Foamy viruses (FV) were only lately successfully introduced into the repertoire of vector systems for the correction of inherited diseases of the hematopoietic system. Nevertheless, some of their unique features, including their apparent apathogenicity as well as their efficient transduction capability for hematopoietic stem cells, make them one of the most promising tools for various gene therapeutic approaches. We developed an expression-optimized replication-deficient FV vector system allowing production of vector titers up to 107 IU/ml without concentration. Furthermore, lentiviral and gammaretroviral vector systems for highly efficient pseudotyping by FV Env were developed facilitating gene transfer into various target tissues with efficiencies exceeding that of corresponding standard VSV-G pseudotypes. Finally, we generated functional, autofluorescent protein (AFP)-tagged FV particles that allow the characterization of various steps of FV vector entry by modern live-cell microscopy techniques.
In collaboration with several labs of the SPP program a combination of different fluorescent microscopy analysis techniques, as wells as genetic-, and biochemical methods will be used to (1) characterize late steps of FV vector entry in different target cells, (2) establish a FV vector system for genetic complementation by homologous recombination and/or specific integration site targeting, and (3) evaluate approaches for tissue specific transduction of retroviral vectors based on chimeric FV glycoproteins.

top