Improved gene transfer techniques have been instrumental for the progress toward human gene therapy. The most commonly used transfer vectors in clinical applications are derived from retroviruses. These vectors can provide stable gene transfer and expression in mammalian cells, and packaging cell lines have been developed, which safely produce replication-incompetent vectors. A major factor that determines the stabilities and host ranges of such vectors is the retroviral glycoprotein in the outer lipid envelope of the vector particle.

We improved the stability and transduction efficiency of retroviral vectors by pseudotyping the particles with glycoproteins of other viruses. Especially, we developed and characterized retroviral pseudotypes with lymphocytic choriomeningitis virus glycoproteins (LCMV-GP). The high stability, low toxicity, and broad host range make these LCMV-GP pseudotyped vectors attractive for various gene transfer applications. We also used the recombinant pseudotyped vectors for the functional characterization of LCMV-GP.

In other projects we generate alternative retroviral pseudotypes for the analysis of the specific viral glycoproteins and the viral entry..

    wbey@virologie.mh-hannover.de

    lpok@virologie.mh-hanover.de

Beyer, W. R., H. Miletic, W. Ostertag, and D. von Laer. 2001. "Recombinant expression of the lymphocytic choriomeningitis virus (WE) glycoproteins: A single amino acid makes the difference." J. Virol. 75: 1061-1064.

Beyer, W. R., M. Westphal, W. Ostertag, and D. von Laer. 2002. "Oncoretroviral and lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoprotein: generation, concentration and broad host range." J. Virol. 76: 1488-1495.

Fehse, B., O. S. Kustikova, Z. Li, A. Wahlers, W. Bohn, W. R. Beyer, D. Chalmers, P. Tiberghien, K. Kühlcke, A. R. Zander, and C. Baum. 2002. "A novel 'sort-suicide' fusion gene vector for T cell manipulation." Gene Ther. 9: 1633-1638.

Beyer, W. R., D. Pöpplau, W. Garten, D. von Laer, and O. Lenz. 2003. "Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI 1/S1P. J. Virol. (in press)