scholarly journals Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy

Science ◽  
2015 ◽  
Vol 351 (6271) ◽  
pp. 400-403 ◽  
Author(s):  
C. Long ◽  
L. Amoasii ◽  
A. A. Mireault ◽  
J. R. McAnally ◽  
H. Li ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Genome Editing ◽  
Dystrophin Expression

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 Reading Frame Correction by Targeted Genome Editing Restores Dystrophin Expression in Cells From Duchenne Muscular Dystrophy Patients

2013 ◽  
Vol 21 (9) ◽  
pp. 1718-1726 ◽  
Author(s):  
David G Ousterout ◽  
Pablo Perez-Pinera ◽  
Pratiksha I Thakore ◽  
Ami M Kabadi ◽  
Matthew T Brown ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Genome Editing ◽  
Reading Frame ◽  
Dystrophin Expression ◽  
In Cells

Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin expression in a mouse model of muscular dystrophy

Biomaterials ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 1478-1486 ◽  
Author(s):  
Hee Seok Yang ◽  
Nicholas Ieronimakis ◽  
Jonathan H. Tsui ◽  
Hong Nam Kim ◽  
Kahp-Yang Suh ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Muscle Cell ◽  
Dystrophin Expression

scholarly journals CRISPR/Cas9 editing of directly reprogrammed myogenic progenitors restores dystrophin expression in a mouse model of muscular dystrophy

2022 ◽  
Author(s):  
Seraina A. Domenig ◽  
Nicola Bundschuh ◽  
Ajda Lenardič ◽  
Adhideb Ghosh ◽  
Inseon Kim ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Dystrophin Expression

scholarly journals In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy

Science ◽  
2015 ◽  
Vol 351 (6271) ◽  
pp. 403-407 ◽  
Author(s):  
C. E. Nelson ◽  
C. H. Hakim ◽  
D. G. Ousterout ◽  
P. I. Thakore ◽  
E. A. Moreb ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Genome Editing ◽  
Muscle Function
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