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Exon-skipping oligonucleotides are a well-researched therapeutic strategy for Duchenne's muscular dystrophy (DMD). Despite remarkable successes in animal models with intramuscular and intravenous delivery of unmodified oligonucleotides, the ability to specifically target both normal and dystrophic muscle with a simple peptide ligand could decrease the therapeutic dose required and reduce the potential for toxicity. Thus, 3 rounds of in vivo phage display utilizing a 12-mer peptide library were performed with mdx mice and a peptide motif with potential for targeting to muscle but not liver was identified. This motif was shown to have enhanced binding affinity to C2C12 myoblasts over a scrambled control peptide and in vivo application of a fluorescein-labeled peptide containing the identified motif resulted in increased specificity for the heart and quadriceps muscle after tail-vein administration in C57BL/6 mice. This work has many potential applications for oligonucleotide or drug delivery to muscle for myopathies.

Original publication

DOI

10.1016/j.peptides.2010.06.036

Type

Journal article

Journal

Peptides

Publication Date

10/2010

Volume

31

Pages

1873 - 1877

Keywords

Amino Acid Sequence, Animals, Cell Line, Fluorescein, Fluorescent Dyes, Mice, Mice, Inbred C57BL, Mice, Inbred mdx, Molecular Sequence Data, Muscle, Skeletal, Muscular Dystrophy, Duchenne, Myoblasts, Myocardium, Peptides, Protein Binding