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

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 wi...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1931604/
https://www.ncbi.nlm.nih.gov/pubmed/17617925
http://dx.doi.org/10.1186/1471-2202-8-50
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author 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
author_facet 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
author_sort Xiong, Fu
collection PubMed
description 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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spelling pubmed-19316042007-07-25 Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport 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 BMC Neurosci Research Article 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. BioMed Central 2007-07-08 /pmc/articles/PMC1931604/ /pubmed/17617925 http://dx.doi.org/10.1186/1471-2202-8-50 Text en Copyright © 2007 Xiong et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
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
Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
title Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
title_full Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
title_fullStr Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
title_full_unstemmed Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
title_short Enhanced effect of microdystrophin gene transfection by HSV-VP22 mediated intercellular protein transport
title_sort enhanced effect of microdystrophin gene transfection by hsv-vp22 mediated intercellular protein transport
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1931604/
https://www.ncbi.nlm.nih.gov/pubmed/17617925
http://dx.doi.org/10.1186/1471-2202-8-50
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