Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases
Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle degeneration, caused by the absence of dystrophin. Exon skipping by antisense oligonucleotides (ASOs) has recently gained recognition as therapeutic approach in DMD. Conjugation of a peptide to the phosphor...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2019
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| _version_ | 1797056615870889984 |
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| author | Tsoumpra, MK Fukumoto, S Matsumoto, T Takeda, S Wood, MJA Aoki, Y |
| author_facet | Tsoumpra, MK Fukumoto, S Matsumoto, T Takeda, S Wood, MJA Aoki, Y |
| author_sort | Tsoumpra, MK |
| collection | OXFORD |
| description | Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle degeneration, caused by the absence of dystrophin. Exon skipping by antisense oligonucleotides (ASOs) has recently gained recognition as therapeutic approach in DMD. Conjugation of a peptide to the phosphorodiamidate morpholino backbone (PMO) of ASOs generated the peptide-conjugated PMOs (PPMOs) that exhibit a dramatically improved pharmacokinetic profile. When tested in animal models, PPMOs demonstrate effective exon skipping in target muscles and prolonged duration of dystrophin restoration after a treatment regime. Herein we summarize the main pathophysiological features of DMD and the emergence of PPMOs as promising exon skipping agents aiming to rescue defective gene expression in DMD and other neuromuscular diseases. The listed PPMO laboratory findings correspond to latest trends in the field and highlight the obstacles that must be overcome prior to translating the animal-based research into clinical trials tailored to the needs of patients suffering from neuromuscular diseases. |
| first_indexed | 2024-03-06T19:25:05Z |
| format | Journal article |
| id | oxford-uuid:1b6e0a58-79de-42f9-bfa5-0f3dcf933c22 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:25:05Z |
| publishDate | 2019 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:1b6e0a58-79de-42f9-bfa5-0f3dcf933c222022-03-26T11:00:21ZPeptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseasesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1b6e0a58-79de-42f9-bfa5-0f3dcf933c22EnglishSymplectic ElementsElsevier2019Tsoumpra, MKFukumoto, SMatsumoto, TTakeda, SWood, MJAAoki, YDuchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle degeneration, caused by the absence of dystrophin. Exon skipping by antisense oligonucleotides (ASOs) has recently gained recognition as therapeutic approach in DMD. Conjugation of a peptide to the phosphorodiamidate morpholino backbone (PMO) of ASOs generated the peptide-conjugated PMOs (PPMOs) that exhibit a dramatically improved pharmacokinetic profile. When tested in animal models, PPMOs demonstrate effective exon skipping in target muscles and prolonged duration of dystrophin restoration after a treatment regime. Herein we summarize the main pathophysiological features of DMD and the emergence of PPMOs as promising exon skipping agents aiming to rescue defective gene expression in DMD and other neuromuscular diseases. The listed PPMO laboratory findings correspond to latest trends in the field and highlight the obstacles that must be overcome prior to translating the animal-based research into clinical trials tailored to the needs of patients suffering from neuromuscular diseases. |
| spellingShingle | Tsoumpra, MK Fukumoto, S Matsumoto, T Takeda, S Wood, MJA Aoki, Y Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases |
| title | Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases |
| title_full | Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases |
| title_fullStr | Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases |
| title_full_unstemmed | Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases |
| title_short | Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases |
| title_sort | peptide conjugate antisense based splice correction for duchenne muscular dystrophy and other neuromuscular diseases |
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