| Autor: |
Drakopoulou E; Laboratory of Cell and Gene Therapy, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 11527 Athens, Greece.; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece., Georgomanoli M; Laboratory of Cell and Gene Therapy, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 11527 Athens, Greece.; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece., Lederer CW; The Molecular Genetics Thalassemia Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus., Panetsos F; Bioiatriki SA Health Group Company, 11526 Athens, Greece., Kleanthous M; The Molecular Genetics Thalassemia Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus., Voskaridou E; Thalassemia and Sickle Cell Disease Centre, Laiko General Hospital, 11527 Athens, Greece., Valakos D; Laboratory of Molecular Biology, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 11527 Athens, Greece., Papanikolaou E; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece., Anagnou NP; Laboratory of Cell and Gene Therapy, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 11527 Athens, Greece.; Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece. |
| Abstrakt: |
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. |
