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
de En
| MEDLINE
| ID: mdl-32977730
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Précurseurs des ARN
/
Globines bêta
Limites:
Animals
/
Humans
Langue:
En
Journal:
Hum Gene Ther
Sujet du journal:
GENETICA MEDICA
/
TERAPEUTICA
Année:
2021
Type de document:
Article
Pays de publication:
États-Unis d'Amérique