Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

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Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chim...

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Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdx mouse muscle.

The mdx mouse model of muscular dystrophy arose due to a nonsense mutation in exon 23 of the dystrophin gene. We have previously demonstrated that 2'-O-methyl phosphorothioate antisense oligonucleotides (AOs) can induce removal of exon 23 during processing of the primary transcript. This results in an in-frame mRNA transcript and subsequent expression of a slightly shorter dystrophin protein in...

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Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion.

Deletion and duplication of one or more exons in the dystrophin gene account for 70% of patients with Duchenne and Becker muscular dystrophies (DMD and BMD) and other allelic clinical entities such as raised serum creatine kinase and X linked dilated cardiomyopathy (XLDC). The severity of the resulting phenotype can be generally predicted by whether these mutations lead to translation frame dis...

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ONLINE MUTATION REPORT Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion

Deletion and duplication of one or more exons in the dystrophin gene account for 70% of patients with Duchenne and Becker muscular dystrophies (DMD and BMD) and other allelic clinical entities such as raised serum creatine kinase and X linked dilated cardiomyopathy (XLDC). The severity of the resulting phenotype can be generally predicted by whether these mutations lead to translation frame dis...

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Multiple exon skipping strategies to by-pass dystrophin mutations

Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy. Dystrophin mutations will require the removal of one or more exons to restore the reading frame and in some cases, multiple exon skipping strategies exist to restore dystrophin expression. However, for some small intra-exonic ...

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ژورنال

عنوان ژورنال: Molecular Therapy - Nucleic Acids

سال: 2020

ISSN: 2162-2531

DOI: 10.1016/j.omtn.2020.08.026