A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy

被引:55
作者
Diaz, RM
Bateman, A
Emiliusen, L
Fielding, A
Trono, D
Russell, SJ
Vile, RG
机构
[1] Mayo Clin, Program Mol Med, Rochester, MN 55905 USA
[2] Univ Geneva, CMU, Dept Genet & Microbiol, Geneva, Switzerland
关键词
lentiviral vectors; cancer; fusogenic proteins; suicide genes;
D O I
10.1038/sj.gt.3301277
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The gibbon ape leukaemia virus envelope fusogenic membrane glycoprotein (GALV FMG) is a highly potent cytotoxic gene with great potential for use in cancer gene therapy. Here, we show that production of a VSV-G pseudotyped lentiviral vector expressing GALV FMG reconciles the requirements of viral production with the cytotoxic effects of GALV in human cells and has high titres on both dividing and quiescent tumour cells. Direct intratumoral injection of these stocks eradicated progressively growing human tumour xenografts. The potent bystander effect of the FMG transgene is a major contributor to the success of this approach but immunological activation may also be a factor. To our knowledge, this is the first demonstration in vivo of the potential both of FMG and lentiviral vectors for cancer gene therapy and highlights the importance of exploring different Vector systems to complement the biological properties of the therapeutic transgene.
引用
收藏
页码:1656 / 1663
页数:8
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