TY - JOUR
T1 - Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model
AU - Denti, Michela Alessandra
AU - Rosa, Alessandro
AU - D'Antona, Giuseppe
AU - Sthandier, Olga
AU - De Angelis, Fernanda Gabriella
AU - Nicoletti, Carmine
AU - Allocca, Mariacarmela
AU - Pansarasa, Orietta
AU - Parente, Valeria
AU - Musarò, Antonio
AU - Auricchio, Alberto
AU - Bottinelli, Roberto
AU - Bozzoni, Irene
PY - 2006/3/7
Y1 - 2006/3/7
N2 - Duchenne muscular dystrophy is an X-linked muscle disease characterized by mutations in the dystrophin gene. Many of these can be corrected at the posttranscriptional level by skipping the mutated exon. We have obtained persistent exon skipping in mdx mice by tail vein injection with an adeno-associated viral (AAV) vector expressing antisense sequences as part of the stable cellular U1 small nuclear RNA. Systemic delivery of the AAV construct resulted in effective body-wide colonization, significant recovery of the functional properties in vivo, and lower creatine kinase serum levels, suggesting an overall decrease in muscle wasting. The transduced muscles rescued dystrophin expression and displayed a significant recovery of function toward the normal values at single muscle fiber level. This approach provides solid bases for a systemic use of AAV-mediated antisense-U1 small nuclear RNA expression for the therapeutic treatment of Duchenne muscular dystrophy.
AB - Duchenne muscular dystrophy is an X-linked muscle disease characterized by mutations in the dystrophin gene. Many of these can be corrected at the posttranscriptional level by skipping the mutated exon. We have obtained persistent exon skipping in mdx mice by tail vein injection with an adeno-associated viral (AAV) vector expressing antisense sequences as part of the stable cellular U1 small nuclear RNA. Systemic delivery of the AAV construct resulted in effective body-wide colonization, significant recovery of the functional properties in vivo, and lower creatine kinase serum levels, suggesting an overall decrease in muscle wasting. The transduced muscles rescued dystrophin expression and displayed a significant recovery of function toward the normal values at single muscle fiber level. This approach provides solid bases for a systemic use of AAV-mediated antisense-U1 small nuclear RNA expression for the therapeutic treatment of Duchenne muscular dystrophy.
KW - Adeno-associated virus vectors
KW - Antisense
KW - Dystrophin
KW - Exon skipping
KW - Small nuclear RNA
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U2 - 10.1073/pnas.0508917103
DO - 10.1073/pnas.0508917103
M3 - Article
C2 - 16501048
AN - SCOPUS:33644857020
VL - 103
SP - 3758
EP - 3763
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 10
ER -