Journal article
Targeted SMN exon skipping: A useful control to assess in vitro and in vivo splice-switching studies
Biomedicines, Vol.9(5), Article 552
2021
Abstract
The literature surrounding the use of antisense oligonucleotides continues to grow, with new disease and mechanistic applications constantly evolving. Furthermore, the discovery and advancement of novel chemistries continues to improve antisense delivery, stability and effectiveness. For each new application, a rational sequence design is recommended for each oligomer, as is chemistry and delivery optimization. To confirm oligomer delivery and antisense activity, a positive control AO sequence with well characterized target-specific effects is recommended. Here, we describe splice-switching antisense oligomer sequences targeting the ubiquitously expressed human and mouse SMN and Smn genes for use as control AOs for this purpose. We report two AO sequences that induce targeted skipping of SMN1/SMN2 exon 7 and two sequences targeting the Smn gene, that induce skipping of exon 5 and exon 7. These antisense sequences proved effective in inducing alternative splicing in both in vitro and in vivo models and are therefore broadly applicable as controls. Not surprisingly, we discovered a number of differences in efficiency of exon removal between the two species, further highlighting the differences in splice regulation between species.
Details
- Title
- Targeted SMN exon skipping: A useful control to assess in vitro and in vivo splice-switching studies
- Authors/Creators
- L.L. Flynn (Author/Creator) - Murdoch UniversityC. Mitrpant (Author/Creator) - Perron Institute for Neurological and Translational ScienceA. Adams (Author/Creator) - Murdoch UniversityI.L. Pitout (Author/Creator) - Murdoch UniversityA. Stirnweiss (Author/Creator) - PYC Therapeutics (Australia)S. Fletcher (Author/Creator) - Murdoch UniversityS.D. Wilton (Author/Creator) - Murdoch University
- Publication Details
- Biomedicines, Vol.9(5), Article 552
- Publisher
- MDPI
- Identifiers
- 991005543443307891
- Copyright
- © 2021 by the authors
- Murdoch Affiliation
- Health Futures Institute; Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
31 File views/ downloads
97 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.255 Musculoskeletal Disorders
- 1.255.628 Duchenne Muscular Dystrophy
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Medicine, Research & Experimental
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology