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

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.

• 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)

Chemical References

• Dystrophin
• Muscle Proteins
• Recombinant Fusion Proteins
• Viral Structural Proteins
• herpes simplex virus type 1 protein VP22

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)