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Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport

Fu Xiong12, Shaobo Xiao3, Meijuan Yu2, Wanyi Li2, Hui Zheng1, Yanchang Shang1, Funing Peng1, Cuiping Zhao1, Wenliang Zhou4, Huanchun Chen3, Liurong Fang3, Jeffrey S Chamberlain5 and Cheng Zhang12*

Author Affiliations

1 Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R.China

2 Center for Stem Cell Biology and Tissue Engineering of Sun Yat-sen University, Guangzhou 510080, P.R.China

3 State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, P.R.China

4 Lab Of Physiology, Life sciences School of Sun Yat-sen University, Guangzhou 510080, P.R.China

5 Department of Neurology, University of Washington School of Medicine, Seattle, WA 98195-7720, USA

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BMC Neuroscience 2007, 8:50  doi:10.1186/1471-2202-8-50

Published: 8 July 2007



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. Plasmid-mediated 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.


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.


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.