Antisense oligonucleotide Gene therapy study
- Exon Skipping in mdx52 mouse brain
Airmeith Bioscience can help design and/or implement your research projects on disease models. Previously, in partnership with our colleagues in the EU Horizon 2020 BIND consortium (https://bindproject.eu/), we have been examining gene therapy antisense oligonucleotides in the treatment of central nervous system deficits in Duchenne’s muscular dystrophy (Dmd). This genetic disorder is caused by mutations to the Dmd gene on the X chromosome, leading to progressive muscle degeneration, weakness and in some cases, deficits in learning, memory and mental health.
The mdx52 transgenic model contains a neomycin cassette in place of exon 52 in the Dmd gene, disrupting the reading frame of two dystrophin isoforms, Dp427 and Dp140. Antisense oligonucleotides to exon 51 cause skipping and restoration of the reading frame thereby allowing Dp427 expression.
The skipping efficiency and biodistribution of different ASO chemistries was examined by two administration routes to the CNS, to the lateral ventricles and to the subarachnoid space at the cisterna magna. Along with our partners in Transpharmation Ireland, the motor and behavioral phenotypes of the treated mice were also examined to elucidate if treatment can ameliorate CNS symptoms of Duchenne's muscular dystrophy.
Saoudi, A.; Fergus, C.; Gileadi, T.; Montanaro, F.;Morgan, J.; Kelly, V.P.; Tensorer, T.; Garcia, L.; Vaillend, C.; Muntoni, F.; et al. Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models. Cells 2023, 12, 908. https://doi.org/10.3390/cells12060908