Muscular dystrophy is a group of genetic disorders characterised by degeneration of muscles. Different forms of muscular dystrophy can show varying phenotypes with a wide range of age, severity and location of muscle deterioration. Many palliative care options are available for muscular dystrophy patients, but no curative treatment is available. Exon-skipping therapy aims to induce skipping of exons with disease-causing mutations and/or nearby exons to restore the reading frame, which results in an internally truncated, partially functional protein. In antisense-mediated exon-skipping synthetic antisense oligonucleotide binds to pre-mRNA to induce exon skipping. Recent advances in exon skipping have yielded promising results; the US Food and Drug Administration (FDA) approved eteplirsen (Exondys51) as the first exon-skipping drug for the treatment of Duchenne muscular dystrophy, and in vivo exon skipping has been demonstrated in animal models of dysferlinopathy, limb-girdle muscular dystrophy type 2C and congenital muscular dystrophy type 1A. Novel methods that induce exon skipping utilizing Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are also being developed where splice site mutations are created within the genome to induce exon skipping. Challenges remain as exon-skipping agents can have deleterious non-specific effects and different in-frame deletions show phenotypic variance. This article reviews the state of the art of exon skipping for treating muscular dystrophy and discusses challenges and future prospects.

Here we report the entire cDNA sequences for equine αS1-, β- and κ-casein. Based on interspecies comparison, nine exons were found in equine β-casein and five in κ-casein. In equine αS1-casein cDNA the exon 5 was missing, which resulted in the total of 18 exons instead of 19 theoretically possible exons in αS1-casein cDNA. Comparison of DNA sequences representing exon 5 in other species with corresponding equine genomic region confirmed the presence of cryptic exon in horse genomic DNA. Equine αS1-casein mRNA was present in three forms in the lactating mammary gland and we showed that the two shorter forms were produced by skipping either the exon 8 or exon 15. In horse, as in some other mammals, β- and κ-casein are considerably more conserved (sequence identity 53% to 59% and 57% to 67%, respectively) than αS1-casein which appears as the most variable casein among species (sequence identity 40% to 54%). Interestingly, horse caseins resemble human much more than bovine caseins which may also explain the high dietetic value of mares' milk.