Abstract | BACKGROUND:
Duchenne muscular 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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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 |
Journal | BMC neuroscience
(BMC Neurosci)
Vol. 8
Pg. 50
(Jul 08 2007)
ISSN: 1471-2202 [Electronic] England |
PMID | 17617925
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dystrophin
- Muscle Proteins
- Recombinant Fusion Proteins
- Viral Structural Proteins
- herpes simplex virus type 1 protein VP22
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Topics |
- Animals
- Cell Communication
(physiology)
- Dystrophin
(genetics, metabolism)
- Genetic Therapy
(methods)
- Mice
- Mice, Inbred mdx
- Muscle Proteins
(genetics, metabolism)
- Muscle, Skeletal
(metabolism, physiopathology)
- Muscular Dystrophy, Duchenne
(genetics, metabolism, therapy)
- NIH 3T3 Cells
- Plasmids
(genetics, metabolism)
- Protein Transport
(physiology)
- Recombinant Fusion Proteins
(genetics, metabolism)
- Transfection
(methods)
- Viral Structural Proteins
(genetics, metabolism)
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