Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing

@article{Trochet2016ReprogrammingTD,
  title={Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing},
  author={Delphine Trochet and Bernard Prudhon and Arnaud Jollet and Stéphanie Lorain and Marc Bitoun},
  journal={Molecular Therapy. Nucleic Acids},
  year={2016},
  volume={5}
}
Dynamin 2 (DNM2) is a large GTPase, ubiquitously expressed, involved in membrane trafficking and regulation of actin and microtubule cytoskeletons. DNM2 mutations cause autosomal dominant centronuclear myopathy which is a rare congenital myopathy characterized by skeletal muscle weakness and histopathological features including nuclear centralization in absence of regeneration. No curative treatment is currently available for the DNM2-related autosomal dominant centronuclear myopathy. In order… 
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Background Citations
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Methods Citations
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9 Citations

Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA

Benefits of therapy by dynamin-2-mutant-specific silencing are maintained with time in a mouse model of dominant centronuclear myopathy

Physiological impact and disease reversion for the severe form of centronuclear myopathy linked to dynamin

This study highlights an efficient approach to revert the severe form of dynamin-related centronuclear myopathy and reveals that the dynamin conformational switch is key for muscle function and should be targeted for future therapeutic developments.

Efficient system for upstream mRNA trans-splicing to generate covalent, head-to-tail, protein multimers

This plasmid-based trans-splicing system is adaptable to multiple gene delivery systems, and it presents new opportunities for investigating molecular mechanisms of trans- Splicing, generating covalent protein multimers with novel functions within cells, and producing mRNAs encoding large proteins from split precursors.

Allele‐specific silencing therapy for Dynamin 2‐related dominant centronuclear myopathy

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.

Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances

The contribution of the different CNM models to understanding physiopathology and therapy development is reviewed with a focus on the commonly dysregulated pathways and current therapeutic targets.

Centronuclear myopathies under attack: A plethora of therapeutic targets

Different therapeutic strategies that have been tested so far for centronuclear myopathies are reviewed, some of which may be translated to patients.

Recent advances in understanding congenital myopathies

Significant progress in the provision of molecular diagnoses brings important information and value to patients and their families, such as possible disease prognosis, better disease management, and informed reproductive choice.

Allele-Specific CRISPR/Cas9 Correction of a Heterozygous DNM2 Mutation Rescues Centronuclear Myopathy Cell Phenotypes

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