Evaluating the Impact of Variable Phosphorothioate Content in Tricyclo-DNA Antisense Oligonucleotides in a Duchenne Muscular Dystrophy Mouse Model

2019 ◽  
Vol 29 (3) ◽  
pp. 148-160 ◽  
Author(s):  
Lucía Echevarría ◽  
Philippine Aupy ◽  
Karima Relizani ◽  
Thomas Bestetti ◽  
Graziella Griffith ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Antisense Oligonucleotides ◽  
The Impact

Feasibility of SPECT-CT Imaging to Study the Pharmacokinetics of Antisense Oligonucleotides in a Mouse Model of Duchenne Muscular Dystrophy

2017 ◽  
Vol 27 (4) ◽  
pp. 221-231 ◽  
Author(s):  
Evita van de Steeg ◽  
Tilman Läppchen ◽  
Begoña Aguilera ◽  
Harm T. Jansen ◽  
Daan Muilwijk ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Antisense Oligonucleotides ◽  
Ct Imaging

scholarly journals A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy

2020 ◽  
Vol 13 (9) ◽  
pp. dmm045369
Author(s):  
Tatianna Wai Ying Wong ◽  
Abdalla Ahmed ◽  
Grace Yang ◽  
Eleonora Maino ◽  
Sydney Steiman ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Early Onset ◽  
Treatment Strategies ◽  
Clinical Model ◽  
Life Threatening ◽  
Cardiac Muscles ◽  
Almost All ◽  
The Impact

ABSTRACTDuchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. Although there has been extensive effort in creating animal models to study treatment strategies for DMD, most fail to recapitulate the complete skeletal and cardiac disease manifestations that are presented in affected patients. Here, we generated a mouse model mirroring a patient deletion mutation of exons 52-54 (Dmd Δ52-54). The Dmd Δ52-54 mutation led to the absence of dystrophin, resulting in progressive muscle deterioration with weakened muscle strength. Moreover, Dmd Δ52-54 mice present with early-onset hypertrophic cardiomyopathy, which is absent in current pre-clinical dystrophin-deficient mouse models. Therefore, Dmd Δ52-54 presents itself as an excellent pre-clinical model to evaluate the impact on skeletal and cardiac muscles for both mutation-dependent and -independent approaches.

scholarly journals Cyclic Peptides to Improve Delivery and Exon Skipping of Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy

2018 ◽  
Vol 26 (1) ◽  
pp. 132-147 ◽  
Author(s):  
Silvana M.G. Jirka ◽  
Peter A.C. ’t Hoen ◽  
Valeriano Diaz Parillas ◽  
Christa L. Tanganyika-de Winter ◽  
Ruurd C. Verheul ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Antisense Oligonucleotides ◽  
Cyclic Peptides ◽  
Exon Skipping

scholarly journals Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model

2017 ◽  
Vol 8 ◽  
pp. 144-157 ◽  
Author(s):  
Karima Relizani ◽  
Graziella Griffith ◽  
Lucía Echevarría ◽  
Faouzi Zarrouki ◽  
Patricia Facchinetti ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Safety Profile ◽  
Antisense Oligonucleotides ◽  
Efficacy And Safety

scholarly journals In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Menglong Chen ◽  
Hui Shi ◽  
Shixue Gou ◽  
Xiaomin Wang ◽  
Lei Li ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Genome Editing ◽  
Large Scale ◽  
Gene Editing ◽  
High Efficiency ◽  
Muscle Fibers ◽  
Muscle Cells

Abstract Background Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

scholarly journals Functional and Molecular Effects of Arginine Butyrate and Prednisone on Muscle and Heart in the mdx Mouse Model of Duchenne Muscular Dystrophy

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e11220 ◽  
Author(s):  
Alfredo D. Guerron ◽  
Rashmi Rawat ◽  
Arpana Sali ◽  
Christopher F. Spurney ◽  
Emidio Pistilli ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Mdx Mouse ◽  
Molecular Effects ◽  
Arginine Butyrate
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