ArticleMolecular therapy. Nucleic acids2016
Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing.
Article in Molecular therapy. Nucleic acids, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- RNA exon editing: Splicing the way to treat human diseases.Molecular therapy. Nucleic acids · 2024Review
- Benefits of therapy by dynamin-2-mutant-specific silencing are maintained with time in a mouse model of dominant centronuclear myopathy.Molecular therapy. Nucleic acids · 2022Article
- Evaluating a Targeted Cancer Therapy Approach Mediated by RNAInternational journal of molecular sciences · 2022Article
- Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.International journal of molecular sciences · 2021Review
- Allele-Specific CRISPR/Cas9 Correction of a Heterozygous DNM2 Mutation Rescues Centronuclear Myopathy Cell Phenotypes.Molecular therapy. Nucleic acids · 2019Article
- Efficient system for upstream mRNA trans-splicing to generate covalent, head-to-tail, protein multimers.Scientific reports · 2019Article
- Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA.Molecular therapy. Nucleic acids · 2018Article
- Allele-specific silencing therapy for Dynamin 2-related dominant centronuclear myopathy.EMBO molecular medicine · 2018Article
- Recent advances in understanding congenital myopathies.F1000Research · 2018Review
- Centronuclear myopathies under attack: A plethora of therapeutic targets.Journal of neuromuscular diseases · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 to develop therapeutic strategy, we evaluated here the potential of Spliceosome-Mediated RNA Trans-splicing technology to reprogram the Dnm2-mRNA in vitro and in vivo in mice. We show that classical 3'-trans-splicing strategy cannot be considered as accurate therapeutic strategy regarding toxicity of the pre-trans-splicing molecules leading to low rate of trans-splicing in vivo. Thus, we tested alternative strategies devoted to prevent this toxicity and enhance frequency of trans-splicing events. We succeeded to overcome the toxicity through a 5'-trans-splicing strategy which also allows detection of trans-splicing events at mRNA and protein levels in vitro and in vivo. These results suggest that the Spliceosome-Mediated RNA Trans-splicing strategy may be used to reprogram mutated Dnm2-mRNA but highlight the potential toxicity linked to the molecular tools which have to be carefully investigated during preclinical development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.