. Here, 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.