Plasmid Vectors
Novel plasmids for controlled and sustained transgene expression
Plasmid based gene therapy approaches often lack long term transgene expression in vivo due to silencing or loss of the vector. One way to overcome these limitations is to combine non-silenced promoters with strong viral enhancers. Here we combine strong enhancer and promoter elements devoid of potentially immunostimulating CpG sequences for sustained long term expression in vivo. Tumor selective transgene expression is achieved utilizing tumor cell specific promoter elements. So far we could show high and long lasting transgene expression either in liver tissue after hydrodynamic delivery of plasmid or in tumors after systemic application of polyplexes. Luciferase transgene signal is monitored by bioluminescence in vivo imaging. Such optimized plasmids are then used in therapeutic studies.
References
- Haase R, Magnusson T, Su B, Kopp F, Wagner E, Lipps H, Baiker A, Ogris M (2013) Generation of a tumor- and tissue-specific episomal non-viral vector system. BMC Biotechnol. 2013 Jun 4;13(1):49. [Epub ahead of print]
- Magnusson, T., Haase, R., Schleef, M., Wagner, E., Ogris, M. (2011) Sustained, high transgene expression in liver with plasmid vectors using optimized promoter-enhancer combinations, J Gene Med. 2011 Jul;13(7-8):382-91
- Haase, R., Argyros, O., Wong, S.P., Harbottle, R.P., Lipps, H.J., Ogris, M., Magnusson, T., Vizoso Pinto, M.G., Haas, J., Baiker, A. (2010) pEPito: a significantly improved non-viral episomal expression vector for mammalian cells, BMC Biotechnology 2010 Mar 15;10:20