| Prospects for the use of artificial chromosomes and minichromosome-like episomes in gene therapy. | |
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MedLine Citation:
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PMID: 20862363 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Artificial chromosomes and minichromosome-like episomes are large DNA molecules capable of containing whole genomic loci, and be maintained as nonintegrating, replicating molecules in proliferating human somatic cells. Authentic human artificial chromosomes are very difficult to engineer because of the difficulties associated with centromere structure, so they are not widely used for gene-therapy applications. However, OriP/EBNA1-based episomes, which they lack true centromeres, can be maintained stably in dividing cells as they bind to mitotic chromosomes and segregate into daughter cells. These episomes are more easily engineered than true human artificial chromosomes and can carry entire genes along with all their regulatory sequences. Thus, these constructs may facilitate the long-term persistence and physiological regulation of the expression of therapeutic genes, which is crucial for some gene therapy applications. In particular, they are promising vectors for gene therapy in inherited diseases that are caused by recessive mutations, for example haemophilia A and Friedreich's ataxia. Interestingly, the episome carrying the frataxin gene (deficient in Friedreich's ataxia) has been demonstrated to rescue the susceptibility to oxidative stress which is typical of fibroblasts from Friedreich's ataxia patients. This provides evidence of their potential to treat genetic diseases linked to recessive mutations through gene therapy. |
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Authors:
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Sara Pérez-Luz; Javier Díaz-Nido |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-24 |
Journal Detail:
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Title: Journal of biomedicine & biotechnology Volume: 2010 ISSN: 1110-7251 ISO Abbreviation: J. Biomed. Biotechnol. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-09-23 Completed Date: 2011-01-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101135740 Medline TA: J Biomed Biotechnol Country: United States |
Other Details:
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Languages: eng Pagination: - Citation Subset: IM |
Affiliation:
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Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain. spluz@cbm.uam.es |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Chromosomes, Artificial, Human
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genetics* DNA-Binding Proteins / genetics, metabolism Epstein-Barr Virus Nuclear Antigens / genetics* Friedreich Ataxia / therapy Gene Expression* Gene Therapy / methods* Hemophilia A / therapy Herpesvirus 4, Human / genetics Humans Iron-Binding Proteins / genetics, therapeutic use Plasmids / genetics* |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/EBV-encoded nuclear antigen 1; 0/Epstein-Barr Virus Nuclear Antigens; 0/Iron-Binding Proteins; 0/frataxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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