The US Food and Drug Administration today (19 Sep 2016) granted Accelerated Approval to eteplirsen (EXONDYS 51), a Morpholino oligo-based treatment for some forms of Duchenne muscular dystrophy (DMD). This is the first approval of a Morpholino drug.
DMD, a devastating childhood disease that is usually fatal within the first 20 years of life, is caused when the protein dystrophin is not produced. Eteplirsen is a Morpholino antisense oligo targeting exon 51 of the DMD transcript to cause its excision from the DMD pre-mRNA. Some mutations causing DMD are frameshift mutation (often deletions) occurring adjacent to exon 51; for some of these, skipping exon 51 can restore the reading frame of the functional dystrophin protein and cause some internally-truncated dystrophin to be made.
Eteplirsen (sequence source: US FDA ETEPLIRSEN BRIEFING DOCUMENT NDA 206488)
Morpholino phosphorodiamidate antisense oligomer
Predicted Tm: 88.9°C at 10 µM oligo.
DMD-001 Exon 51, ENST00000357033.8 in Ensembl.org, RNA target site marked. Given that the target site is within an exon, this is likely blocking binding of an exonic splice enhancer protein and so altering splicing by interfering with splice regulation.