title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China. xf7803@yahoo.com.cn <xf7803@yahoo.com.cn>
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
authors.forename: Meijuan
authors.initials: M
authors.lastname: Yu
authors.forename: Wanyi
authors.initials: W
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.forename: Yanchang
authors.initials: Y
authors.lastname: Shang
authors.forename: Funing
authors.initials: F
authors.lastname: Peng
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhao
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhou
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.forename: Liurong
authors.initials: L
authors.lastname: Fang
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Chamberlain
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D018101:Mice, Inbred mdx; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016189:Dystrophin; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22