A retroviral vector constructed from the murine leukemia virus (MLV) can only express transgenes in cells undergoing mitosis, indicating its suitability 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 research groups have demonstrated the feasibility of a retroviral vector pseudotyped with a
vesicular stomatitis virus G (VSV-
G) protein. In this study, the potential of VSV-G pseudotyped MLV-based retrovirus was examined as a delivery 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 retrovirus 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 expression level on the plasma membrane of target cells mainly influenced the transduction efficiency of VSV-G pseudotyped retrovirus, which suggested that both the relative growth rate and
phosphatidylserine expression level were major determinants of TE. Furthermore, 293T/G/GP/LacZ could efficiently transduce human
cancer cells regardless of the presence of chemical additives, whereas 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 when 293T/G/GP/LacZ concentrated by simple ultracentrifugation was directly administrated to pre-established
brain tumors in animal models (U251-N nu/nu mice or C6 Wistar rats). All told, the present study suggests that the VSV-G pseudotyped retrovirus is a suitable vector for
brain tumor gene therapy.