TY - JOUR
T1 - Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy
AU - Long, Chengzu
AU - Amoasii, Leonela
AU - Mireault, Alex A.
AU - McAnally, John R.
AU - Li, Hui
AU - Sanchez-Ortiz, Efrain
AU - Bhattacharyya, Samadrita
AU - Shelton, John M.
AU - Bassel-Duby, Rhonda
AU - Olson, Eric N.
PY - 2016/1/22
Y1 - 2016/1/22
N2 - 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 correctDMDby skippingmutant dystrophin exons in postnatalmuscle 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 thesemethods 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 potentialmeans of correctingmutations responsible for DMD and other monogenic disorders after birth.
AB - 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 correctDMDby skippingmutant dystrophin exons in postnatalmuscle 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 thesemethods 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 potentialmeans of correctingmutations responsible for DMD and other monogenic disorders after birth.
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U2 - 10.1126/science.aad5725
DO - 10.1126/science.aad5725
M3 - Article
C2 - 26721683
AN - SCOPUS:84961291537
SN - 0036-8075
VL - 351
SP - 400
EP - 403
JO - Science
JF - Science
IS - 6271
ER -