Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy
Joint Authors
Pérez-Luz, Sara
Díaz-Nido, Javier
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2009), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-07-20
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Pérez-Luz, Sara& Díaz-Nido, Javier. 2010. Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy. BioMed Research International،Vol. 2010, no. 2010, pp.1-16.
https://search.emarefa.net/detail/BIM-989051
Modern Language Association (MLA)
Pérez-Luz, Sara& Díaz-Nido, Javier. Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy. BioMed Research International No. 2010 (Dec. 2010), pp.1-16.
https://search.emarefa.net/detail/BIM-989051
American Medical Association (AMA)
Pérez-Luz, Sara& Díaz-Nido, Javier. Prospects for the Use of Artificial Chromosomes and Minichromosome-Like Episomes in Gene Therapy. BioMed Research International. 2010. Vol. 2010, no. 2010, pp.1-16.
https://search.emarefa.net/detail/BIM-989051
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-989051