دورية أكاديمية
Improved engraftment and therapeutic efficacy by human genome-edited hematopoietic stem cells with Busulfan-based myeloablation
| العنوان: | Improved engraftment and therapeutic efficacy by human genome-edited hematopoietic stem cells with Busulfan-based myeloablation |
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| المؤلفون: | Edina Poletto, Pasqualina Colella, Luisa N. Pimentel Vera, Shaukat Khan, Shunji Tomatsu, Guilherme Baldo, Natalia Gomez-Ospina |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 25, Iss , Pp 392-409 (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | genome editing, CRISPR-Cas9, hematopoietic stem cell, Busulfan, total body irradiation, engraftment, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | Autologous hematopoietic stem cell transplantation using genome-edited cells can become a definitive therapy for hematological and non-hematological disorders with neurological involvement. Proof-of-concept studies using human genome-edited hematopoietic stem cells have been hindered by the low efficiency of engraftment of the edited cells in the bone marrow and their modest efficacy in the CNS. To address these challenges, we tested a myeloablative conditioning regimen based on Busulfan in an immunocompromised model of mucopolysaccharidosis type 1. Compared with sub-lethal irradiation, Busulfan conditioning enhanced the engraftment of edited CD34+ cells in the bone marrow, as well the long-term homing and survival of bone-marrow-derived cells in viscera, and in the CNS, resulting in higher transgene expression and biochemical correction in these organs. Edited cell selection using a clinically compatible marker resulted in a population with low engraftment potential. We conclude that conditioning can impact the engraftment of edited hematopoietic stem cells. Furthermore, Busulfan-conditioned recipients have a higher expression of therapeutic proteins in target organs, particularly in the CNS, constituting a better conditioning approach for non-hematological diseases with neurological involvement. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050122000572; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2022.04.009 |
| URL الوصول: | https://doaj.org/article/138467156b384541b8cb54764f091280 |
| رقم الأكسشن: | edsdoj.138467156b384541b8cb54764f091280 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 |
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| DOI: | 10.1016/j.omtm.2022.04.009 |