Therapeutic splice modification

[Jon Moulton]

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

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[Only registered users see links. ]

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).