Skip to main content

Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy.

Publication ,  Journal Article
Harper, SQ; Hauser, MA; DelloRusso, C; Duan, D; Crawford, RW; Phelps, SF; Harper, HA; Robinson, AS; Engelhardt, JF; Brooks, SV; Chamberlain, JS
Published in: Nat Med
March 2002

Attempts to develop gene therapy for Duchenne muscular dystrophy (DMD) have been complicated by the enormous size of the dystrophin gene. We have performed a detailed functional analysis of dystrophin structural domains and show that multiple regions of the protein can be deleted in various combinations to generate highly functional mini- and micro-dystrophins. Studies in transgenic mdx mice, a model for DMD, reveal that a wide variety of functional characteristics of dystrophy are prevented by some of these truncated dystrophins. Muscles expressing the smallest dystrophins are fully protected against damage caused by muscle activity and are not morphologically different from normal muscle. Moreover, injection of adeno-associated viruses carrying micro-dystrophins into dystrophic muscles of immunocompetent mdx mice results in a striking reversal of histopathological features of this disease. These results demonstrate that the dystrophic pathology can be both prevented and reversed by gene therapy using micro-dystrophins.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

March 2002

Volume

8

Issue

3

Start / End Page

253 / 261

Location

United States

Related Subject Headings

  • Protein Conformation
  • Muscular Dystrophy, Duchenne
  • Muscle, Skeletal
  • Mice, Transgenic
  • Mice, Inbred mdx
  • Mice
  • Male
  • Immunology
  • Immunohistochemistry
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Harper, S. Q., Hauser, M. A., DelloRusso, C., Duan, D., Crawford, R. W., Phelps, S. F., … Chamberlain, J. S. (2002). Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med, 8(3), 253–261. https://doi.org/10.1038/nm0302-253
Harper, Scott Q., Michael A. Hauser, Christiana DelloRusso, Dongsheng Duan, Robert W. Crawford, Stephanie F. Phelps, Hollie A. Harper, et al. “Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy.Nat Med 8, no. 3 (March 2002): 253–61. https://doi.org/10.1038/nm0302-253.
Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, et al. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med. 2002 Mar;8(3):253–61.
Harper, Scott Q., et al. “Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy.Nat Med, vol. 8, no. 3, Mar. 2002, pp. 253–61. Pubmed, doi:10.1038/nm0302-253.
Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, Harper HA, Robinson AS, Engelhardt JF, Brooks SV, Chamberlain JS. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med. 2002 Mar;8(3):253–261.

Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

March 2002

Volume

8

Issue

3

Start / End Page

253 / 261

Location

United States

Related Subject Headings

  • Protein Conformation
  • Muscular Dystrophy, Duchenne
  • Muscle, Skeletal
  • Mice, Transgenic
  • Mice, Inbred mdx
  • Mice
  • Male
  • Immunology
  • Immunohistochemistry
  • Humans