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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 642804, 16 pages
http://dx.doi.org/10.1155/2010/642804
Review Article

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

1Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain
2Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), C/Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049 Madrid, Spain
3U-748, Area de Neurogenética, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain

Received 19 February 2010; Revised 2 June 2010; Accepted 5 July 2010

Academic Editor: Rudi Beyaert

Copyright © 2010 Sara Pérez-Luz and Javier 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.

Abstract

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.