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Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy

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...

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Autores principales: Pérez-Luz, Sara, Díaz-Nido, Javier
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938438/
https://www.ncbi.nlm.nih.gov/pubmed/20862363
http://dx.doi.org/10.1155/2010/642804
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author Pérez-Luz, Sara
Díaz-Nido, Javier
author_facet Pérez-Luz, Sara
Díaz-Nido, Javier
author_sort Pérez-Luz, Sara
collection PubMed
description 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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spelling pubmed-29384382010-09-22 Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy Pérez-Luz, Sara Díaz-Nido, Javier J Biomed Biotechnol Review Article 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. Hindawi Publishing Corporation 2010 2010-08-24 /pmc/articles/PMC2938438/ /pubmed/20862363 http://dx.doi.org/10.1155/2010/642804 Text en Copyright © 2010 S. Pérez-Luz and J. Díaz-Nido. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Pérez-Luz, Sara
Díaz-Nido, Javier
Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy
title Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy
title_full Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy
title_fullStr Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy
title_full_unstemmed Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy
title_short Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy
title_sort prospects for the use of artificial chromosomes and minichromosome-like episomes in gene therapy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938438/
https://www.ncbi.nlm.nih.gov/pubmed/20862363
http://dx.doi.org/10.1155/2010/642804
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