Chromosome-based Vectors

Group Members: Sören Turan, Niels Heinz

Contributing Principal Investigator: Bernd Schiedlmeier

Studies on the higher order organization of mammalian genes revealed the power of scaffold/matrix attachment regions (S/MARs) for designing novel systems for predictable and stable gene expression. In addition to their well established function as genomic insulators and enhancer support-elements, S/MARs support recombinase-mediated cassette exchange (RMCE) techniques, which in turn permit the marker-free introduction of genes into predetermined genomic targets. Based on their ORI-support function we could introduce the first example of a DNA-minicircle, which replicates, as an episome, for several hundred generations in the absence of selection pressure and without support of a virally encoded factor. Obviously, the S/MAR recruits the endogenous replication and segregation apparatus of the host cell enabling the design of entirely novel tools for gene therapy and the systematic modification of ES- and iPS- cells. A primary goal is the efficient transfer of both, exchange vectors and minicircles, by epiretroviral transfer techniques.