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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver
Journal of Molecular Medicine, Volume 89, No. 5, Year 2011
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Description
We have previously described the development of a scaffold/matrix attachment region (S/MAR) episomal vector system for in vivo application and demonstrated its utility to sustain transgene expression in the mouse liver for at least 6 months following a single administration. Subsequently, we observed that transgene expression is sustained for the lifetime of the animal. The level of expression, however, does drop appreciably over time. We hypothesised that by eliminating the bacterial components in our vectors, we could improve their performance since bacterial sequences have been shown to be responsible for the immunotoxicity of the vector and the silencing of its expression when applied in vivo. We describe here the development of a minimally sized S/MAR vector, which is devoid of extraneous bacterial sequences. This minicircle vector comprises an expression cassette and an S/MAR moiety, providing higher and more sustained transgene expression for several months in the absence of selection, both in vitro and in vivo. In contrast to the expression of our original S/MAR plasmid vector, the novel S/MAR minicircle vectors mediate increased transgene expression, which becomes sustained at about twice the levels observed immediately after administration. These promising results demonstrate the utility of minimally sized S/MAR vectors for persistent, atoxic gene expression. © 2011 Springer-Verlag.
Authors & Co-Authors
Argyros, Orestis
United Kingdom, London
Imperial College London
Waddington, Simon N.
United Kingdom, London
University College London
Howe, Steven J.
United Kingdom, London
University College London
Niceta, Marcello
United Kingdom, London
Imperial College London
Coutelle, Charles C.
United Kingdom, London
Imperial College London
Statistics
Citations: 68
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1007/s00109-010-0713-3
ISSN:
09462716
Research Areas
Genetics And Genomics