Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
View/ Open
Date
2007Author
Xiong, Fu
Xiao, Shaobo
Yu, Meijuan
Li, Wanyi
Zheng, Hui
Shang, Yanchang
Peng, Funing
Zhao, Cuiping
Zhou, Wenliang
Chen, Huanchun
Fang, Liurong
Chamberlain, Jeffrey S.
Zhang, Cheng
Metadata
Show full item recordAbstract
Background: Duchenne musclar dystrophy (DMD) is an X-linked recessive disease caused by mutations of dystrophin gene, there is no effective treatment for this disorder at present. Plasmidmediated
gene therapy is a promising therapeutical approach for the treatment of DMD. One of
the major issues with plasmid-mediated gene therapy for DMD is poor transfection efficiency and distribution. The herpes simplex virus protein VP22 has the capacity to spread from a primary
transduced cell to surrounding cells and improve the outcome of gene transfer. To improve the efficiency of plasmid-mediated gene therapy and investigate the utility of the intercellular trafficking
properties of VP22-linked protein for the treatment for DMD, expression vectors for C-terminal versions of VP22-microdystrophin fusion protein was constructed and the VP22-mediated shuttle effect was evaluated both in vitro and in vivo.
Results: Our results clearly demonstrate that the VP22-microdystrophin fusion protein could transport into C2C12 cells from 3T3 cells, moreover, the VP22-microdystrophin fusion protein
enhanced greatly the amount of microdystrophin that accumulated following microdystrophin gene
transfer in both transfected 3T3 cells and in the muscles of dystrophin-deficient (mdx) mice.
Conclusion: These results highlight the efficiency of the VP22-mediated intercellular protein delivery for potential therapy of DMD and suggested that protein transduction may be a potential
and versatile tool to enhance the effects of gene delivery for somatic gene therapy of DMD.