Gene Therapy Progress and Prospects: Episomally maintained self-replicating systems

• Published in: Gene therapy Vol. 11; no. 24; pp. 1735 - 1741
• Main Authors: CONESE, M, AURICHE, C, ASCENZIONI, F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-12-2004
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Chromosomes; Chromosomes, Artificial - genetics; Epstein-Barr virus; Expression vectors; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene therapy; Genetic Therapy - methods; Genetic Therapy - trends; Genetic Vectors; Health. Pharmaceutical industry; Herpesvirus 4, Human - genetics; Humans; Industrial applications and implications. Economical aspects; Matrix attachment regions; Matrix Attachment Regions - genetics; Medical sciences; Packaging; Plasmids - genetics; Toxicity; Transfection; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vectors (Biology); Gammaherpesvirinae; Virus; artificial chromosomes; Herpesviridae; episomal; Epstein Barr virus; Epstein-Barr virus; scaffold/matrix attaching regions; Gene therapy; Artificial chromosome
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302362

The use of nonviral gene therapy vectors has been hampered by low level of transfection efficiency and lack of sustained gene expression. Episomal self-replicating systems may overcome these hurdles through their large packaging capacity, stability and reduced toxicity. This article reviews three classes of episomal molecules that have been tested with possible therapeutic genes: (1) self-replicating circular vectors, containing the Epstein-Barr virus (EBV) elements oriP and EBNA1; (2) small circular vectors containing scaffold/matrix attachment regions (S/MARs) as cis-acting elements to maintain the episomal status of the vector; (3) chromosomal vectors, based on the functional elements of the natural chromosomes. The studies reported validate the use of episomal vectors to obtain stable and prolonged gene expression, although reveal some limitations that necessitate additional work.