Journal article
Cell-penetrating peptide–morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo
Biochemical Society Transactions, Vol.35(4), pp.826-828
2007
Abstract
The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)4AhxB (Ahx is 6-aminohexanoic acid and B is β-alanine) CPP–PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)4AhxB–PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)4AhxB–PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)4AhxB–PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R9F2 CPP significantly decreased the efficacy of the resulting PPMO (CPP–PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.
Details
- Title
- Cell-penetrating peptide–morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo
- Authors/Creators
- S. Fletcher (Author/Creator)H.M. Moulton (Author/Creator)B.W. Neuman (Author/Creator)G. McClorey (Author/Creator)D.A. Stein (Author/Creator)S. Abes (Author/Creator)S.D. Wilton (Author/Creator)M.J. Buchmeier (Author/Creator)B. Lebleu (Author/Creator)P.L. Iversen (Author/Creator)
- Publication Details
- Biochemical Society Transactions, Vol.35(4), pp.826-828
- Publisher
- Portland Press
- Identifiers
- 991005542061907891
- Copyright
- 2007 Biochemical Society
- Murdoch Affiliation
- Murdoch University
- 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
43 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
- ESI research areas
- Biology & Biochemistry