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Journal articles
Ex Vivo Selection of Transduced Hematopoietic Stem Cells for Gene Therapy of β-Hemoglobinopathies
Kanit Bhukhai
1, 2
Edouard de Dreuzy
1, 2
Marie Giorgi
1, 2
Charlotte Colomb
1, 2
Olivier Negre
1, 3, 2
Maria Denaro
3
Beatrix Gillet-Legrand
1, 4, 2
Joëlle Cheuzeville
1, 4, 2
Anaïs Paulard
1, 4, 2
Hélène Trebeden-Negre
5
Suparerk Borwornpinyo
6
Karine Sii-Felice
1, 2
Leila Maouche
1, 2
Julian Down
7
Phillippe Leboulch
1, 2, 8, 9, *
Emmanuel Payen
1, 2, *
*
Corresponding author
Kanit Bhukhai 1, 2
Author
Edouard de Dreuzy 1, 2
Author
Marie Giorgi 1, 2
Author
Charlotte Colomb 1, 2
Author
Olivier Negre 1, 3, 2
Author
Maria Denaro 3
Author
Beatrix Gillet-Legrand 1, 4, 2
Author
Joëlle Cheuzeville 1, 4, 2
Author
Anaïs Paulard 1, 4, 2
Author
Hélène Trebeden-Negre 5
Author
Suparerk Borwornpinyo 6
Author
Karine Sii-Felice 1, 2
Author
Leila Maouche 1, 2
Author
Julian D Down 7
Author
Phillippe Leboulch 1, 2, 8, 9
Correspondent author
Emmanuel Payen 1, 2
Correspondent author
1
IMETI - Institut des Maladies Emergentes et des Thérapies Innovantes (France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives : DSV/IMETI (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
- Université Paris-Saclay (Espace Technologique, Bat. Discovery - RD 128 - 2e ét., 91190 Saint-Aubin - France)
2
UMR E007 - Thérapie génique et contrôle de l'expansion cellulaire (anciennement U962. CEA Fontenay BP 6 92265 FONTENAY AUX ROSES - France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives : DRF/IMETI (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
- Université Paris-Saclay (Espace Technologique, Bat. Discovery - RD 128 - 2e ét., 91190 Saint-Aubin - France)
3
Bluebird bio, Inc (formerly Genetix Pharmaceuticals
[Cambridge, MA, USA] - United States)
4
Bluebird bio France [Fontenay aux Roses] (France)
5
CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- Sorbonne Université (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
6
Mahidol University [Bangkok, Thailand] (Thailand)
7
Institute for Medical Engineering and Science [Cambridge, MA, USA] (United States)
- MIT - Massachusetts Institute of Technology (77 Massachusetts Ave, Cambridge, MA 02139 - United States)
8
Ramathibodi Hospital [Bangkok, Thailand] (Thailand)
9
HMS - Harvard Medical School [Boston] (25 Shattuck Street Boston, MA 02115 - United States)
Abstract : Although gene transfer to hematopoietic stem cells (HSCs) has shown therapeutic efficacy in recent trials for several individuals with inherited disorders, transduction incompleteness of the HSC population remains a hurdle to yield a cure for all patients with reasonably low integrated vector numbers. In previous attempts at HSC selection, massive loss of transduced HSCs, contamination with non-transduced cells, or lack of applicability to large cell populations has rendered the procedures out of reach for human applications. Here, we fused codon-optimized puromycin N-acetyltransferase to herpes simplex virus thymidine kinase. When expressed from a ubiquitous promoter within a complex lentiviral vector comprising the b AT87Q-globin gene, viral titers and therapeutic gene expression were maintained at effective levels. Complete selection and preservation of transduced HSCs were achieved after brief exposure to puromycin in the presence of MDR1 blocking agents, suggesting the procedure's suitability for human clinical applications while affording the additional safety of conditional suicide.
Document type :
Journal articles
Complete list of metadatas
https://www.hal.inserm.fr/inserm-01834780
Contributor : Emmanuel Payen <>
Submitted on : Tuesday, July 10, 2018 - 11:24:44 PM
Last modification on : Friday, December 11, 2020 - 3:50:01 AM
Long-term archiving on: : Thursday, October 11, 2018 - 2:24:29 PM
Contributor : Emmanuel Payen <>
Submitted on : Tuesday, July 10, 2018 - 11:24:44 PM
Last modification on : Friday, December 11, 2020 - 3:50:01 AM
Long-term archiving on: : Thursday, October 11, 2018 - 2:24:29 PM
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Bhukhai et al.pdf
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Identifiers
- HAL Id : inserm-01834780, version 1
- DOI : 10.1016/j.ymthe.2017.10.015
- PUBMED : 29221807
- PUBMEDCENTRAL : PMC5835017
Citation
Kanit Bhukhai, Edouard de Dreuzy, Marie Giorgi, Charlotte Colomb, Olivier Negre, et al.. Ex Vivo Selection of Transduced Hematopoietic Stem Cells for Gene Therapy of β-Hemoglobinopathies. Molecular Therapy, Nature Publishing Group, 2018, 26 (2), pp.480 - 495. ⟨10.1016/j.ymthe.2017.10.015⟩. ⟨inserm-01834780⟩
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