Academic Journal
Chromosome Transplantation: A Possible Approach to Treat Human X-linked Disorders
| العنوان: | Chromosome Transplantation: A Possible Approach to Treat Human X-linked Disorders |
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| المؤلفون: | Marianna Paulis, Lucia Susani, Alessandra Castelli, Teruhiko Suzuki, Takahiko Hara, Letizia Straniero, Stefano Duga, Dario Strina, Stefano Mantero, Elena Caldana, Lucia Sergi Sergi, Anna Villa, Paolo Vezzoni |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 17, Iss , Pp 369-377 (2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | genomic disorders, induced pluripotent stem cells, genetic therapy, chromosome transfer, chromosome transplantation, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | Many human genetic diseases are associated with gross mutations such as aneuploidies, deletions, duplications, or inversions. For these “structural” disorders, conventional gene therapy, based on viral vectors and/or on programmable nuclease-mediated homologous recombination, is still unsatisfactory. To correct such disorders, chromosome transplantation (CT), defined as the perfect substitution of an endogenous defective chromosome with an exogenous normal one, could be applied. CT re-establishes a normal diploid cell, leaving no marker of the procedure, as we have recently shown in mouse pluripotent stem cells. To prove the feasibility of the CT approach in human cells, we used human induced pluripotent stem cells (hiPSCs) reprogrammed from Lesch-Nyhan (LN) disease patients, taking advantage of their mutation in the X-linked HPRT gene, making the LN cells selectable and distinguishable from the resistant corrected normal cells. In this study, we demonstrate, for the first time, that CT is feasible in hiPSCs: the normal exogenous X chromosome was first transferred using an improved chromosome transfer system, and the extra sex chromosome was spontaneously lost. These CT cells were functionally corrected and maintained their pluripotency and differentiation capability. By inactivation of the autologous HPRT gene, CT paves the way to the correction of hiPSCs from several X-linked disorders. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050120300140; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2020.01.003 |
| URL الوصول: | https://doaj.org/article/cafafd205a104ab4b7eb5032e65b38ea |
| رقم الانضمام: | edsdoj.fafd205a104ab4b7eb5032e65b38ea |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 |
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| DOI: | 10.1016/j.omtm.2020.01.003 |