Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain tumor

A retroviral vector constructed from the murine leukemia virus (MLV) can on ly express transgenes in cells undergoing mitosis, indicating its suitabili ty as a delivery vehicle for cancer gene therapy. However, the transduction efficiency (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells was found to be unsatisfactory Recently, several researc h groups have demonstrated the feasibility of a retroviral vector pseudotyp ed with a vesicular stomatitis virus G (VSV-G) protein. In this study, the potential of VSV-G pseudotyped ML V-based retrovirus was examined as a deli very vehicle in a variety of human cancer cells including brain tumor cells in vitro and in vivo. The transduction efficiency of the 293T/G/GP/LacZ re trovirus in cell culture was superior in most cancer cells, particularly in brain tumor cells, compared with that of other retroviruses, such as PA317 - or PG13-derived. The relative growth rate and phosphatidylserine expressi on level on the plasma membrane of target cells mainly influenced the trans duction efficiency of VSV-G pseudotyped retrovirus, which suggested that bo th the relative growth rate and phosphatidylserine expression level were ma jor determinants of TE. Furthermore, 293T/G/GP/LacZ could efficiently trans duce human cancer cells regardless of the presence of chemical additives, w hereas in other retroviruses, cationic chemical additives such as polybrene or liposomes were essential during virus infection. Finally, an average of 10% gene expression was routinely obtained exclusively in the tumor mass w hen 293T/G/GP/LacZ concentrated by simple ultracentrifugation was directly administrated to pre-established brain tumors in animal models (U251-N nu/n u mice or C6 Wistar rats). All told, the present study suggests that the VS V-G pseudotyped retrovirus is a suitable vector for brain tumor gene therap y.