Oncoretrovirus and lentivirus vectors pseudotyped with lymphocytic choriomeningitis virus glycoprotein: Generation, concentration, and broad host range

被引:138
作者
Beyer, WR
Westphal, M
Ostertag, W
von Laer, D
机构
[1] Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany
[2] Univ Krankenhaus Eppendorf, Neurochirurg Klin, D-20251 Hamburg, Germany
[3] Georg Speyer Haus, D-60596 Frankfurt, Germany
关键词
D O I
10.1128/JVI.76.3.1488-1495.2002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Lymphocytic choriomeningitis virus (LCMV) is a noncytopathic. arenavirus shown to infect a broad range of different cell types. Here, we combined the beneficial characteristics of the LCMV glycoprotein (LCMV-GP) and those of retroviral vectors to generate a new, safe, and efficient gene transfer system. These LCMV-GP pseudotypes were systematically compared with vectors, containing the widely used amphotropic murine leukemia virus envelope (A-MLVenv) or the vesicular stomatitis virus G protein (VSV-G). Production of LCMV-GP-pseudotyped oncoretroviral and lentiviral vectors by transient transfection resulted in vector titers similar to those with A-MLVenv or VSV-G. In contrast to A-MLVenv particles, LCMV-GP pseudotypes could be efficiently concentrated by ultracentrifugation without loss of vector titer. Unlike the cell-toxic VSV-G, a stable retroviral packaging cell line constitutively expressing LCMV-GP could be established. Vectors pseudotyped with LCMV-GP efficiently transduced many cell lines from different species and tissues relevant for gene therapy. Transduction of human glioma cells was studied in detail. These cells are a major target for cancer gene therapy and were transduced more efficiently with LCMV-GP-pseudotyped vectors than with the generally used A-MLVenv particles. The high stability, low toxicity, and broad host range make LCMV-GP-pseudotyped vectors attractive for gene transfer applications. The recombinant LCMV-GP-pseudotyped vectors will also allow functional characterization of naturally occurring and recombinant LCMV-GP variants.
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页码:1488 / 1495
页数:8
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