Development of a new S/MAR containing Minicircle DNA vector: a new promise for Gene Therapy.

Abstract

A barrier limiting the use of nonviral vectors for gene therapy is related to the short duration of transgene expression in vivo. Development, evaluation, and optimisation of a long term transgene expression using a non viral vector is currently the primary aim in our research field. Recently, we have demonstrate that a nonviral episomal plasmid (pDNA) vector combined with a scaffold/matrix attachment region (S/MAR) is able to sustain long-term expression in murine liver for at least six months following hydrodynamic injection. However, plasmids contain sequences, which are essential for propagation in bacteria but are unnecessary for expression in mammalian cells. These bacterial components are responsible for the epigenetic silencing of the vector and toxicity when applied in vivo.