Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function.
Antisense oligonucleotides (AOs) have the potential to induce functional dystrophin protein expression via exon skipping by restoring in-frame transcripts in the majority of patients suffering from Duchenne muscular dystrophy (DMD). AOs of morpholino phosphoroamidate (PMO) and 2'-O-methyl phosp...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1797105575346044928 |
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| author | Yin, H Moulton, H Seow, Y Boyd, C Boutilier, J Iverson, P Wood, M |
| author_facet | Yin, H Moulton, H Seow, Y Boyd, C Boutilier, J Iverson, P Wood, M |
| author_sort | Yin, H |
| collection | OXFORD |
| description | Antisense oligonucleotides (AOs) have the potential to induce functional dystrophin protein expression via exon skipping by restoring in-frame transcripts in the majority of patients suffering from Duchenne muscular dystrophy (DMD). AOs of morpholino phosphoroamidate (PMO) and 2'-O-methyl phosphorothioate RNA (2'Ome RNA) chemistry have been shown to restore dystrophin expression in skeletal muscle but not in heart, following high-dose systemic delivery in murine models of muscular dystrophy (mdx). Exploiting the cell transduction properties of two basic arginine-rich cell penetrating peptides, we demonstrate widespread systemic correction of dystrophin expression in body-wide muscles and cardiac tissue in adult dystrophic mdx mice, with a single low-dose injection of peptide-conjugated PMO AO. This approach was sufficient to restore uniform, high-level dystrophin protein expression in peripheral muscle and cardiac tissue, with robust sarcolemmal relocalization of the dystrophin-associated protein complex and functional improvement in muscle. Peptide-conjugated AOs therefore have significant potential for systemic correction of the DMD phenotype. |
| first_indexed | 2024-03-07T06:49:21Z |
| format | Journal article |
| id | oxford-uuid:fbff0486-8c70-48bc-8c95-297e57d9ba35 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:49:21Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:fbff0486-8c70-48bc-8c95-297e57d9ba352022-03-27T13:17:42ZCell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fbff0486-8c70-48bc-8c95-297e57d9ba35EnglishSymplectic Elements at Oxford2008Yin, HMoulton, HSeow, YBoyd, CBoutilier, JIverson, PWood, MAntisense oligonucleotides (AOs) have the potential to induce functional dystrophin protein expression via exon skipping by restoring in-frame transcripts in the majority of patients suffering from Duchenne muscular dystrophy (DMD). AOs of morpholino phosphoroamidate (PMO) and 2'-O-methyl phosphorothioate RNA (2'Ome RNA) chemistry have been shown to restore dystrophin expression in skeletal muscle but not in heart, following high-dose systemic delivery in murine models of muscular dystrophy (mdx). Exploiting the cell transduction properties of two basic arginine-rich cell penetrating peptides, we demonstrate widespread systemic correction of dystrophin expression in body-wide muscles and cardiac tissue in adult dystrophic mdx mice, with a single low-dose injection of peptide-conjugated PMO AO. This approach was sufficient to restore uniform, high-level dystrophin protein expression in peripheral muscle and cardiac tissue, with robust sarcolemmal relocalization of the dystrophin-associated protein complex and functional improvement in muscle. Peptide-conjugated AOs therefore have significant potential for systemic correction of the DMD phenotype. |
| spellingShingle | Yin, H Moulton, H Seow, Y Boyd, C Boutilier, J Iverson, P Wood, M Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. |
| title | Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. |
| title_full | Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. |
| title_fullStr | Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. |
| title_full_unstemmed | Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. |
| title_short | Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. |
| title_sort | cell penetrating peptide conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function |
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