In vivo delivery of naked antisense oligos in aged mdx mice: Analysis of dystrophin restoration in skeletal and cardiac muscle

被引：26

作者：

Vitiello, Libero ^{[1
]}

Bassi, Nicola ^{[1
]}

Campagnolo, Paola ^{[1
]}

Zaccariotto, Eva ^{[1
]}

Occhi, Gianluca ^{[1
]}

Malerba, Alberto ^{[1
]}

Pigozzo, Sarah ^{[1
]}

Reggiani, Carlo ^{[2
]}

Ausoni, Simonetta ^{[3
]}

Zagila, Tania ^{[3
]}

Gamba, Piergiorgio ^{[4
]}

Baroni, Maurizio D. ^{[1
]}

Ditadi, Andrea P. ^{[4
]}

机构：

[1] Univ Padua, Dept Biol, I-35121 Padua, Italy

[2] Univ Padua, Dept Anat & Physiol, Padua, Italy

[3] Univ Padua, Dept Biomed Sci, Padua, Italy

[4] Univ Padua, Dept Pediat & Pediat Surg, Padua, Italy

来源：

NEUROMUSCULAR DISORDERS | 2008年 / 18卷 / 08期

关键词：

exon skipping; antisense oligonucleotides; mdx mouse; force measurement; cardiac muscle;

D O I：

10.1016/j.nmd.2008.05.011

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Antisense-mediated exon skipping holds great potential for the treatment of DMD. In mdx mice, functional recovery of skeletal muscle has been obtained upon systemic delivery of "naked" oligonucleotides or viral vectors encoding for antisense snRNAs. However, amongst the studies reported so far, which used either neonatal or Young adult animals - only one achieved dystrophin restoration in cardiac Muscle. Using all adeno-associated vector. Here we report the in vivo delivery of morpholino oligos in aged mdx mice. both ill skeletal muscle. via intra-arterial injection, and ill Cardiac muscle, via intra-musclar injection. Localized intra-arterial delivery yielded high levels of dystrophin restoration and just two doses of 100 mu g each resulted into detectable force recovery ill the EDL muscles of treated limbs. On the other hand, upon intra-cardiac injections in the left ventricle wall the skipping effect was much lower than what obtained in tibialis anterior muscles injected with comparable amounts of oligos. This latter finding Suggests that even upon direct delivery antisense-mediated dystrophin restoration in cardiac muscle might suffer from limitations that do not exist in skeletal muscle. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：597 / 605

页数：9

共 24 条

[1] Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense [J].