Engineered U7 Small Nuclear RNA Restores Correct ß-Globin Pre-mRNA Splicing in Mouse ßIVS2-654-Thalassemic Erythroid Progenitor Cells.
Hum Gene Ther
; 32(9-10): 473-480, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-32977730
ABSTRACT
Restoration of correct splicing of ßIVS2-654-globin pre-mRNA was previously accomplished in erythroid cells from ß-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 ßIVS2-654 mutation. While correction of ßIVS2-654 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Precursores de RNA
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Globinas beta
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article