Therapeutic splice modification

Jon Moulton

Registered Senior Member
Bauman J, Jearawiriyapaisarn N, Kole R. Therapeutic Potential of Splice-Switching Oligonucleotides. Oligonucleotides. 2009 Jan 6. [Epub ahead of print]

You can get the full text from the publisher for free, it's online but this message board won't allow me to post the URL. Try Googling the title.

Ryszard Kole of AVI BioPharma Inc. has published this review of therapeutic applications of splice-modifying oligos, including information about Morpholinos targeting Duchenne muscular dystrophy.

In particular he writes that the PPMO-B, a Morpholino conjugated with a cell-penetrating peptide, enters many muscles and in particular the heart where it produces 20%–30% of normal Dystrophin.

"Exon 23–skipped mRNA and restored production of dystrophin protein remained detectable for at least 2–3 months after treatment, especially in diaphragm and quadriceps, where 100% exon skipping was maintained. This suggested that the PPMO-B/ PMO is very stable in muscle tissues, because the half-life of dystrophin mRNA is only ~16 hours (Tennyson et al., 1996)."

This review explores a number of other potential therapeutic applications of splice-modifying Morpholinos, including discussions of targets such as β-globin (β-Thalassemia), SMN2 (Spinal muscular atrophy), TNFR2 and MyD88 (Inflammatory diseases), HER2 (Cancer), ClC-1 (Dystrophia myotonica type 1), ATP7A (Menkes disease), ATM (Ataxia telangiectasia), APOB (Atherosclerosis), PCCA, PCCB, and MUT (Propionic and methylmalonic acidemias).