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


ABSTRACT: CRISPR/Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene. To correct DMD by skipping mutant dystrophin exons in postnatal muscle tissue in vivo, we used adeno-associated virus-9 (AAV9) to deliver gene-editing components to postnatal mdx mice, a model of DMD. Different modes of AAV9 delivery were systematically tested, including intraperitoneal at postnatal day 1 (P1), intramuscular at P12, and retro-orbital at P18. Each of these methods restored dystrophin protein expression in cardiac and skeletal muscle to varying degrees, and expression increased from 3 to 12 weeks after injection. Postnatal gene editing also enhanced skeletal muscle function, as measured by grip strength tests 4 weeks after injection. This method provides a potential means of correcting mutations responsible for DMD and other monogenic disorders after birth.

SUBMITTER: Long C 

PROVIDER: S-EPMC4760628 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Long Chengzu C   Amoasii Leonela L   Mireault Alex A AA   McAnally John R JR   Li Hui H   Sanchez-Ortiz Efrain E   Bhattacharyya Samadrita S   Shelton John M JM   Bassel-Duby Rhonda R   Olson Eric N EN  

Science (New York, N.Y.) 20151231 6271


CRISPR/Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene. To correct DMD by skipping mutant dystrophin exons in postnatal muscle tissue in vivo, we used adeno-associated virus-9 (AAV9) to deliver gene-editing components to postnatal mdx mice, a model of DMD. Different modes of AAV9 delivery were systematically tested, including intraperitoneal at postnatal day 1 (P1),  ...[more]

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