| VMO23 투여 용량에 따른 Ducheen형 근이영양증 생쥐의 Dystrophin 발현과 근기능에 미치는 영향 |
| 최승준 |
| 경성대학교 |
| Dose-Dependent Effects of Exon Skipping by Vivo-Morpholinos 23 on Dystrophin Protein Production and Muscle Function in Dystrophic mdx Mice |
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| ABSTRACT |
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Duchenne muscular dystrophy(DMD) is a severe degenerative muscle disease caused by defects in the dystrophin gene. Steric-block Morpholino antisense oligomers have been shown to induce exon skipping and partially restored Dystrophin function in the skeletal muscles of DMD animal models, particularly in mdx mice. However, Morpholinos-mediated exon skipping in the heart has been only marginal due to inadequate delivery of Morpholinos into the cardiac muscles. In this paper we demonstrated that a Vivo Morpholino oligo(VMO23), a new type of delivery-enhanced Morpholino antisense oligomer, effectively induced exon-skipping in the cardiac and skeletal muscles and rejuvenated the muscle function as supported by demonstration of restored Dystrophin protein production in the heart, diaphragm and limb muscles in mdx mice. The exon skipping effect is dose-dependent and persists for more than 13 weeks after a single injection. Repeated VMO23 treatment in mdx mice restored muscle function to near normal levels as measured by increased force production of limb and respiratory muscles and reduced serum creatine kinase level, indicative of leakiness of cell membrane. No detectable toxicity at the effective dose regime was observed. Thus, delivery-enhanced Vivo-Morpholinos represent a possible treatment for DMD patients |
| Key words:
Duchenne muscular dystrophy(DMD), Vivo Morpholino oligo, Dystrophin, muscle force production |
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