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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642283/ https://www.ncbi.nlm.nih.gov/pubmed/31257147 http://dx.doi.org/10.1016/j.ebiom.2019.06.036 |
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author | Tsoumpra, Maria K. Fukumoto, Seiji Matsumoto, Toshio Takeda, Shin'ichi Wood, Matthew J.A. Aoki, Yoshitsugu |
author_facet | Tsoumpra, Maria K. Fukumoto, Seiji Matsumoto, Toshio Takeda, Shin'ichi Wood, Matthew J.A. Aoki, Yoshitsugu |
author_sort | Tsoumpra, Maria K. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6642283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-66422832019-07-29 Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases Tsoumpra, Maria K. Fukumoto, Seiji Matsumoto, Toshio Takeda, Shin'ichi Wood, Matthew J.A. Aoki, Yoshitsugu EBioMedicine Review 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. Elsevier 2019-06-27 /pmc/articles/PMC6642283/ /pubmed/31257147 http://dx.doi.org/10.1016/j.ebiom.2019.06.036 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Review Tsoumpra, Maria K. Fukumoto, Seiji Matsumoto, Toshio Takeda, Shin'ichi Wood, Matthew J.A. Aoki, Yoshitsugu 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 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642283/ https://www.ncbi.nlm.nih.gov/pubmed/31257147 http://dx.doi.org/10.1016/j.ebiom.2019.06.036 |
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