The myotonic dystrophies: molecular, clinical, and therapeutic challenges, Lancet Neurol, vol.11, pp.891-905, 2012. ,
Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy, Nature, vol.355, pp.547-548, 1992. ,
Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3? end of a transcript encoding a protein kinase family member, Cell, vol.68, pp.799-808, 1992. ,
Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy, Nature, vol.355, pp.545-546, 1992. ,
, , 1992.
, Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene, Science, vol.255, pp.1253-1255
Cloning of the essential myotonic dystrophy region and mapping of the putative defect, Nature, vol.355, pp.548-551, 1992. ,
Myotonic dystrophy protein kinase (DMPK) and its role in the pathogenesis of myotonic dystrophy 1, Cell Signal, vol.20, pp.1935-1941, 2008. ,
An unstable triplet repeat in a gene related to myotonic muscular dystrophy, Science, vol.255, pp.1256-1258, 1992. ,
Intergenerational instability of the expanded CTG repeat in the DMPK gene: studies in human gametes and preimplantation embryos, Am. J. Hum. Genet, vol.75, pp.325-329, 2004. ,
Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity, Hum. Mol. Genet, vol.21, pp.3558-3567, 2012. ,
Myotonic dystrophy mouse models: towards rational therapy development, Trends Mol. Med, vol.17, pp.506-517, 2011. ,
Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues, J. Cell Biol, vol.128, pp.995-1002, 1995. ,
In vivo co-localisation of MBNL protein with DMPK expanded-repeat transcripts, Nucleic Acids Res, vol.29, pp.2766-2771, 2001. ,
Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy, Science, vol.280, pp.737-741, 1998. ,
Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy, Nat. Genet, vol.29, pp.40-47, 2001. ,
A muscleblind knockout model for myotonic dystrophy, Science, vol.302, 1978. ,
Muscleblind proteins regulate alternative splicing, EMBO J, vol.23, pp.3103-3112, 2004. ,
Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy, Hum. Mol. Genet, vol.15, pp.2087-2097, 2006. ,
MBNL proteins repress ES-cell-specific alternative splicing and reprogramming, Nature, vol.498, pp.241-245, 2013. ,
Splicing biomarkers of disease severity in myotonic dystrophy, Ann. Neurol, vol.74, pp.862-872, 2013. ,
, Therapeutic Approaches for Dominant Muscle Diseases: Highlight on Myotonic Dystrophy. Curr, vol.15, pp.329-337, 2015.
Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions, Gene Ther, vol.10, pp.795-802, 2003. ,
Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs, Nat. Struct. Mol. Biol, vol.18, pp.85-87, 2011. ,
Targeting nuclear RNA for in vivo correction of myotonic dystrophy, Nature, vol.488, pp.111-115, 2012. ,
Treatment of type 1 myotonic dystrophy by engineering site-specific RNA endonucleases that target (CUG)(n) repeats, Mol. Ther, vol.22, pp.312-320, 2014. ,
Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9, Cell, vol.170, pp.899-912, 2017. ,
Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy, Proc. Natl. Acad. Sci. U S A, vol.103, pp.11748-11753, 2006. ,
Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA, Science, vol.325, pp.336-339, 2009. ,
, , 2009.
, Pentamidine reverses the splicing defects associated with myotonic dystrophy, Proc. Natl. Acad. Sci. U S A, vol.106, pp.18551-18556
In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models, Proc. Natl. Acad. Sci. U S A, vol.108, pp.11866-11871, 2011. ,
A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity, Science, vol.337, pp.816-821, 2012. ,
Refining strategies to translate genome editing to the clinic, Nat. Med, vol.23, pp.415-423, 2017. ,
RNA-guided human genome engineering via Cas9, Science, vol.339, pp.823-826, 2013. ,
, , 2016.
, Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy, Science, vol.351, pp.400-403
In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy, Science, vol.351, pp.403-407, 2016. ,
In vivo gene editing in dystrophic mouse muscle and muscle stem cells, Science, vol.351, pp.407-411, 2016. ,
Genome engineering: a new approach to gene therapy for neuromuscular disorders, Nat. Rev. Neurol, vol.13, pp.647-661, 2017. ,
SaCas9 Requires 5'-NNGRRT-3' PAM for Sufficient Cleavage and Possesses Higher Cleavage Activity than SpCas9 or FnCpf1 in Human Cells, Biotechnol. J, vol.13, p.1700561, 2018. ,
, , 1997.
, Moderate intergenerational and somatic instability of a 55-CTG repeat in transgenic mice, Nat. Genet, vol.15, pp.190-192
CTG trinucleotide repeat "big jumps": large expansions, small mice, PLoS Genet, p.52, 2007. ,
Processing-independent CRISPR RNAs limit natural transformation in Neisseria meningitidis, Mol. Cell, vol.50, pp.488-503, 2013. ,
Genome editing for nucleotide repeat disorders: towards a new therapeutic approach for Myotonic Dystrophy type 1, Mol. Ther, vol.24, pp.129-130, 2016. ,
In vivo genome editing using Staphylococcus aureus Cas9, Nature, vol.520, pp.186-191, 2015. ,
Easy quantitative assessment of genome editing by sequence trace decomposition, Nucleic Acids Res, vol.42, p.168, 2014. ,
Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds, Dis. Model. Mech, vol.10, pp.487-497, 2017. ,
URL : https://hal.archives-ouvertes.fr/hal-01519721
Origin of the expansion mutation in myotonic dystrophy, Nat. Genet, vol.4, pp.72-76, 1993. ,
, , 2012.
