PMID- 11095710
OWN - NLM
STAT- MEDLINE
DCOM- 20010118
LR  - 20220309
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 97
IP  - 25
DP  - 2000 Dec 5
TI  - Adeno-associated virus vector carrying human minidystrophin genes effectively 
      ameliorates muscular dystrophy in mdx mouse model.
PG  - 13714-9
AB  - Duchenne muscular dystrophy (DMD) is the most common and lethal genetic muscle 
      disorder, caused by recessive mutations in the dystrophin gene. One of every 
      3,500 males suffers from DMD, yet no treatment is currently available. Genetic 
      therapeutic approaches, using primarily myoblast transplantation and 
      adenovirus-mediated gene transfer, have met with limited success. 
      Adeno-associated virus (AAV) vectors, although proven superior for muscle gene 
      transfer, are too small (5 kb) to package the 14-kb dystrophin cDNA. Here we have 
      created a series of minidystrophin genes (<4.2 kb) under the control of a 
      muscle-specific promoter that readily package into AAV vectors. When injected 
      into the muscle of mdx mice (a DMD model), two of the minigenes resulted in 
      efficient and stable expression in a majority of the myofibers, restoring the 
      missing dystrophin and dystrophin-associated protein complexes onto the plasma 
      membrane. More importantly, this AAV treatment ameliorated dystrophic pathology 
      in mdx muscle and led to normal myofiber morphology, histology, and cell membrane 
      integrity. Thus, we have defined minimal functional dystrophin units and 
      demonstrated the effectiveness of using AAV to deliver the minigenes in vivo, 
      offering a promising avenue for DMD gene therapy.
FAU - Wang, B
AU  - Wang B
AD  - Department of Molecular Genetics and Biochemistry, Gene Therapy Center, and 
      Duchenne Muscular Dystrophy Research Center and Department of Orthopedic Surgery, 
      University of Pittsburgh, Pittsburgh, PA 15261, USA.
FAU - Li, J
AU  - Li J
FAU - Xiao, X
AU  - Xiao X
LA  - eng
GR  - P01 AR045925/AR/NIAMS NIH HHS/United States
GR  - R01 AR045967/AR/NIAMS NIH HHS/United States
GR  - AR 45926/AR/NIAMS NIH HHS/United States
GR  - AR45967/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Dystrophin)
SB  - IM
CIN - Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13464-6. PMID: 11095702
MH  - Animals
MH  - Dependovirus/*genetics
MH  - Disease Models, Animal
MH  - Dystrophin/*genetics
MH  - *Genetic Vectors
MH  - Humans
MH  - Mice
MH  - Mice, Inbred mdx
MH  - Muscular Dystrophy, Duchenne/*genetics/pathology
PMC - PMC17641
EDAT- 2000/11/30 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/06/05
CRDT- 2000/11/30 11:00
PHST- 2000/11/30 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/30 11:00 [entrez]
PHST- 2001/06/05 00:00 [pmc-release]
AID - 240335297 [pii]
AID - 3352 [pii]
AID - 10.1073/pnas.240335297 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9. doi: 10.1073/pnas.240335297.