Autor: |
Ekati Drakopoulou, Maria Georgomanoli, Carsten W. Lederer, Fottes Panetsos, Marina Kleanthous, Ersi Voskaridou, Dimitrios Valakos, Eleni Papanikolaou, Nicholas P. Anagnou |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
|
Zdroj: |
Viruses, Vol 14, Iss 12, p 2716 (2022) |
Druh dokumentu: |
article |
ISSN: |
1999-4915 |
DOI: |
10.3390/v14122716 |
Popis: |
We have previously demonstrated that both the original γ-globin lentiviral vector (LV) GGHI and the optimized GGHI-mB-3D LV, carrying the novel regulatory elements of the 3D HPFH-1 enhancer and the 3’ β-globin UTR, can significantly increase HbF production in thalassemic CD34+ cells and ameliorate the disease phenotype in vitro. In the present study, we investigated whether the GGHI-mB-3D vector can also exhibit an equally therapeutic effect, following the transduction of sickle cell disease (SCD) CD34+ cells at MOI 100, leading to HbF increase coupled with HbS decrease, and thus, to phenotype improvement in vitro. We show that GGHI-mB-3D LV can lead to high and potentially therapeutic HbF levels, reaching a mean 2-fold increase to a mean value of VCN/cell of 1.0 and a mean transduction efficiency of 55%. Furthermore, this increase was accompanied by a significant 1.6-fold HbS decrease, a beneficial therapeutic feature for SCD. In summary, our data demonstrate the efficacy of the optimized γ-globin lentiviral vector to improve the SCD phenotype in vitro, and highlights its potential use in future clinical SCD trials. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|