Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice.

Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice. Research Abstract Details 

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Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice. Abstract Text:

Haifang Yin,Qilong Lu,Matthew Wood,

Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, arising from mutations in the dystrophin gene that preclude the synthesis of functional protein. Antisense oligonucleotides (AOs) have been shown to induce specific exon skipping and thereby restore the reading frame and expression of functional dystrophin. In this report, we examine the effects of peptide nucleic acid (PNA) oligonucleotides and PNAs conjugated with peptides including TAT, muscle-specific peptide (MSP), adeno-associated virus 6 (AAV6) functional domain (AAV6), and AAV8 functional domain (AAV8), on exon skipping in vitro and in vivo. Efficient skipping of targeted exon 23 was achieved in cultured mdx myoblasts with PNA and PNA-peptide conjugates. Furthermore, single intramuscular injections of PNA and all PNA-peptide conjugates resulted in significant numbers of dystrophin-positive fibers in the injected tibialis anterior (TA) muscles of mdx mice, with no apparent local toxicity. Similar effects of exon skipping and dystrophin expression were obtained in mice of all ages. PNA and PNA-AAV6, PNA-AAV8 conjugates induced dystrophin expression in a dose-dependent manner. Our results demonstrate that PNAs have a higher efficiency of exon skipping than 2'O methyl phosphorothioate AOs do, and have a potential use in AO chemistry for antisense therapy of DMD.Molecular Therapy (2007) 16 1, 38-45. doi:10.1038/sj.mt.6300329.

Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice. Publishing Authors By Initials

H Yin,Q Lu,M Wood,

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Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular therapy : the journal of the American So

VOLUME: 16

Page Numbers: 38-45

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 30

MONTH: 10

YEAR: 2007

Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice. Information

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LANGUAGE: eng

NlmUniqueID: 100890581

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AFFILIATION: 1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.

Country: United States

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MEDLINETA: Mol Ther

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