[Construction of recombinant plasmid pVAX1-microdystrophin and preliminary study on the treatment to Duchenne muscular dystrophy]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Dec;25(6):624-8.
[Article in Chinese]

Abstract

Objective: To construct the recombinant plasmid containing human microdystrophin cDNA, and study the microdystrophin expression in vivo and in vitro.

Methods: Microdystrophin cDNA was obtained from recombinant plasmid pBSK-MICRO digested with restrictive endonuclease Not I, the product was inserted into plasmid pVAX1, resulting in pAMICDYS. And then 3T3 cells were transfected with pAMICDYS. Forty-eight hours after transfection, the expression of the microdystrophin was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. Finally, TA muscles of mdx mice were injected with the recombinant plasmid pAMICDYS through i.m. and the pathological change of TA was evaluated by histology, and the expression of microdystrophin in mdx TA was detected by immunohistochemical analysis.

Results: The recombinant plasmid containing human microdystrophin cDNA was constructed successfully. The recombinant plasmid was proved to be able to express microdystrophin protein both in vivo and in vitro. Moreover, treatment of the TA of mdx mice with the recombinant plasmid could decrease the number of centrally nucleated myofibers.

Conclusion: Recombinant plasmid containing the microdystrophin gene was constructed successfully, and it could express microdystrophin protein both in vivo and in vitro. It provides basis for further study on microdystrophin as a target gene to treat Duchenne muscular dystrophy (DMD) by electrotransfer, i.v, arterial injection and combining with other exogenous gene to enhance microdystrophin expression.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cloning, Molecular
  • DNA Restriction Enzymes / metabolism
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • DNA, Recombinant / genetics*
  • DNA, Recombinant / metabolism
  • Dystrophin / genetics*
  • Gene Expression
  • Genetic Engineering
  • Genetic Therapy
  • Genetic Vectors / metabolism
  • Humans
  • Immunohistochemistry
  • Mice
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / therapy*
  • NIH 3T3 Cells
  • Plasmids / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • DNA, Complementary
  • DNA, Recombinant
  • Dystrophin
  • DNA Restriction Enzymes