, Molecular, physiological, and motor performance defects in DMSXL mice carrying >1,000 CTG repeats from the human DM1 locus, PLoS Genet, vol.8, p.1003043
AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis, Hum. Mol. Genet, vol.17, pp.2132-2143, 2008. ,
URL : https://hal.archives-ouvertes.fr/inserm-00311078
Chromatin accessibility and guide sequence secondary structure affect CRISPR-Cas9 gene editing efficiency, FEBS Lett, vol.591, pp.1892-1901, 2017. ,
CRISPR/Cas9-Induced (CTGCAG)n Repeat Instability in the Myotonic Dystrophy Type 1 Locus: Implications for Therapeutic Genome Editing, Mol. Ther, vol.25, pp.24-43, 2017. ,
, , 2017.
Mediated Deletion of CTG Expansions Recovers Normal Phenotype in Myogenic Cells Derived from Myotonic Dystrophy 1 Patients, Mol. Ther. Nucleic Acids, vol.9, pp.337-348 ,
Efficient CRISPR/Cas9-mediated editing of trinucleotide repeat expansion in myotonic dystrophy patientderived iPS and myogenic cells, Nucleic Acids Res, vol.46, pp.8275-8298, 2018. ,
Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy, Mol. Ther, vol.24, pp.1378-1387, 2016. ,
Shortening trinucleotide repeats using highly specific endonucleases: a possible approach to gene therapy?, Trends Genet, vol.31, pp.177-186, 2015. ,
URL : https://hal.archives-ouvertes.fr/pasteur-01370705
TALEN-Induced Double-Strand Break Repair of CTG Trinucleotide Repeats, Cell Rep, vol.22, pp.2146-2159, 2018. ,
URL : https://hal.archives-ouvertes.fr/hal-01727334
Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase, Nat. Commun, vol.7, p.13272, 2016. ,
Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9, Mol. Cell, vol.68, pp.479-490, 2017. ,
Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy, Nat. Commun, vol.8, p.14454, 2017. ,
Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy, 2018. ,
, , 2015.
, Liver-directed lentiviral gene therapy in a dog model of hemophilia B, Sci. Transl. Med, vol.7, pp.277-228
Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences, Nat. Biotechnol, vol.17, pp.241-245, 1999. ,
Intravenous Administration of a MTMR2-Encoding AAV Vector Ameliorates the Phenotype of Myotubular Myopathy in Mice, J. Neuropathol. Exp. Neurol, vol.77, pp.282-295, 2018. ,
Transgenic mice carrying large human genomic sequences with expanded CTG repeat mimic closely the DM CTG repeat intergenerational and somatic instability, Hum. Mol. Genet, vol.9, pp.1185-1194, 2000. ,
Localization of trinucleotide repeat sequences in Myotonic Distrophy cells using a single fluorochrome-labeled PNA probe, BioTechniques, vol.24, pp.472-476, 1998. ,
Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities, Hum. Mol. Genet, vol.10, pp.2717-2726, 2001. ,
URL : https://hal.archives-ouvertes.fr/hal-00179658
PEAR: a fast and accurate Illumina Paired-End reAd mergeR, Bioinformatics, vol.30, pp.614-620, 2014. ,
Cutadapt removes adapter sequences from high-throughput sequencing reads, EMBnet.journal, vol.17, p.10, 2011. ,
CRISPResso2 provides accurate and rapid genome editing sequence analysis, Nat. Biotechnol, vol.37, pp.224-226, 2019. ,
, Genomic DNA from non-transduced cells (NT) and cells transduced with only one lentiviral vector (SaCas9 or sgRNA, MOI 50) was used as controls. (C) Percentage of DMPK CTG repeats independent biological replicates ± SD. Statistical analysis by two-tailed Student ttest
, DM1 myoblast clones were isolated from the bulk population after transduction with lentiviral vectors; isolated clones were analyzed for the presence of nuclear foci (A) and presence of DMPK CTG repeats (B to F). (A) FISH-IF images of a representative DM1 myoblast clone without foci (DM1-Delta clone 22); DM1 clones nontransduced (DM1) or transduced with MOI 50 of a lentiviral vector expressing SaCas9 (DM1-Cas9) or sgRNA 4-23 only (DM1-sgRNA) were used as control. SaCas9 (?-HA) is shown in red, GFP in green, RNA foci in yellow, Figure 3. Deletion of Expanded CTG Repeats and Foci Disappearance in DM1 Myoblasts Treated with CRISPR-SaCas9
, Statistical analysis with two-tailed Student's t test. ***: P < 0.001. (C) Total number of myonuclei per fiber in TA of wild-type (WT) and homozygous (HMZ) mice 4 weeks after injection of either PBS or rAAV9-SaCas9 + rAAV9-sgRNA 4-23 vectors. Data are represented as means ± SD (N=3 for WT mice; N=10 for HMZ mice), vol.10