Therapeutic splice modification

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

http://www.ncbi.nlm.nih.gov/pubmed/19125639
http://www.liebertonline.com/doi/pdfplus/10.1089/oli.2008.0161

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 ß-globin (ß-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).