Academic Journal
Coordinated β-globin expression and α2-globin reduction in a multiplex lentiviral gene therapy vector for β-thalassemia.
| العنوان: | Coordinated β-globin expression and α2-globin reduction in a multiplex lentiviral gene therapy vector for β-thalassemia. |
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| المؤلفون: | Nualkaew, T, Sii-Felice, K, Giorgi, M, McColl, B, Gouzil, J, Glaser, A, Voon, HPJ, Tee, HY, Grigoriadis, G, Svasti, S, Fucharoen, S, Hongeng, S, Leboulch, P, Payen, E, Vadolas, J |
| بيانات النشر: | Elsevier BV |
| سنة النشر: | 2021 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | A primary challenge in lentiviral gene therapy of β-hemoglobinopathies is to maintain low vector copy numbers to avoid genotoxicity while being reliably therapeutic for all genotypes. We designed a high-titer lentiviral vector, LVβ-shα2, that allows coordinated expression of the therapeutic βA-T87Q-globin gene and of an intron-embedded miR-30-based short hairpin RNA (shRNA) selectively targeting the α2-globin mRNA. Our approach was guided by the knowledge that moderate reduction of α-globin chain synthesis ameliorates disease severity in β-thalassemia. We demonstrate that LVβ-shα2 reduces α2-globin mRNA expression in erythroid cells while keeping α1-globin mRNA levels unchanged and βA-T87Q-globin gene expression identical to the parent vector. Compared with the first βA-T87Q-globin lentiviral vector that has received conditional marketing authorization, BB305, LVβ-shα2 shows 1.7-fold greater potency to improve α/β ratios. It may thus result in greater therapeutic efficacy and reliability for the most severe types of β-thalassemia and provide an improved benefit/risk ratio regardless of the β-thalassemia genotype. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1525-0016 1525-0024 |
| Relation: | pii: S1525-0016(21)00251-3; Nualkaew, T., Sii-Felice, K., Giorgi, M., McColl, B., Gouzil, J., Glaser, A., Voon, H. P. J., Tee, H. Y., Grigoriadis, G., Svasti, S., Fucharoen, S., Hongeng, S., Leboulch, P., Payen, E. & Vadolas, J. (2021). Coordinated β-globin expression and α2-globin reduction in a multiplex lentiviral gene therapy vector for β-thalassemia. Mol Ther, 29 (9), pp.2841-2853. https://doi.org/10.1016/j.ymthe.2021.04.037.; http://hdl.handle.net/11343/301840 |
| الاتاحة: | http://hdl.handle.net/11343/301840 |
| Rights: | CC BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0 |
| رقم الانضمام: | edsbas.77FF2735 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15250016 15250024 |
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