| First Author | Trochet D | Year | 2018 |
| Journal | EMBO Mol Med | Volume | 10 |
| Issue | 2 | Pages | 239-253 |
| PubMed ID | 29246969 | Mgi Jnum | J:261350 |
| Mgi Id | MGI:6155312 | Doi | 10.15252/emmm.201707988 |
| Citation | Trochet D, et al. (2018) Allele-specific silencing therapy for Dynamin 2-related dominant centronuclear myopathy. EMBO Mol Med 10(2):239-253 |
| abstractText | Rapid advances in allele-specific silencing by RNA interference established a strategy of choice to cure dominant inherited diseases by targeting mutant alleles. We used this strategy for autosomal-dominant centronuclear myopathy (CNM), a rare neuromuscular disorder without available treatment due to heterozygous mutations in the DNM2 gene encoding Dynamin 2. Allele-specific siRNA sequences were developed in order to specifically knock down the human and murine DNM2-mRNA harbouring the p.R465W mutation without affecting the wild-type allele. Functional restoration was achieved in muscle from a knock-in mouse model and in patient-derived fibroblasts, both expressing the most frequently encountered mutation in patients. Restoring either muscle force in a CNM mouse model or DNM2 function in patient-derived cells is an essential breakthrough towards future gene-based therapy for dominant centronuclear myopathy. |
