Immortalized Canine Dystrophic Myoblast Cell Lines for Development of Peptide-Conjugated Splice-Switching Oligonucleotides
| العنوان: | Immortalized Canine Dystrophic Myoblast Cell Lines for Development of Peptide-Conjugated Splice-Switching Oligonucleotides |
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| المؤلفون: | Yoshitsugu Aoki, A Arzumanov, Kamel Mamchaoui, Tone Yuichiro, Rika Maruyama, Graham McClorey, Shin'ichi Takeda, Toshifumi Yokota, Yasumasa Hashimoto, Maria K. Tsoumpra, Michihiro Imamura, Vincent Mouly, Michael J. Gait, Matthew J.A. Wood, Reiko Terada |
| المساهمون: | Gestionnaire, HAL Sorbonne Université 5, Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Alberta, University of Oxford, UMRS974, Université Pierre et Marie Curie - Paris 6 (UPMC), University of Oxford [Oxford], Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de Recherche en Myologie |
| المصدر: | Nucleic Acid Therapeutics Nucleic Acid Therapeutics, 2021, 31 (2), pp.172-181. ⟨10.1089/nat.2020.0907⟩ Nucleic Acid Therapeutics, Mary Ann Liebert, Inc. publishers, 2021, 31 (2), pp.172-181. ⟨10.1089/nat.2020.0907⟩ |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, canine X-linked muscular dystrophy in Japan (CXMD J ), Duchenne muscular dystrophy, Biochemistry, Morpholinos, Dystrophin, Myoblasts, Mice, 0302 clinical medicine, Drug Discovery, Muscular dystrophy, Telomerase, ComputingMilieux_MISCELLANEOUS, biology, Chemistry, Myogenesis, phosphorodiamidate morpholino oligomer, Exons, Original Papers, 3. Good health, Cell biology, 030220 oncology & carcinogenesis, Molecular Medicine, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], splice-switching oligonucleotides, Nonsense mutation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Line, 03 medical and health sciences, Dogs, Genetics, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Telomerase reverse transcriptase, Molecular Biology, Cyclin-Dependent Kinase 4, Genetic Therapy, immortalized dystrophic canine myoblast, Oligonucleotides, Antisense, canine X-linked muscular dystrophy in Japan (CXMDJ), medicine.disease, Exon skipping, Muscular Dystrophy, Duchenne, 030104 developmental biology, biology.protein, Cell-penetrating peptide, RNA Splice Sites, Peptides, cell-penetrating peptide |
| الوصف: | Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease caused by frameshift or nonsense mutations in the DMD gene, resulting in the loss of dystrophin from muscle membranes. Exon skipping using splice-switching oligonucleotides (SSOs) restores the reading frame of DMD pre-mRNA by generating internally truncated but functional dystrophin protein. To potentiate effective tissue-specific targeting by functional SSOs, it is essential to perform accelerated and reliable in vitro screening-based assessment of novel oligonucleotides and drug delivery technologies, such as cell-penetrating peptides, before their in vivo pharmacokinetic and toxicity evaluation. We have established novel canine immortalized myoblast lines by transducing murine cyclin-dependent kinase-4 and human telomerase reverse transcriptase genes into myoblasts isolated from beagle-based wild-type or canine X-linked muscular dystrophy in Japan (CXMDJ) dogs. These myoblast lines exhibited improved myogenic differentiation and increased proliferation rates compared with passage-15 primary parental myoblasts, and their potential to differentiate into myotubes was maintained in later passages. Using these dystrophin-deficient immortalized myoblast lines, we demonstrate that a novel cell-penetrating peptide (Pip8b2)-conjugated SSO markedly improved multiexon skipping activity compared with the respective naked phosphorodiamidate morpholino oligomers. In vitro screening using immortalized canine cell lines will provide a basis for further pharmacological studies on drug delivery tools. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2159-3337 2159-3345 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37e6bb92dfaba5985c0590e408a2e368 https://hal.sorbonne-universite.fr/hal-03276095 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....37e6bb92dfaba5985c0590e408a2e368 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21593337 21593345 |
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