Ruepp, Marc-David (11 June 2013). Combined systemic and local morpholino treatment rescues the phenotype of the SMA Delta 7 mouse model (Unpublished). In: 18th International Annual Meeting of the RNA Society. Davos, CH. 11.-15.06.2013.
Spinal muscular atrophy (SMA) is a childhood fatal motor neuron disease caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, currently without effective treatment. One possible therapeutic approach is the use of antisense oligonucleotides (ASOs) to redirect the splicing of a paralogous gene, SMN2, to increase the production of functional SMN protein. A range of ASOs with different chemical properties is suitable for these applications, including a morpholino (MO) variant, which has a particularly excellent safety, and efficacy profile. We used a 25- nt MO oligomer sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D(-10-34)) with superior efficacy to previously described sequences also in transgenic SMA Δ7 mice. The combined local and systemic administration of MO (bare or conjugated to octa-guanidine) is necessary to increase full-length SMN expression, leading to robust neuropathological features improvement and survival rescue. Additionally, several snRNA levels that are dysregulated in SMA mice could be restored by MO treatment. These results demonstrate that MO therapy is efficacious and can result in phenotypic rescue. These data provide important insights for the development of therapeutic strategies in SMA patients.
Item Type: |
Conference or Workshop Item (Poster) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
UniBE Contributor: |
Ruepp, Marc-David |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
Language: |
English |
Submitter: |
Christina Schüpbach |
Date Deposited: |
05 Aug 2014 14:01 |
Last Modified: |
05 Dec 2022 14:36 |
URI: |
https://boris.unibe.ch/id/eprint/57529 |
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