BACKGROUND: Antisense-mediated exon skipping is currently one of the most 
promising therapeutic approaches for Duchenne muscular dystrophy (DMD). Using 
antisense oligonucleotides (AONs) targeting specific exons the DMD reading frame 
is restored and partially functional dystrophins are produced. Following proof 
of concept in cultured muscle cells from patients with various deletions and 
point mutations, we now focus on single and multiple exon duplications. These 
mutations are in principle ideal targets for this approach since the specific 
skipping of duplicated exons would generate original, full-length transcripts.
METHODS: Cultured muscle cells from DMD patients carrying duplications were 
transfected with AONs targeting the duplicated exons, and the dystrophin RNA and 
protein were analyzed.
RESULTS: For two brothers with an exon 44 duplication, skipping was, even at 
suboptimal transfection conditions, so efficient that both exons 44 were 
skipped, thus generating, once more, an out-of-frame transcript. In such cases, 
one may resort to multi-exon skipping to restore the reading frame, as is shown 
here by inducing skipping of exon 43 and both exons 44. By contrast, in cells 
from a patient with an exon 45 duplication we were able to induce single exon 45 
skipping, which allowed restoration of wild type dystrophin. The correction of a 
larger duplication (involving exons 52 to 62), by combinations of AONs targeting 
the outer exons, appeared problematic due to inefficient skipping and 
mistargeting of original instead of duplicated exons.
CONCLUSION: The correction of DMD duplications by exon skipping depends on the 
specific exons targeted. Its options vary from the ideal one, restoring for the 
first time the true, wild type dystrophin, to requiring more 'classical' 
skipping strategies, while the correction of multi-exon deletions may need the 
design of tailored approaches.