Gene therapy progress and prospects: episomally maintained self-replicating systems
- PMID:15385951
- DOI: 10.1038/sj.gt.3302362
Gene therapy progress and prospects: episomally maintained self-replicating systems
Abstract
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.
Similar articles
- Gene transfer into human hematopoietic progenitor cells with an episomal vector carrying an S/MAR element.Papapetrou EP, Ziros PG, Micheva ID, Zoumbos NC, Athanassiadou A.Papapetrou EP, et al.Gene Ther. 2006 Jan;13(1):40-51. doi: 10.1038/sj.gt.3302593.Gene Ther. 2006.PMID:16094410
- Suitability of Epstein-Barr virus-based episomal vectors for expression of cytokine genes in human lymphoma cells.Mũcke S, Polack A, Pawlita M, Zehnpfennig D, Massoudi N, Bohlen H, Doerfler W, Bornkamm G, Diehl V, Wolf J.Mũcke S, et al.Gene Ther. 1997 Feb;4(2):82-92. doi: 10.1038/sj.gt.3300363.Gene Ther. 1997.PMID:9081710
- An enhanced EBNA1 variant with reduced IR3 domain for long-term episomal maintenance and transgene expression of oriP-based plasmids in human cells.Wendelburg BJ, Vos JM.Wendelburg BJ, et al.Gene Ther. 1998 Oct;5(10):1389-99. doi: 10.1038/sj.gt.3300736.Gene Ther. 1998.PMID:9930345
- Genetic modification of hematopoietic stem cells with nonviral systems: past progress and future prospects.Papapetrou EP, Zoumbos NC, Athanassiadou A.Papapetrou EP, et al.Gene Ther. 2005 Oct;12 Suppl 1:S118-30. doi: 10.1038/sj.gt.3302626.Gene Ther. 2005.PMID:16231044Review.
- Exploiting chromosomal and viral strategies: the design of safe and efficient non-viral gene transfer systems.Lipps HJ, Bode J.Lipps HJ, et al.Curr Opin Mol Ther. 2001 Apr;3(2):133-41.Curr Opin Mol Ther. 2001.PMID:11338925Review.
Cited by
- E2F in vivo binding specificity: comparison of consensus versus nonconsensus binding sites.Rabinovich A, Jin VX, Rabinovich R, Xu X, Farnham PJ.Rabinovich A, et al.Genome Res. 2008 Nov;18(11):1763-77. doi: 10.1101/gr.080622.108. Epub 2008 Oct 3.Genome Res. 2008.PMID:18836037Free PMC article.
- An S/MAR-based infectious episomal genomic DNA expression vector provides long-term regulated functional complementation of LDLR deficiency.Lufino MM, Manservigi R, Wade-Martins R.Lufino MM, et al.Nucleic Acids Res. 2007;35(15):e98. doi: 10.1093/nar/gkm570. Epub 2007 Aug 2.Nucleic Acids Res. 2007.PMID:17675302Free PMC article.
- Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.Ago Y, Rintz E, Musini KS, Ma Z, Tomatsu S.Ago Y, et al.Int J Mol Sci. 2024 Jan 17;25(2):1113. doi: 10.3390/ijms25021113.Int J Mol Sci. 2024.PMID:38256186Free PMC article.Review.
- Artificial and engineered chromosomes: developments and prospects for gene therapy.Grimes BR, Monaco ZL.Grimes BR, et al.Chromosoma. 2005 Sep;114(4):230-41. doi: 10.1007/s00412-005-0017-5. Epub 2005 Oct 15.Chromosoma. 2005.PMID:16133351Review.
- Dominant-negative effects of COL7A1 mutations can be rescued by controlled overexpression of normal collagen VII.Fritsch A, Spassov S, Elfert S, Schlosser A, Gache Y, Meneguzzi G, Bruckner-Tuderman L.Fritsch A, et al.J Biol Chem. 2009 Oct 30;284(44):30248-56. doi: 10.1074/jbc.M109.045294. Epub 2009 Sep 2.J Biol Chem. 2009.PMID:19726672Free PMC article.
Publication types
MeSH terms
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous