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Your search keyword '"Association Institut de Myologie [Paris]"' showing total 2 results
Start Over Author "Association Institut de Myologie [Paris]" Topic [sdv.bbm.bm]life sciences [q-bio]/biochemistry, molecular biology/molecular biology
2 results on '"Association Institut de Myologie [Paris]"'

1. FISH protocol for Myotonic Dystrophy type 1 cells

Author

Klein, Arnaud F., Arandel, Ludovic, Marie, Joëlle, Furling, Denis, Furling, Denis, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Association Institut de Myologie [Paris], and Centre de Recherche en Myologie

Subjects
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019
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2. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice

Author

Miguel A. Varela, Naira Naouar, David Seoane, Arnaud F. Klein, A Arzumanov, Jack Puymirat, Ashling Holland, Denis Furling, Michael J. Gait, Geneviève Gourdon, Matthew J.A. Wood, Guillaume Bassez, Arnaud Ferry, Lucile Revillod, Ludovic Arandel, Dominic Jauvin, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Généthon, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Association Institut de Myologie [Paris], University of Oxford [Oxford], Université Sorbonne Paris Cité (USPC), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Medical Research Council Laboratory of Molecular Biology, Cambridge, Centre de Recherche en Myologie, Gourdon, Geneviève, University of Oxford, Centre de référence des maladies rares neuromusculaires [CHU Pitié-Salpétriêre], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), SLAC National Accelerator Laboratory (SLAC), and Stanford University

Subjects
0301 basic medicine, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Morpholino, Myotonic dystrophy, 03 medical and health sciences, Splicing factor, chemistry.chemical_compound, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Myocyte, MBNL1, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, RNA, Skeletal muscle, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, RNA splicing, Cancer research, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Antisense oligonucleotides (ASOs) targeting pathologic RNAs have shown promising therapeutic corrections for many genetic diseases including myotonic dystrophy (DM1). Thus, ASO strategies for DM1 can abolish the toxic RNA gain-of-function mechanism caused by nucleus-retained mutant DMPK (DM1 protein kinase) transcripts containing CUG expansions (CUGexps). However, systemic use of ASOs for this muscular disease remains challenging due to poor drug distribution to skeletal muscle. To overcome this limitation, we test an arginine-rich Pip6a cell-penetrating peptide and show that Pip6a-conjugated morpholino phosphorodiamidate oligomer (PMO) dramatically enhanced ASO delivery into striated muscles of DM1 mice following systemic administration in comparison with unconjugated PMO and other ASO strategies. Thus, low-dose treatment with Pip6a-PMO-CAG targeting pathologic expansions is sufficient to reverse both splicing defects and myotonia in DM1 mice and normalizes the overall disease transcriptome. Moreover, treated DM1 patient-derived muscle cells showed that Pip6a-PMO-CAG specifically targets mutant CUGexp-DMPK transcripts to abrogate the detrimental sequestration of MBNL1 splicing factor by nuclear RNA foci and consequently MBNL1 functional loss, responsible for splicing defects and muscle dysfunction. Our results demonstrate that Pip6a-PMO-CAG induces long-lasting correction with high efficacy of DM1-associated phenotypes at both molecular and functional levels, and strongly support the use of advanced peptide conjugates for systemic corrective therapy in DM1.

Published
2019
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