Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport |
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Authors: | Fu Xiong Shaobo Xiao Meijuan Yu Wanyi Li Hui Zheng Yanchang Shang Funing Peng Cuiping Zhao Wenliang Zhou Huanchun Chen Liurong Fang Jeffrey S Chamberlain Cheng Zhang |
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Institution: | 1. Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, P.R.China 2. Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, 510080, Guangzhou, P.R.China 3. State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, 430070, Wuhan, P.R.China 4. Lab Of Physiology, Life sciences School Sun Yat-sen University, 510080, Guangzhou, P.R.China 5. Department of Neurology, University of Washington School of Medicine, 98195-7720, Seattle, WA, USA
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Abstract: | 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. 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. 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. |
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