S/MAR VECTORS — ALTERNATIVE EXPRESSION SYSTEMS FOR GENE THERAPY?

Abstract

Due to the lack of natural occurring plasmids in higher eukaryotes, most vectors currently used for the modification of mammalian cells and organisms are based on modified viruses. But the use of these virus-based vectors still has severe safety risks and therefore considerable efforts are made to design alternative vector systems, whose function are based on chromosomal elements and which behave as an autonomous unit in the cell. The construction of episomal vectors was hindered by our limited knowledge of the epigenetic regulation of replication in higher eukaryotes.However, in the late 1990, a prototype non-viral episomal vector was constructed which replicates autonomously in all mammalian cells and is mitotically stable in the absence of selection. Its function relies on an expression unit linked to a scaffold/matrix-attached region (S/MAR). In this short review, we describe the rational of its construction and functioning. The prototype vector was improved within the past years with respect to establishment and expression efficiency and has now been tested for various preclinical applications. Eventually, S/MAR-based vectors will be improved to such a stage that they can provide a safe alternative to viral vectors to be used in gene therapy.